OncoTrials - мониторинг клинических исследований

Описание

This is a phase II study in patients with previously treated immunoglobulin light-chain (AL) Amyloidosis to evaluate the efficacy and safety of teclistamab

Критерии включения

• * Biopsy confirmed AL amyloidosis
• * Patients must have received at least one line of treatment, including daratumumab and bortezomib
• * Relapse from previous treatment, or less than partial response after two cycles of treatment/less than very good partial response after three cycles of treatment
• * dFLC /> 50mg/L

Критерии исключения

• * Previous anti-BCMA targeted therapy
• * Co-morbidity of uncontrolled infection
• * Co-morbidity of other active malignancy
• * Co-diagnosis of multiple myeloma or waldenstrom macroglobulinemia
• * Co-morbidity of grade 2 Mobitz II or grade 3 atrioventricular block (expect for those with implanted pacemaker)
• * Co-morbidity of sustained or recurrent nonsustained ventricular tachycardia
• * Seropositive for human immunodeficiency virus
• * Hepatitis B virus (HBV)-DNA /> 1000 copies/mL
• * Seropositive for hepatitis C (except in the setting of a sustained virologic response)
• * Neutrophil /<1×10E9/L, hemoglobin /< 8g/dL, or platelet /< 75×10E9/L.
• * Severely compromised hepatic or renal function: alanine transaminase (ALT) or aspertate aminotransferase (AST) /> 5 × upper limit of normal (ULN), total bilirubin /> 2 × ULN, eGFR /< 20 mL/min, or receiving renal replacement therapy

Описание

This study is a multicenter, open label, fixed dose exploratory clinical trial with an expected enrollment of 30 subjects. The main objective is to evaluate the safety of targeted BCMA autologous CART cell injection in the treatment of recurrent or refractory light chain amyloidosis in subjects, preliminarily verify the effectiveness of targeted BCMA autologous CART cell injection in the treatment of recurrent or refractory light chain amyloidosis in subjects, and explore the pharmacokinetic, pharmacodynamic, and immunogenic characteristics of targeted BCMA autologous CART cell injection after reinfusion.

Критерии включения

• - Participants must meet all inclusion criteria, and only those who do not meet any exclusion criteria can be enrolled
• 1. Participants must personally sign the informed consent form approved by the ethics committee in writing before the start of the study;
• 2. The age of the subject is ≥ 18 years old;
• 3. Diagnosed with light chain amyloidosis through pathological examination;
• 4. Subjects with recurrent/refractory light chain amyloidosis who have previously received second-line or higher treatment;
• 5. dFLC /> 50mg/L
• 6. Expected survival period ≥ 12 weeks;
• 7. ECOG score ≤ 2 points;
• 8. Female subjects with fertility should agree to take effective contraceptive measures from the date of signing the informed consent form until 365 days after reinfusion. Effective contraceptive measures are defined as abstinence or using contraceptive methods with an annual failure rate of less than 1% as specified in the plan;
• 9. Prior to enrollment, participants must have appropriate organ function and meet all of the following test results:
• 9.1 Absolute neutrophil count ≥ 1.0 × 109/L /[allowed to use granulocyte colony-stimulating factor (G-CSF) support/]; 9.2 Platelet count ≥ 50 × 109/L; 9.3 Hemoglobin ≥ 8 g/dl; 9.4 Bilirubin value ≤ 1.5 x upper limit of normal (ULN); 9.5 ALT or AST ≤ 2.5 times the upper limit of normal (ULN) (with liver involvement ≤ 5 times the upper limit of normal); 9.6 Mayo 2004 Stage I-IIIa participants; 9.7 Stable coagulation function: INR ≤ 1.5, APTT ≤ 1.2 x upper limit of normal (ULN); Basic blood oxygen saturation is greater than 92% in indoor natural air environment.

