Study to Assess Effectiveness and Safety of Zanubrutinib for Patients with Marginal Zone Lymphoma Treated in Italy Under the Named Patient Program (NPP)
An Italian Multicenter Retrospective Observational Study to Assess Effectiveness and Safety of Zanubrutinib for Patients with Marginal Zone Lymphoma Treated in Italy Under the Named Patient Program (NPP)
Теги: #Relapsed|Refractory
Локации: AO di Cosenza, P.O. "Annunziata" - UOC di Ematologia; Cosenza; Italy,AOU Città della Salute e della Scienza, "Le Molinette" - Divisione di Ematologia; Torino; Italy,AOU di Ferrara_ UO di Ematologia - Dipartimento di Oncologia e Medicine Specialistiche; Ferrara; Italy,AOU SS Antonio e Biagio e Cesare Arrigo; Alessandria; Italy,ASST Grande Ospedale Metropolitano Niguarda _ UOC Ematologia; Milano; Italy,Azienda sanitaria universitaria Giuliano Isontina (ASU GI) - Ospedale Maggiore- SC (UCO) Ematologia; Trieste; Italy,Fondazione PTV Policlinico Tor Vergata- U.O.C. Patologie Linfoproliferative; Roma; Italy,IOV - Istituto Oncologico Veneto - IRCCS _UOC Oncologia1; Padova; Italy,IRCCS-AOU di Bologna; Bologna; Italy,Istituto Clinico Humanitas IRCCS - UO Ematologia; Milano; Italy,Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST IRCCS; Meldola; Forlì Cesena; Italy,Ospedale Ca` Foncello, Azienda ULSS n. 2 Marca trevigiana - UOC Ematologia Dipartimento di Medicina; Treviso; Italy,Ospedale Santa Maria d
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Описание
Observational, non-interventional, retrospective, multicentre study focusing on efficacy and safety of zanubrutinib in daily clinical practice in patients with relapsed/refractory (R/R) marginal zone lymphoma.
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Критерии включения
1. Histologically confirmed diagnosis of relapsed/refractory marginal zone lymphoma
2. Patients who received at least one dose of zanubrutinib under the Named patient program (D.M. 7 Sep 2017), between January 2021 and October 2023 3) Age≥18 at start of zanubrutinib therapy. 4) Signature of written informed consent to study participation and personal data processing.
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Критерии исключения
1) relapsed/refractory marginal zone lymphoma patients who received zanubrutinib in a clinical trial context.
Pirtobrutinib in Combination With Rituximab in Newly Diagnosed Marginal Zone Lymphoma (R+Pirto in Newly Diagnosed MZL)
A Phase II Study of Pirtobrutinib in Combination With Rituximab in Newly Diagnosed Marginal Zone Lymphoma: A Risk Adapted Approach
Теги: #Relapsed|Refractory
Локации: Huntsman Cancer Institute at University of Utah; Salt Lake City; Utah; United States
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Описание
The purpose of this clinical trial is to learn if the drugs Pirtobrutinib and Rituximab are effective for the treatment of newly diagnosed marginal zone lymphoma.
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Критерии включения
* Subjects aged ≥ 18 years.
* ECOG Performance Status ≤ 2.
* Histologically confirmed marginal zone lymphoma, including splenic, nodal, and extranodal sub-types per the enrolling institution.
* Subjects must have an indication for treatment.
* No prior systemic therapy for MZL except for the following:
* Prior antibiotic therapy for H. pylori, C. psittaci, and B. burgdorferi
* Prior antiviral therapy for HCV
---Note: Subjects are eligible if they had a prior splenectomy or other local surgical treatment or local radiation therapy without systemic therapy and now require their first ever systemic therapy. In the event of the receipt of radiation therapy, the minimum washout period is 14 days
* Subjects with gastric MALT lymphoma must be H. pylori negative or have failed a trial of H. pylori eradication
* Subjects with localized MALT lymphoma must be ineligible for, have refused or failed radiation therapy (washout period of 14 days)
* Adequate organ function as defined as:
* Hematologic:
* Absolute neutrophil count ≥ 750 cells/mm3 (≥ 0.75 x 10/^9/L) independent of G-CSF support, unless there is documented bone marrow involvement or splenomegaly with ensuing cytopenia in which case ANC of 500 cells/mm3 (0.5 x 10/^9/L) is permissible. Also, there should be no evidence of myelodysplasia or hypoplastic bone marrow
* Platelet count ≥ 50,000/mm3 (≥50 x 10/^9/L) independent of transfusion support unless there is documented bone marrow involvement in which case platelet count of ≥30,000 cells/mm3 (≥30 x 10/^9/L) is permissible. Subjects must be responsive to transfusion support if given for thrombocytopenia and subjects refractory to transfusion support are not eligible. Also, there should be no evidence of myelodysplasia or hypoplastic bone marrow.
* Note: The platelet count threshold in the current study (≥50,000 cells/mm/^3 or ≥50 x 10/^9/L) is lower than normal threshold (≥75,000 cells/mm/^3 or ≥75 x 10/^9/L) as the majority of MZL subjects have lower than normal platelets due to splenomegaly and or autoimmune phenomena (which are related to the underlying lymphoma) and hence the lower than normal platelet count threshold for study entry
* Hemoglobin ≥ 8 g/dL independent of transfusion support unless there is documented bone marrow involvement or splenomegaly with ensuing cytopenia in which case hemoglobin of ≥7 g/dL (≥70 g/L) is permissible. Subjects must be responsive to transfusion support if given for anemia and subjects refractory to transfusion support are not eligible. Also, there should be no evidence of myelodysplasia or hypoplastic bone marrow.
