OncoTrials - мониторинг клинических исследований

Описание

The study will evaluate the progression-free survival benefit of duvelisib monotherapy as compared to investigator`s choice of gemcitabine or bendamustine in participants with relapsed/refractory nodal T cell lymphoma with TFH phenotype.

Критерии включения

• * Pathologically confirmed nodal T cell lymphoma with TFH phenotype according to the criteria of the World Health Organization classification (Swerdlow 2017, Alaggio 2022) including any one of Angioimmunoblastic T cell lymphoma (AITL), follicular T cell lymphoma, and other nodal peripheral T cell lymphoma (PTCL) with a TFH phenotype.
• * Relapsed or refractory to at least 1 prior systemic, cytotoxic therapy for T cell lymphoma.
• * Measurable disease as defined by Lugano 2014 criteria (Cheson 2014) for T cell lymphoma.

Критерии исключения

• * Cutaneous-only disease.
• * Received prior allogeneic transplant any time in the past or received autologous transplant within 60 days prior to the first dose of study drug.
• * Received prior treatment with a phosphoinositide-3-kinase (PI3K) inhibitor.
• * Prior exposure to planned study treatment investigator`s choice therapy (gemcitabine or bendamustine) within 60 days prior to the first dose of study drug.
• Other protocol-defined criteria apply.

Описание

This research is being done to evaluate tazemetostat in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy as a possible treatment for peripheral T-Cell Lymphoma (PTCL).

The name of the study drugs involved in this study are:

* Tazemetostat (a type of inhibitor for Enhancer of Zeste Homolog 2 (EZH2))
* Standard of care CHOP therapy:

* Cyclophosphamide (a type of alkylating agent)
* Doxorubicin (a type of anthracycline antibiotic)
* Vincristine (a type of vinca alkaloid)
* Prednisone (a type of corticosteroid)
* Standard of care BEAM conditioning regimen for autologous stem cell transplant:

* Carmustine (a type of alkylating agent)
* Etoposide (a type of Topoisomerase II inhibitor)
* Cytarabine (a type of antineoplastic)
* Melphalan (a type of alkylating agent)

Критерии включения

• * Participants must have histologically or cytologically confirmed peripheral T cell lymphoma of one of the following subtypes: PTCL-NOS, Follicular helper T-cell lymphoma (ICC 2022) or Nodal T-follicular helper (TFH) cell lymphoma by (WHO 2022) which includes follicular helper T-cell lymphoma, AITL and follicular helper T cell lymphoma, follicular type, EATL, MEITL. All pathology will be reviewed at BWH. BWH review is not required prior to enrollment and patients may be enrolled based upon local pathology analysis. Ten blank slides will be required from outside tumor biopsy for correlative studies.
• * No prior treatment for T NHL with the exception of one cycle of CHOP or CHOEP or 7 days of corticosteroids at a dose of up to prednisone 60 mg or equivalent for palliation of disease related symptoms so long as the corticosteroids are discontinued prior to tazemetostat prephase or cycle 1 of treatment if not receiving the prephase.
• * At least one bi-dimensionally measurable lesion, defined as />1.5 cm in its longest dimension as measured by CT.
• * Age ≥18 years.
• * ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
• * Participants must have adequate organ and marrow function as defined below:
• * absolute neutrophil count ≥1,000/mcL (750 mcl if bone marrow involvement with lymphoma)
• * platelets ≥75,000/mcL (25,000 if bone marrow involvement with lymphoma)
• * total bilirubin ≤ institutional upper limit of normal (ULN)
• * AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
• * creatinine ≤ 1.5 x institutional ULN OR
• * glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2
• * Because the effects of tazemetostat on human immunodeficiency virus (HIV)-infected participants and anti-retroviral therapy is unknown, patients with known HIV infection are not eligible for this trial.
• * For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• * Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment, are not eligible.
• * Left ventricular ejection fraction of /> 50% as assessed by echocardiography or multi-gate acquisition (MUGA) scan.
• * The effects of tazemetostat on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. For women of childbearing potential, a negative serum pregnancy test result within 7 days prior to commencement of dosing. Women who are considered not to be of childbearing potential are not required to have a pregnancy test.
• * Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of tazemetostat administration.Women should use effective contraceptive methods beginning ≥28 days prior to initiating, during tazemetostat treatment, and for at least 6 months after the final dose of tazemetostat
• * Ability to understand and the willingness to sign a written informed consent document.