Критерии исключения

• -
• Subjects who meet any of the following criteria will be excluded:
• 1. Subjects who have received the following previous treatments:
• 1.1 Individuals who have received gene therapy prior to enrollment; 1.2 Subjects who received live vaccines within 4 weeks prior to enrollment; 1.3 Received other intervention clinical drug treatments within 12 weeks prior to single collection;
• 2. Patients with central involvement or complete intestinal obstruction;
• 3. Patients with moderate to severe pleural and peritoneal effusion who are difficult to control with conventional treatment and require continuous catheterization and drainage;
• 4. Active malignant tumors within the past 5 years, unless they are curable tumors that have been significantly cured, such as basal or squamous cell carcinoma, cervical or breast carcinoma in situ, etc;
• 5. Subjects with positive hepatitis B B surface antigen (HBsAg) and abnormal detection of HBV DNA in peripheral blood (abnormal detection of HBV DNA is defined as: quantitative detection of HBV DNA is higher than the detection limit of the testing center or higher than the normal reference value range of the testing center or positive qualitative detection of HBV DNA); Individuals with positive hepatitis C virus (HCV) antibodies and positive hepatitis C virus (HCV) RNA in peripheral blood; Individuals who are HIV antibody positive; Individuals who test positive for Cytomegalovirus (CMV) DNA; Positive RPR results in syphilis testing;
• 6. There are uncontrollable active infections (excluding CTCAE grade 2 urinary and reproductive system infections and upper respiratory tract infections);
• 7. Severe heart disease: including but not limited to unstable angina, myocardial infarction (within 6 months before screening), congestive heart failure (NYHA classification ≥ III), 24-hour dynamic electrocardiogram showing ventricular arrhythmia and atrioventricular block, positive six minute walk test, interventricular septum and left ventricular posterior wall thickness/>1.5cm;
• 8. Hypertensive subjects who cannot be controlled by drug treatment;
• 9. Previous treatment toxicity reactions have not improved to baseline or ≤ grade 1 (NCI-CTCAE v5.0 version, except for hair loss and clinically insignificant laboratory test abnormalities);
• 10. Have undergone major surgery within 2 weeks prior to enrollment, or plan to undergo surgery during the waiting period for reinfusion or within 12 weeks after receiving study treatment (excluding planned local anesthesia surgery);
• 11. Solid organ transplant recipients;
• 12. Pregnant or lactating women;
• 13. Subjects with previous central nervous system disorders (such as cerebral aneurysms, epilepsy, stroke, senile dementia, mental illness, etc.) or consciousness disorders;
• 14. Other researchers have identified unstable systemic diseases, including but not limited to severe liver, kidney, or metabolic diseases that require drug treatment;
• 15. Known to have life-threatening allergic reactions, hypersensitivity reactions, or intolerance to cellular preparations or their components;
• 16. Patients diagnosed by researchers as having bleeding, severe thrombosis, or genetic/acquired bleeding and severe thrombosis (including hemophilia, coagulation dysfunction, thrombocytopenia, splenomegaly, etc.), or patients undergoing thrombolytic or anticoagulant therapy; Researchers believe that there are other situations that are not suitable for inclusion.

Описание

A Phase II study of HBI0101 (NXC-201) BCMA-CART in Multiple Myeloma and Light-chain Amyloidosis Patients. The goal of the study is to evaluate the efficacy and safety of HBI0101 CART.

Критерии включения

• 1. ≥18 years of age at the time of signing informed consent.
• 2. Voluntarily signed informed consent form.
• 3. Diagnosis of multiple myeloma and/or light-chain amyloidosis with relapsed or refractory disease, with measurable disease at screening visit
• 4. Subject suffering from multiple myeloma must have been exposed to at least two prior lines of therapy including proteasome inhibitor, immunomodulatory (IMiDs) therapy or anti-CD38 antibody, or functionally high-risk patients (i.e. first relapse within 18 months of treatment initiation) may be included.
• Subject with amyloidosis must have been exposed to at least one prior line of therapy which includes proteasome inhibitor or anti-CD38 antibody, or subjects with insufficient response (i.e. not achieving a VGPR or CR after exposure to at least an anti-CD38 antibody and a proteasome inhibitor) may be included.
• 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
• 6. Women of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone a hysterectomy or tubal ligation or who has not been naturally postmenopausal for at least 24 consecutive months, must have a negative serum pregnancy test prior to treatment. All sexually active WCBP and all sexually active male subjects must agree to use effective methods of birth control throughout the study.
• 7. Recovery to ≤ Grade 2 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 3 neuropathy.
• 8. Ability and willingness to adhere to the study visit schedule and all protocol requirements.
• 9. Subjects with relapsed multiple myeloma who have previously undergone allogenic stem cell transplantation must have no evidence of graft versus host disease after cessation of any immunosuppressive therapy for at least one month before recruitment to the study.