* Hepatic:
----Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
-----Subjects with liver involvement will be allowed to enroll with total bilirubin ≤3 x ULN
* AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN ----Subjects with liver metastases will be allowed to enroll with AST and ALT levels ≤ 5 x ULN.
* Life expectancy of />3 months, in the opinion of the investigator
* For female subjects: Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
* Women /< 50 years of age:
---Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and
* Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or
* Underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
* Women ≥ 50 years of age:
* Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or
* Had radiation-induced menopause with last menses />1 year ago; or
* Had chemotherapy-induced menopause with last menses />1 year ago; or
* Underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
* Female subjects of childbearing potential and male subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception as described in Section 5.3.1.
* Subjects may not plan to become pregnant or breastfeed within 1 month of the last dose of pirtobrutinib or 12 months following the last rituximab infusion
* Ability to swallow oral tablets.
* Subjects or their legal representatives must be able to read, understand, and provide informed consent to participate in the trial.
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Критерии исключения
* Subjects requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist.
* Receipt of live-virus vaccines within 28 days prior to the initiation of study treatment or need for live-virus vaccines at any time during study treatment
* Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of the study drug.
* History of bleeding diathesis
* Major surgery 4 weeks prior to starting study drug or who have not fully recovered from major surgery.
* The diagnosis of another malignancy which is, in the opinion of the investigator, likely to negatively impact study participation or subject safety.
* Subjects with CNS involvement
* Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
* Cardiovascular disorders:
* Grade 3 NYHA functional classification system of heart failure, uncontrolled or symptomatic arrhythmias ---Unstable angina pectoris or acute coronary syndrome within 2 months of first dose.
---History of myocardial infarction within 3 months prior to the first dose of study treatment
---Stroke or intracranial hemorrhage within 6 months prior to the first dose of study treatment.
* QTc prolongation defined as a QTcF /> 470 ms. ----Correction of suspected drug induced QTcF prolongation can be attempted at the investigator`s discretion and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation.
* Correction for underlying bundle branch block (BBB) allowed .
* Left ventricular ejection fraction /< 40% within 12 months prior to the first dose of study treatment.
* Note: Subjects with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker
* Any other condition that would, in the Investigator`s judgment, contraindicate the subject`s participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, /[subjects may not receive the drug through a feeding tube/], etc.)
* Known HIV infection.
* Active hepatitis B (known positive HBV surface antigen (HBsAg) result), or hepatitis C.
* Note: Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody /[anti-HBc/] and absence of HBsAg) are eligible, if HBV DNA PCR is negative. Subjects with positive anti-HBc and negative HBV DNA should be on prophylactic nucleo(t)side analogue therapy to prevent reactivation with serial HBV DNA PCR monitoring per section 6.6.9.
Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
* Known active cytomegalovirus (CMV) infection
* Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia /[AIHA/], idiopathic thrombocytopenic purpura /[ITP/]) for which new therapy was introduced or existing therapy was escalated within the 4 weeks prior to study enrollment to maintain adequate blood counts
* Medical, psychiatric, cognitive, or other conditions that may compromise the subject`s ability to understand the subject information, give informed consent, comply with the study protocol or complete the study.
* Known prior severe hypersensitivity to investigational product (IP) or any component in its formulations (NCI CTCAE v5.0 Grade ≥ 3).
Mosunetuzumab in Patients With Newly Diagnosed Extranodal Marginal Zone Lymphoma
Phase II Trial of Mosunetuzumab in Patients With Newly Diagnosed Extranodal Marginal Zone Lymphoma (EMZL) (ML44933)
Теги: #Relapsed|Refractory
Локации: University of Miami; Miami; Florida; United States
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Описание
The purpose of this study is to test a new medication called Mosunetuzumab to see if it can help people with Extranodal Marginal Zone Lymphoma (EMZL). This study will include people who have not yet received any treatment for cancer and whose cancer is in stage I-IV. This study will help doctors understand if Mosunetuzumab improves outcomes in people with EMZL and if it is safe to use.
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Критерии включения
1. Men and women aged 18 years or older at the time of signing informed consent.
2. Able and willing to sign the informed consent form (ICF).
3. Ability to comply with the trial protocol.
4. Histologically confirmed EMZL presenting with stage I-IV disease.
5. Previously untreated participants.
1. Participants with H. pylori-positive gastric EMZL who received an initial treatment with currently accepted antibiotics may be considered eligible if, after antibiotic regimen, participant has histologically confirmed MZL.
2. Participants who were previously treated with localized therapy (eg, radiation or surgery) and never received systemic therapy and present with recurrent disease are eligible upon histological confirmation of MZL.
6. Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥1 lesion that measures />1.5 cm in the longest diameter (LDi) and ≥1.0 cm in the longest perpendicular diameter as assessed by CT or MRI, especially in extranodal sites, per response criteria for lymphomas (Cheson, et al., 2014). Imaging must be conducted within 6 weeks prior to the start of therapy.
1. Participants with skin EMZL who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that skin lesion measures ≥1.5 cm in diameter by tape measure and is documented by photo or there are multiple skin lesions measuring />1 cm in diameter on the body and at least one of them is histologically confirmed as EMZL.
2. Participants with gastric EMZL histologically confirmed and need therapy but do not have measurable disease and in which response to treatment can be assessed by multiple random gastric biopsies per Groupe d`Etude des Lymphomes de l`Adult (GELA) criteria (Ruskoné Fourmestraux, et al., 2011).
3. Participants with conjunctival EMZL who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that conjunctival lesion measures ≥1 cm in diameter by tape measure and is documented by photo or there are multiple conjunctival lesions measuring together />1.5 cm. At least one of the lesions needs be histologically confirmed as EMZL.
7. Participants must be willing to provide tissue biopsy from the most recent available archival tissue or undergo an incisional or excisional lymph node or tissue biopsy. If biopsy can be reviewed to confirm the diagnosis but there is no extra tissue for exploratory studies, such participants can still be enrolled in this trial.
8. Participant should have at least one of the following criteria for treatment initiation:
* Threatened extranodal organ function
* Involvement of ≥3 nodal sites, each with diameter of ≥3 cm
* Any nodal or extranodal tumor mass with a diameter of ≥5 cm
* B symptoms (fever ≥38 degrees Celsius of unclear etiology, night sweats, weight loss />10% within the prior 6 months) or other symptoms attributed to disease or specific organ involvement associated with the relapse.
* Risk of local compressive symptoms that may result in organ compromise
* Splenomegaly or splenic lesion without splenomegaly
* Leukopenia attributed to MZL (leukocytes /<1000/mm3)
* Leukemia (/>5,000 lymphoma cells/mm3)
* Requirement for transfusion or growth factor support attributed to lymphoma
* Involvement of 2 or more extranodal sites, with tumor/lesion in each extranodal site ≥1 cm
9. Life expectancy />3 months.
10. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
11. Adequate hematologic, hepatic, and renal function tested within 6 weeks prior to the start of therapy (values must not be achieved with growth factors):
* Absolute neutrophil count (ANC) ≥1.0 × 10/^9/L.
* Hemoglobin ≥8.0 g/dL.
* Platelet count ≥ 75 × 10/^9/L.
* Total bilirubin ≤1.5 × upper limit normal (ULN). Participants with documented history of Gilbert`s syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible.
* Alanine transaminase (ALT)/aspartate aminotransferase (AST) ≤3.0 × ULN or ≤5 × ULN in the presence of liver involvement by lymphoma.
* Creatinine within normal institutional limits, or
* calculated creatinine clearance ≥30 mL/min/1.73 m2 using the Modification of Diet in Renal Disease formula
* calculated creatinine clearance ≥35 mL/min by the Cockcroft-Gault Equation (Cockcroft, 1976)
* estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 using the Modification of Diet in Renal Disease formula for participants with creatinine levels above institutional normal (unless due to lymphoma)
12. Willingness to avoid pregnancy during the trial and for at least 90 days after the last dose of the trial intervention.
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Критерии исключения
1. Evidence of diffuse large B cell lymphoma (DLBCL) transformation. Participants with presumptive evidence of transformation based on clinical assessment of factors such as, but not limited to, increasing lactate dehydrogenase, rapidly worsening disease, or frequent B-symptoms, must be ruled out for a transformation to a more aggressive disease, such as DLBCL.
2. History of central nervous system lymphoma (either primary or metastatic) or leptomeningeal disease. Participants with Dural MZL are eligible.
3. Patients that need immediate cytoreduction.
4. Concurrent or previous anticancer therapy (eg, chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor embolization).
5. Treatment with systemic immunosuppressive medications, including, but not limited to, prednisone (/>20 mg), azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1.
1. Steroids that are used for treatment of allergy or other underlying condition are permittable, but not steroids started to treat lymphoma. Participants receiving corticosteroids must be at a dose level ≤20 mg/day within 7 days of the trial intervention administration.
2. The use of inhaled corticosteroids is permitted
3. The use of mineralocorticoids for management of orthostatic hypotension is permitted
4. Single dose of dexamethasone for nausea or B symptoms is permitted
5. Antibiotic treatment of H. pylori-positive gastric EMZL
6. Allogeneic stem cell transplant, or autologous stem cell transplant or Chimeric antigen receptor T-cell therapy for any indication
7. Active graft versus host disease.
8. Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.
9. Current or previous other malignancy within 3 years of trial entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy.
10. Significant concurrent, uncontrolled medical condition, including, but not limited to, renal, hepatic, hematological, gastrointestinal (GI), endocrine, pulmonary, neurological, cerebral, or psychiatric disease.
11. Chronic or current active infectious disease (including severe acute respiratory syndrome (SARS) coronavirus 2 (CoV-2)) requiring systemic antibiotics, antifungal, or antiviral treatment or any major episode of infection requiring treatment with IV antibiotics within 4 weeks of Day 1 of Cycle 1
12. Exposure to a live vaccine within 30 days of administration or anticipation that a live attenuated vaccine will be required during the study.
1. Inactivated influenza vaccinations may be given during the influenza season.
2. An approved coronavirus disease 2019 (COVID-19) vaccine (messenger ribonucleic acid (mRNA), inactivated virus, and replication deficient viral vector vaccines) is allowed.
13. Known human immunodeficiency virus (HIV) infection or positivity on immunoassay. Note: HIV screening test is optional
14. History of solid organ transplantation
15. History of severe allergic or anaphylactic reaction to humanized, chimeric or murine monoclonal antibodies (MAbs)
16. Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary (CHO) cells or any component of the mosunetuzumab, lenalidomide, or thalidomide formulation, including mannitol.