Критерии исключения

• 1. Contraindication to a study treatment/procedure or is anticipated to receive treatment/procedure that may preclude performance of study procedures.
• 2. Known bulky central nervous system disease.
• 3. Inadequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) /> 2.5 x upper limit of normal (ULN) and direct bilirubin /> 4x ULN.
• 4. Inadequate renal function defined by serum creatinine clearance/estimated clearance of /<20(ml/min).
• 5. International ratio (INR) or partial thromboplastin time (PTT) /> 2 x ULN, unless on a stable dose of anticoagulant for a thromboembolic event (provided this event is not an exclusion criteria).
• 6. Inadequate bone marrow function defined by absolute neutrophil count (ANC) /< 1000 cells/mm/^3, platelet count /< 30,000 mm/^3, or hemoglobin /< 8 g/dL. Subjects with absolute lymphocyte count /< 300 cells/mm/^3 may be excluded (due to potential challenges with producing CART cells), per investigator judgement.
• 7. Echocardiogram with left ventricular ejection fraction /< 40%.
• 8. Ongoing treatment with chronic immunosuppressant such as cyclosporine or systemic steroids (physiological replacement doses of steroids are allowed up to 12 mg/m/^2/d hydrocortisone or equivalent)
• 9. Significant co-morbid condition or disease which in the judgment of the Investigator would place the subject at undue risk or interfere with the study; examples include, but are not limited to, cirrhotic liver disease, sepsis, recent significant traumatic injury, and other conditions.
• 10. Known human immunodeficiency virus (HIV) positive status.
• 11. Active Hepatitis B or Hepatitis C active infection.
• 12. Active CMV infection.
• 13. Known history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within 3 months.
• 14. Chronic atrial fibrillation with uncontrolled heart rate.
• 15. Second primary malignancies that has required therapy in the last 2 years or is not in complete remission.
• 16. Subjects who have had a venous thromboembolic event (e.g., pulmonary embolism or deep vein thrombosis) requiring anticoagulation and who meet any of the following criteria:
• 1. Have been on a stable dose of anticoagulation for /< 1 month (except for acute line insertion induced thrombosis.)
• 2. Have had a Grade 2, 3, or 4 hemorrhage in the last 30 days
• 3. Are experiencing continued symptoms from their venous thromboembolic event (e.g. continued dyspnea or oxygen requirement).
• 17. Pregnant or lactating women.
• 18. Participation in another interventional clinical trial within 30 days prior to screening visit.

Описание

The goal of this observational study is to study the effectiveness and complications of novel immunotherapies used in the treatment of multiple myeloma in routine care in Norway. The aim is to close knowledge gaps, generate evidence for future clinical trials and contribute to future consensus on how to monitor for adverse events, and what mitigation strategies should be implemented, so that we can increase patient survival and quality-of-life.

Критерии включения

• * Participants age ≥ 18 years
• * Prior diagnosis of one of the following
• * Multiple myeloma as defined according to IMWG criteria
• * Primary plasma cell leukemia as defined according to IMWG consensus definition
• * AL-amyloidosis as defined according to IMWG criteria
• * Planned treatment with one of the following outside clinical trials (list to be amended based on approvals within the EU):
• * Teclistamab (Tecvayli)
• * Elranatamab (Elrexfio)
• * Talquetamab (Talvey)
• * Idecabtagene vicleucel (ide-cel/Abecma)
• * Ciltacabtagene autoleucel (cilta-cel/Carvykti)

Критерии исключения

• * None

Описание

This study aims to evaluate the use of teclistamab in systemic AL amyloidosis and answer whether teclistamab can improve the rate of complete hematological response.

This is a single-arm, multi-center, prospective study. Participants will receive the single drug teclistamab, which the investigator deems the best choice.

Критерии включения

• 1. Diagnosis of systemic AL amyloidosis;
• 2. Patients must have received standard-of-care daratumumab, bortezomib, they do not have at least one organ response, and have not get complete hematological response;
• 3. Life expectancy greater than 12 weeks;
• 4. HGB ≥70g/L;
• 5. Blood oxygen saturation /> 90%;
• 6. Total bilirubin (TBil) ≤3×upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0×ULN;
• 7. Informed consent explained to, understood by and signed by the patient.

Критерии исключения

• 1. Fulfill with the criteria of active multiple myeloma or active lymphoplasmacytic lymphoma.
• 2. Presence of other tumors which is/are in advanced malignant stage and has/have systemic metastasis;
• 3. Severe or persistent infection that cannot be effectively controlled;
• 4. Presence of severe autoimmune diseases or immunodeficiency disease;
• 5. Patients with active hepatitis B or hepatitis C (/[HBVDNA+/] or /[HCVRNA+/]);
• 6. Patients with HIV infection or syphilis infection;
• 7. Any situations that the researchers believe will increase the risks for the subject or affect the results of the study.