17. Significant cardiovascular disease (eg, New York Heart Association Class III or IV cardiac disease, myocardial infarction within the previous 3 months, unstable arrhythmia, or unstable angina) or significant pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm)
18. Known or suspected chronic active Epstein-Barr virus (EBV) infection
19. Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
20. History of progressive multifocal leukoencephalopathy (PML)
21. Active hepatitis B infection
a. Patients who are hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (HBcAb) positive, must be negative for hepatitis B virus (HBV) polymerase chain reaction (PCR) to be eligible for study participation
22. Active hepatitis C infection
a. Patients who are positive for hepatitis C virus (HCV) antibody must be negative for HCV by PCR to be eligible for study participation
23. History of autoimmune disease, including, but not limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener`s granulomatosis, Sjögren`s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
1. Patients with a remote history of, or well-controlled, autoimmune disease with a treatment free interval from immunosuppressive therapy for 12 months may be eligible to enroll if judged to be safe by the investigator
2. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible
3. Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
4. Patients with a history of disease-related immune thrombocytopenic purpura, or autoimmune hemolytic anemia may be eligible
5. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (eg, patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
* i. Rash must cover 10% of body surface area
* ii. Disease is well controlled at baseline and requires only low-potency topical corticosteroids
* iii. No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency oral corticosteroids within the previous 12 months
24. Positive SARS-CoV-2 test within 7 days prior to enrollment. Rapid antigen test result is also acceptable.
Study to Evaluate Adverse Events, Change in Disease Activity, and How Intravenously Infused ABBV-291 Moves Through the Body in Adult Participants With Non-Hodgkin`s Lymphoma
A Phase 1 First-In-Human Study Evaluating Safety, Pharmacokinetics, and Efficacy of ABBV-291 in Non-Hodgkin`s Lymphoma
Теги: #Relapsed|Refractory
Локации: Carolina BioOncology Institute /ID# 265259; Huntersville; North Carolina; United States,Hadassah Medical Center-Hebrew University /ID# 261658; Jerusalem; Yerushalayim; Israel,START Mountain Region /ID# 267592; West Valley City; Utah; United States,Tel Aviv Sourasky Medical Center /ID# 261659; Tel Aviv; Tel-Aviv; Israel,The Cancer Institute Hospital Of JFCR /ID# 267470; Koto-ku; Tokyo; Japan,Virginia Cancer Specialists - Fairfax /ID# 265082; Fairfax; Virginia; United States
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Описание
Non-Hodgkin`s lymphoma (NHL) is a cancer that arises from the transformation of normal B and T lymphocytes (white blood cells). The purpose of this study is to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of ABBV-291 in adult participants in relapsed or refractory (R/R) NHL, including but not limited to diffuse large b-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL). Adverse events will be assessed.
ABBV-291 is an investigational drug being developed for the treatment of NHL. This study will include a dose escalation phase to determine the maximum administered dose (MAD)/Maximum tolerated dose (MTD) of ABBV-291 and a dose expansion/optimization phase to determine the change in disease activity in participants with R/R NHL. Approximately 165 adult participants with multiple NHL subtypes will be enrolled in the study in sites world wide
In the dose escalation phase of the study participants will receive escalating Intravenously (IV) infused doses of ABBV-291, until the MAD/MTD is determined. In the dose expansion/optimization phase of the study participants receive IV infused ABBV-291, as part of the approximately 74 month study duration.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, and side effects.
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Критерии включения
* For dose escalation (Part 1) only: Participants must have documented diagnosis of B-cell malignancies including (but not limited to) the following, with histology based on criteria established by the World Health Organization (WHO), and measurable disease requiring treatment:
* Mantle cell lymphoma (MCL);
* Marginal zone lymphoma (MZL);
* Waldenstrom macroglobulinemia (WM);
* Diffuse large b-cell lymphoma (DLBCL) (including: germinal center B-cell type, activated B-cell type, primary cutaneous DLBCL /[leg type/], Epstein-Barr virus-positive (EBV+) DLBCL /[not otherwise specified/], DLBCL associated with chronic inflammation, human herpesvirus 8-positive /[HHV8+/] DLBCL /[not otherwise specified/], B cell lymphoma /[unclassifiable/] with features intermediate between DLBCL and classical Hodgkin lymphoma, high-grade B-cell lymphoma /[not otherwise specified/], high-grade B-cell lymphoma /[with MYC (avian myelocytomatosis viral oncogene homolog) and BCL2 and/or BCL6 rearrangements/], DLBCL arising from follicular lymphoma /[FL/] /[transformed FL/]);
* FL Grades 1 to 3B;
* For dose expansion (Part 2) only: Participants must have documented diagnosis of one of the following B-cell malignancies, with histology based on criteria established by the WHO, and measurable disease requiring treatment:
* Part 2a only: DLBCL (including: germinal center B-cell type, activated B-cell type, primary cutaneous DLBCL /[leg type/], EBV+ DLBCL /[not otherwise specified/], DLBCL associated with chronic inflammation, HHV8+ DLBCL /[not otherwise specified/], B-cell lymphoma /[unclassifiable/] with features intermediate between DLBCL and classical Hodgkin lymphoma, high-grade B-cell lymphoma /[not otherwise specified/], high-grade B-cell lymphoma /[with MYC and BCL2 and/or BCL6 rearrangements/], DLBCL arising from FL /[transformed FL/]);
* Part 2b only: FL Grades 1 to 3B;
* Part 2c only: Mantle cell lymphoma;
* For all participants (Parts 1 and 2):
* Must be considered relapsed or refractory to, or intolerant of, at least 2 or more prior lines of therapy known to provide a clinical benefit for their condition, and for whom there is no appropriate locally available therapy known to provide clinical benefit (e.g., standard chemotherapy or autologous stem cell transplantation /[ASCT/]).
* Indolent non-Hodkin`s lymphoma (NHL) participants must meet relevant disease specific requirements for treatment (e.g., National Comprehensive Cancer Network /[NCCN/], Groupe d`Etude des Lymphomes Folliculaires /[GELF/]).
* History of allogeneic stem cell transplantation must be stable off of immunosuppression for at least 3 months.
* For participants enrolled in backfill cohorts or at dose levels previously cleared, subjects must provide consent to an on-treatment fresh tumor biopsy from the same tumor lesion as the baseline tumor tissue. This requirement may be waived at the discretion of the contract research organization (CRO) Medical Monitor if collecting a biopsy would place the subject at risk of harm or would require a technically complicated procedure based on tumor location as assessed by the investigator or could hinder a subject`s ability to participate in the study.
* Previously treated with a CD79b-targeting therapy (e.g., CD79b monoclonal antibody) a core or excision tumor biopsy subsequent to the most recent CD79b-targeting therapy must be collected. Tumor biopsy requirements may be modified by Sponsor during the study. This requirement may be waived at the discretion of the contract research organization (CRO) Medical Monitor if collecting a biopsy would place the subject at risk of harm or would require a technically complicated procedure based on tumor location as assessed by the investigator or could hinder a subject`s ability to participate in the study.
* CD79b expression status will be assessed in all participants.
* Have an eastern cooperative oncology group (ECOG) Performance Status of 0 or 1.
* Laboratory values meeting the criteria in the protocol within the screening period prior to the first dose of study drug (if multiple samples are drawn within the screening period, the sample/result immediately prior to Cycle 1 Day 1 is applicable).
* Availability of representative baseline tumor tissue (most recent archived tumor tissue or fresh biopsy collected during screening phase) suitable for immunohistochemistry (IHC) testing. This requirement may be waived at the discretion of the CRO Medical Monitor if collecting a biopsy at screening would place the participant at risk of harm or would require a technically complicated procedure based on tumor location as assessed by the investigator or could hinder a participant`s ability to participate in the study.
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Критерии исключения
* History of interstitial lung disease (ILD) or pneumonitis that required treatment with systemic steroids, or any evidence of active ILD or pneumonitis.
* Treatment with any of the following:
* Anticancer therapy including chemotherapy, radiotherapy, small molecule, investigational, and biologic agents within 14 days (or at least 5 half-lives, whichever is shorter), prior to the first dose of the study treatment;
* CD79b-directed agents (e.g., CD79b monoclonal antibody therapy) within 4 weeks (or at least 5 half-lives, whichever is shorter) prior to the first dose of study treatment.
* Prior treatment with an antibody drug conjugate that consists of a topoisomerase I inhibitor.
Zanubrutinib Plus Rituximab As Front-line Treatment for Mucosa-associated Lymphoid Tissue Lymphoma (MALT)
Zanubrutinib Plus Rituximab As Front-line Treatment for Mucosa-associated Lymphoid Tissue Lymphoma (MALT): a Single-arm, Open-label, Multicenter, Phase II Study(ZAMA)
Теги: #Relapsed|Refractory
Локации: Sun Yat-sen Universitiy Cancer Center, Sun Yat-Sen University; Guangzhou; Guangdong; China
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Описание
This is a prospective, single-arm, multicenter, phase II clinical trial to evaluate the efficacy and safety of Zanubrutinib in combination with Rituximab as a first-line treatment for patients with mucosa-associated lymphoid tissue (MALT) extranodal marginal zone lymphoma.
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Критерии включения
1. Mucosa-associated lymphoid tissue (MALT) extranodal marginal zone lymphoma confirmed by histopathology.
2. Newly diagnosed with Ann Arbor stage III-IV or relapsed MALT after local treatment .
3. No prior systemic anti-lymphoma therapy (except for H. pylori eradication therapy in H. pylori-positive gastric MALT patients).
4. No histopathological transformation to high-grade lymphoma.
5. At least one measurable lesion according to the Lugano 2014 criteria.
7. Age ≥ 18 years, with no gender restrictions. 7. An ECOG performance status score of 0-2. 8. An expected survival time of more than 12 months. 9. Adequate bone marrow, cardiac, pulmonary, liver, and kidney function. 10. Willing to participate in the clinical study; fully informed and aware of the study, having signed the informed consent form; willing and able to comply with all study procedures.
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Критерии исключения
1. Patients with a history of stroke, intracranial hemorrhage, or warfarin use within the past 6 months.
2. Patients with central nervous system involvement.
3. Patients who have undergone allogeneic hematopoietic stem cell transplantation in the past.
4. Patients who have previously used BTK inhibitors or received CD20 monoclonal antibody therapy.
5, Patients with active infections, except for tumor-related B-symptom fever. 6. Patients with a concurrent history of other malignancies, except for cured cervical carcinoma in situ or basal cell carcinoma of the skin.
7. Patients receiving potent cytochrome P450 inhibitors. 8. Patients with severe cardiovascular diseases, such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or a history of myocardial infarction within the past 12 months.
9. Patients, as judged by the investigator, who have significant organ dysfunction or uncontrollable comorbidities that pose a safety risk, or who have absorption and metabolism issues with Zanubrutinib.
10. Pregnant or breastfeeding women and women of childbearing age unwilling to use contraception.
11. Patients who have received anti-tumor therapy within 4 weeks prior to enrollment.
12. Patients with active chronic hepatitis B or active hepatitis C. 13. Patients who have received systemic corticosteroid treatment or other immunosuppressive therapy within 14 days prior to the start of study treatment.
Low Dose Mosunetuzumab for the Treatment of Patients With Indolent B-Cell Lymphoma
Low Dose Mosunetuzumab for Indolent B-Cell Lymphoma
Локации: Fred Hutch/University of Washington Cancer Consortium; Seattle; Washington; United States
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Описание
This phase II trial tests the safety, side effects and effectiveness of mosunetuzumab in treating patients with slow growing (indolent) B-cell lymphoma. Mosunetuzumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread.
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Критерии включения
* 18 years or older at time of signing informed consent
* Capable of understanding and providing written informed consent
* Histologically confirmed indolent B-cell non-Hodgkin lymphoma with no prior therapy for lymphoma. (Prior peptide-based therapeutic vaccines are allowed.) Eligible histologies include:
* Follicular lymphoma (grade 1-2 or 3A)
* Marginal zone lymphoma
* Ann Arbor stage II-IV disease
* No prior therapy for lymphoma
* Have low-tumor burden disease, defined by Groupe D`Etude des Lymphomes Folliculaires (GELF) criteria:
* Nodal or extranodal tumor mass /< 7 cm
* Involvement of less than 3 nodal sites with a diameter /> 3 cm
* No systemic or B symptoms
* No splenomegaly /> 16 cm by imaging
* No local risk of vital organ compression
* No pleural or peritoneal serous effusions
* No leukemic phase (/> 5,0000/ uL circulating lymphocytes)
* No significant cytopenias defined as platelets /< 100,000/uL, hemoglobin /< 10 g/dL, or absolute neutrophil count (ANC) /< 1500/ uL
* Have measurable nodal disease, including at least 1 disease site measuring at least 1.5 cm in longest dimension on CT or fludeoxyglucose F-18 (FDG)-PET, or a FDG-avid extranodal measurable site measuring at least 1.0 cm in longest dimension. Measurable disease also includes spleen size more than 13 cm in vertical length
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Creatinine clearance ≥ 50 mL/min calculated by Cockcroft-Gault equation
* Total bilirubin ≤ 1.5 x the upper limit of normal (ULN), except in patients with Gilbert`s syndrome who may have a total bilirubin up to ≤ 3 x ULN
* Aspartate aminotransferase (AST) ≤ 3 x the ULN
* Alanine aminotransferase (ALT) ≤ 3 x the ULN
* Gamma glutamyl transferase (GGT) ≤ 3 x the ULN
* Negative serum or urine pregnancy test within 7 days of initiating mosunetuzumab for women of childbearing potential, defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year
* Fertile male and woman of childbearing potential must agree to use highly effective contraceptive methods from start of treatment to at least 3 months after the last dose of mosunetuzumab
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Критерии исключения
* History of severe allergic reaction to monoclonal antibody therapy
* History of a second primary malignancy that could affect compliance with the protocol or interpretation of results except with permission of the principal investigator. Malignancies treated curatively or at low-risk of progressing at the judgment of the principal investigator (PI) may be included
* Known active and uncontrolled bacterial, viral, fungal, mycobacterial, or other infection at study enrollment
* Infection with human immunodeficiency virus (unless viral load is undetectable and CD4 count ≥ 200)
* Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen /[HbBsAg/] serology):
* Patients with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HBsAg) may be included if hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is undetectable at the time of screening. These patients must be willing to undergo monthly DNA testing and appropriate antiviral therapy as indicated by institutional standards
* Autoimmune disease requiring active therapy
* History of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
* Evidence of significant concurrent disease or medical condition that could interfere with the conduct of the study, or put the patient at significant risk including, but not limited to, significant cardiovascular disease (e.g., New York Heart Association class III or IV cardiac disease, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
* Ongoing systemic corticosteroid treatment, with the exception of corticosteroid use for other (non-tumor and non-immunosuppressive) indications up to a maximum of 10 mg/day of prednisone or equivalent
* Prior use of any monoclonal antibody within 4 weeks before the first mosunetuzumab administration
* Prior solid organ transplantation
* Pregnant or breast-feeding women, or intending to become pregnant during the study or within 3 months of the last dose of mosunetuzumab
A Phase 1 Study of SynKIR-310, Autologous T Cells Transduced with CD19 KIR-CAR, in Participants with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Теги: #Relapsed|Refractory
Локации: Colorado Blood Cancer Institute, part of Sarah Cannon Cancer Institute; Denver; Colorado; United States
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Описание
This first-in-human (FIH) trial is designed to assess the safety, feasibility and preliminary efficacy of a single intravenous (IV) dose of SynKIR-310 administered to participants with relapsed/refractory B-NHL.
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Критерии включения
* Adult 18 years of age and older.
* Histologically confirmed diagnosis of B-NHL before enrollment.
* Must have received prior CAR T or were unwilling/unable to receive prior CAR T.
* Must have refractory or relapsed disease after receiving 2 prior lines of therapies.
* If relapsed/refractory post-auto-SCT, then must have undergone auto-SCT at least 6 months prior to enrollment.
* If relapsed/refractory disease after allogeneic stem cell transplant (allo SCT) then must have undergone allo-SCT at least 6 months prior to enrollment and without evidence of graft versus host disease.
* Measurable disease at time of enrollment: At least one measurable lesion per Lugano Response Criteria (Cheson et al., 2014).
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
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Критерии исключения
* Previously treated with any investigational agent within 30 days prior to screening.
* Adequately treated non-melanoma skin cancer such as basal cell or squamous cell carcinoma
* Carcinoma-in-situ (e.g., cervix, bladder, breast) treated curatively and without evidence of recurrence for at least 3 years prior to enrollment.
* Any other malignancy which has been completely treated and remains in complete remission for ≥ 5 years prior to enrollment. Completely treated prostate cancer with prostate-specific antigen (PSA) level /< 1.0 may also be permitted.
* Known immunodeficiency disease.
* History or presence of active or clinically relevant primary central nervous system (CNS) disorder, such as seizure, encephalopathy, cerebrovascular ischemia/hemorrhage, cerebellar disease, or any autoimmune disease with CNS involvement. For primary CNS disorders that have recovered or are in remission, participants without recurrence within 2 years of planned study enrollment may be included.
* Uncontrolled hypertension, history of myocarditis or congestive heart failure, unstable angina, serious uncontrolled cardiac arrhythmia, or myocardial infarction within 6 months prior to study entry.
* Any active uncontrolled systemic fungal, bacterial or viral infection.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Oxygen Study-Orelabrutinib Combined With Obinutuzumab(O2) for First-Line Treatment of Marginal Zone Lymphoma
Oxygen Study-Orelabrutinib Combined With Obinutuzumab(O2) for First-Line Treatment of Marginal Zone Lymphoma: A Phase 2, Single-Arm, Prospective, Multicenter Clinical Study
Теги: #Newly diagnosed
Локации: The Affiliated Huaian No.1 People`s Hospital of Nanjing Medical University#Huai`an First People`s Hospital#; Huai`an,; Jiangsu; China
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Описание
This is a multi-center, prospective study. The main purpose is to evaluate the efficacy and safety of Orelabrutinib combined with Obinutuzumab for previously untreated MZL.
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Критерии включения
* Aged ≥18 years, gender not limited;
* Histopathologically confirmed CD20-positive marginal zone lymphoma including MALT, SMZL, NMZL;
* MZL that has progressed, recurred, or is not suitable for local treatment after previous local treatment (local treatments include surgery, radiotherapy, Helicobacter pylori treatment, and hepatitis C treatment);
* ECOG 0-2;
* Indication for treatment as judged by the investigator (symptomatic, with cytopenia, at risk of end-organ damage, bulky disease, persistent progression, or patient/&#39;s desire for treatment);
* Major organ function meets the following criteria: a) Complete blood count: Absolute neutrophil count ≥1.5×10/^9/L, platelets ≥75×10/^9/L, hemoglobin ≥75g/L; if accompanied by bone marrow invasion, absolute neutrophil count ≥1.0×10/^9/L, platelets ≥50×10/^9/L, hemoglobin ≥50g/L; b) Blood biochemistry: Total bilirubin ≤1.5 ULN, AST or ALT ≤2 ULN; serum creatinine ≤1.5 ULN; serum amylase ≤ULN; c) Coagulation function: International normalized ratio (INR) ≤1.5 ULN.
* Expected survival time ≥3 months;
* Voluntarily sign a written informed consent form before the trial screening.
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Критерии исключения
* Currently or previously diagnosed with other malignant tumors, unless curative treatment has been performed and there is evidence of no recurrence or metastasis within the last 5 years;
* Lymphoma involving the central nervous system or transformation to a higher grade;
* Active bleeding within 2 months prior to screening, or currently taking anticoagulant medications, or the investigator considers there to be a definite bleeding tendency;
* Major surgery within 6 weeks prior to screening or minor surgery within 2 weeks prior to screening;
* Active infection or uncontrolled HBV (positive for HBsAg and/or HBcAb and positive for HBV DNA titer), HCV Ab positive, HIV/AIDS, or other serious infectious diseases;
* Any mental or cognitive disorder that may limit the understanding, execution, and compliance with the informed consent form and the study;
* Pregnant or lactating women and women of childbearing age who are unwilling to take contraceptive measures;
* Need to continuously take drugs with moderate to severe inhibitory or strong inductive effects on cytochrome P450 CYP3A;
* Other conditions that the investigator considers unsuitable for participating in this trial.
Orelabrutinib Followed by Response-adapted Ultra-low Dose 4Gy Radiation as First-line Treatment of MALT Lymphoma
A Prospective, Multicenter, Phase II Study of Orelabrutinib Followed by Response-adapted Ultra-low Dose 4Gy Radiation as First-line Treatment of Local-stage Mucosa Associated Lymphoid Tissue Extranodal Marginal Zone Lymphoma
Теги: #Newly diagnosed
Локации: Fudan University Shanghai Cancer Center; Shanghai; Shanghai; China
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Описание
Investigate the efficacy and safety of Orelabrutinib followed by response-adapted ultra-low dose 4Gy radiation in the treatment of local-stage MALT lymphoma
* Having sufficient organ function: a) Hematopoietic function: Neutrophils ≥ 1.0 × 109/L, PLT ≥ 50 × 109/L, Hb ≥ 80g/L; b) Liver function: bilirubin ≤1.5 times the upper limit of normal (ULN), ALT and AST/<3 x ULN, serum albumin ≥ 30 g/L; c) Renal function: serum Cr/<1.5 × ULN, creatinine clearance rate ≥ 50mL/min (calculated according to the standard Cockcroft Gault formula, if renal dysfunction is caused by tumor compression, creatinine clearance rate ≥ 30mL/min); d) Coagulation function (unless the subject is receiving anticoagulant therapy and the coagulation parameters (PT/INR and APTT) are within the expected range of anticoagulant therapy at the time of screening): International standardized ratio (INR) ≤ 1.5 x ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 x ULN.
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Критерии исключения
* Recent major surgery (within 4 weeks prior to enrollment), except for diagnostic surgery
* Have uncontrolled intercurrent diseases (cardiovascular and cerebrovascular diseases, coagulation disorders, severe infectious diseases) including but not limited to: severe acute or chronic infection requiring systemic treatment, symptomatic congestive heart failure (NYHA III-IV) or symptomatic or poorly controlled arrhythmias, arterial hypertension (systolic blood pressure ≥ 160mmHg or diastolic blood pressure ≥100mmHg) that is not controlled even with standard treatment, unstable angina, active peptic ulcer or bleeding disorder;
* Severe concomitant diseases that interfere with treatment
* Active interstitial pneumonia
* Active chronic hepatitis B infection (defined as HBV DNA positive; patients with latent or prior hepatitis B infection (defined as positive for hepatitis B surface antigen or hepatitis B core total antibody) can be included if HBV-DNA is undetectable at screening. The above-mentioned patients must voluntarily undergo regular DNA tests and receive appropriate antiviral therapy as prescribed)
* Positive hepatitis C test result (for patients who are positive for HCV antibodies, only polymerase chain reaction (PCR) shows a negative HCV RNA can participate)
* Patients with active HIV and syphilis infections;
* Pregnant or lactating women
* Patients with multiple factors affecting oral medication (such as dysphagia, nausea, vomiting, chronic diarrhea, and intestinal obstruction)
* The researcher determined that patients are not suitable to participate in this study.
Linperlisib Combination With Obinutuzumab Frontline Treatment of Marginal Zone Lymphoma Patients (MZL)
A Single Arm, Open Center, Multicenter Clinical Study of Frontline Treatment of Marginal Zone Lymphoma Patients (MZL) With Linperlisib Combined With Obinutuzumab
Теги: #Newly diagnosed
Локации: The First Hospital of Jilin University; Changchun; Jilin; China
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Описание
This is a single arm, open label, national multicenter clinical study included patients with marginal zone lymphoma patients (MZL) , aim is to evaluate the efficacy and safety of first-line treatment with Linperlisib combined with obinutuzumab in patients with marginal zone lymphoma (MZL).
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Критерии включения
* 1. Age ≥ 18 years old, both male and female are acceptable; 2. Newly diagnosed marginal zone lymphoma confirmed by histopathology. Including extranodal MZL, intranodal MZL, and splenic MZL; 3. There is at least one measurable lesion: the longest diameter (LDi) of a lymph node lesion is greater than 1.5 cm or the LDi of an extra lymph node lesion is greater than 1 cm (according to the 2014 Lugano classification); 4. The physical status score of the Eastern Cooperative Oncology Group (ECOG) is ≤ 2; 5. Expected lifespan ≥ 12 weeks; 6. Have not received any previous anti-tumor treatment; 7. Possess sufficient bone marrow and organ functions; 8. All screening laboratory tests must be conducted according to the protocol requirements, and must be conducted within 7 days prior to enrollment. The values of laboratory tests conducted for screening must meet the following standards:
Blood routine examination (no blood transfusion within 14 days before screening, no use of granulocyte colony-stimulating factor (G-CSF), no medication correction):
1. Hemoglobin (Hb) ≥ 90 g/L;
2. Neutrophil count (ANC) ≥ 1.5 × 10/*9/L;
3. Platelets (PLT) ≥ 100 × 10/*9/L;
Biochemical examination:
1. TBIL/<1.5 x upper limit of normal range (ULN);
1. International Normalized Ratio (INR) ≤ 1.5 × ULN;
2. Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; 9. Women who have the possibility of pregnancy must undergo a serum pregnancy test within 7 days before the first use of the test drug, and the result must be negative. They must also be willing to use effective contraception methods during the trial period and within 1 year after the last administration of the test drug. For male participants whose partners are women of childbearing age, surgical sterilization should be performed, or they should agree to use efficient contraception methods during the trial period and one year after the last administration of the trial drug; 10. The subjects voluntarily joined this study, signed an informed consent form, had good compliance, and cooperated with follow-up
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Критерии исключения
* 1. Patients who have received any targeted PI3K therapy before enrollment; 2. History of other primary invasive malignant tumors that have not been relieved or have not been relieved for more than 3 years; 3. Patients with involvement of the central nervous system (meninges or brain parenchyma); 4. Individuals who are known to have allergies to any of the drugs in the study; 5. Participated in clinical trials of other drugs within 4 weeks prior to the start of the study; 6. Pregnant or lactating women; 7. Individuals with active infections, except for those with tumor related B symptoms and fever; 8. Combined diseases and medical history:
1. There are multiple factors that can affect oral medication, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
2. Individuals with a history of abuse of psychotropic drugs who are unable to quit or have mental disorders;
3. Subjects with any severe and/or uncontrolled illnesses, including:
1. Poor blood pressure control (systolic blood pressure ≥ 150mmHg or diastolic blood pressure ≥ 100 mmHg);
2. Suffering from ≥ grade 2 myocardial ischemia or myocardial infarction, arrhythmia /[including QTc ≥ 450ms (male), QTc ≥ 470ms (female)/], and ≥ grade 2 congestive heart failure /[New York Heart Association (NYHA) classification/];
3. Active interstitial pneumonia or other chronic lung diseases leading to severe impairment of lung function, defined as FEV1 and DLCOc/<60% of normal predicted values; History of interstitial pneumonia caused by COVID-19.
4. Liver abnormalities:
5. Decompensated cirrhosis (Child Pugh liver function rating B or C)
6. Known history of liver disease with clinical significance. Including viral hepatitis, known carriers of hepatitis B virus (HBV) must exclude active HBV infection, i.e. HBV DNA positive (/>2500 copies/mL or />500IU/mL, and greater than the upper limit of normal); Known to be infected with hepatitis C virus (HCV) and HCV RNA positive (/>1 × 103 copies/mL). Note: hepatitis B HBsAg positive subjects who meet the inclusion conditions, whether their HBV DNA is measurable or not, need to continue antiviral treatment (nucleoside analogues are recommended) and regularly monitor HBV DNA; For subjects with positive HBcAb but negative HBsAg in hepatitis B, HBV DNA should be monitored regularly and preventive antiviral treatment should be recommended; HCV RNA should be regularly monitored in subjects with hepatitis C.
7. Patients with renal failure requiring hemodialysis or peritoneal dialysis;
8. Subjects with uncontrolled pleural effusion, pericardial effusion, or ascites that require repeated drainage;
9. Poor control of diabetes (FBG/>10mmol/L);
10. Urine routine shows urinary protein ≥++and confirms 24-hour urinary protein quantification/>1.0g; 9. History of immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; 10.According to the researchers assessment, there are accompanying diseases that pose a serious threat to patient safety or affect the completion of the study.