Критерии исключения

• * Participants who have had chemotherapy for T cell lymphoma prior to entering the study (except 1 cycle of CHOP/CHOEP as noted above). Prior radiotherapy may be allowed after discussion with the sponsor-investigator so long as the area radiated was not the only measurable site of disease.
• * Participants who are receiving any other investigational agents.
• * Patients with known central nervous system involvement with lymphoma
• * History of allergic reactions attributed to compounds of similar chemical or biologic composition to tazemetostat or other agents used in study.
• * Prior organ transplantation.
• * Current motor or peripheral neuropathy with grade />1.
• * History of other malignancy that could affect compliance with the protocol or interpretation of results. Exceptions include:
• * Patients with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix at any time prior to the study are eligible.
• * Patients with any malignancy appropriately treated with curative intent and the malignancy has been in remission without treatment for /> 2 years prior to enrollment are eligible.
• * Patients with low-grade, early-stage prostate cancer (Gleason score 6, Stage 1 or 2) with no requirement for therapy at any time prior to study are eligible.
• * Uncontrolled intercurrent illness.
• * Pregnant women and women intending to become pregnant are excluded from this study because chemotherapeutic agents used in this study have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with tazemetostat, breastfeeding should be discontinued if the mother is treated with tazemetostat.
• * Evidence of significant, uncontrolled, concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina)
• * Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis
• * Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or significant infections within 2 weeks before the start of Cycle 1.
• * Inability to swallow pills.
• * Because no dosing or adverse event data are currently available on the use of tazemetostat in combination with CHOP in participants /<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.

Описание

This study is a multi-center, global, open-label, Phase 1b/2 clinical study, and it will be conducted at multiple study sites in several countries, including Japan, Korea, and Singapore, to reveal the safety, tolerability, dose limiting toxicity (DLT), maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D), pharmacokinetics (PK), and preliminary efficacy of BCV in patients with relapsed or refractory lymphoma and to assess the efficacy and safety of Brincidofovir (SyB V-1901, BCV) in patients with relapsed or refractory Extranodal Natural Killer/T-cell Lymphoma (ENKL).

This study consists of 2 parts and will enroll a total (maximum) of 43 male and female participants who meet the eligibility criteria (Phase 1b part: Up to 18 participants /[3 to 6 participants in each of the 3 cohorts/], Phase 2 part: 25 participants).

Критерии включения

• * Patients who are histopathologically diagnosed with ENKL based on the World Health Organization (WHO) Classification of Malignant Lymphoma 5th Edition (WHO-HAEM5) (can be enrolled in the Phase 1b part and the Phase 2 part) or patients diagnosed with EBV-positive nodal T- and NK-cell lymphoma (EBV + nTNKCL), nodal T-follicular helper cell lymphoma (nTFHcL) (including angioimmunoblastic T-cell lymphoma (AITL) as defined in the WHO Classification, 4th Edition), peripheral T-cell lymphoma not otherwise specified (PTCL, NOS), anaplastic large cell lymphoma (ALCL), diffuse large B-cell lymphoma (DLBCL) (e.g., DLBCL, NOS), or adult T-Cell Leukemia Lymphoma (ATLL) (can only be enrolled in the Phase 1b part)
• * Patients with relapsed or refractory lymphoma and previously treated with systemic chemotherapy (history of multidrug chemotherapy including L-asparaginase such as SMILE therapy for ENKL is mandatory) who are ineligible for other systemic therapies
• * Patients with the following Eastern Cooperative Oncology Group (ECOG) Performance Status (PS):
• * Phase 1b part: 0-1
• * Phase 2 part: 0-2

Критерии исключения

• * Patients with another active malignant tumor requiring treatment
• * Patients with NCI-CTCAE Grade 2 or higher diarrhea (increase of 4 or more bowel movements per day compared to usual number of bowel movements) within 7 days prior to starting the first dose of BCV
• * Graft-Versus-Host Disease (GVHD) patients requiring immunosuppressive agents
• * Patients with a history of Cidofovir intolerance
• * Patients with a history of being diagnosed with cirrhosis

Описание

The researchers are doing this study to find out whether enasidenib is a safe treatment for people with angioimmunoblastic T-cell lymphoma (AITL) that has an IDH2 mutation. The researchers will look at the safety of enasidenib when it is given alone or in combination with the drug rituximab.

Критерии включения

• * Pathologically-confirmed AITL at the enrolling institution, with confirmed IDH2 mutation (by MSK ddPCR). For R/R patients, disease must have relapsed or progressed after at least one systemic therapy, diagnostic tumor samples have at least 5% tumor. i) IDH2 hotspot mutation confirmed by CAP/CLIA-certified NGS testing panel. Only cases with confirmed mutations detected />1% VAF will be eligible.
• * Age ≥18 years at time of enrollment Previous systemic anti-cancer therapy for AITL must have been discontinued at least 2 weeks or 5 half-lives (whichever is longer) prior to treatment.
• i) ii) See section 6.2 Subject Exclusion Criteria for guidelines regarding adjuvant and maintenance therapy for prior malignancy. Patients who have received localized RT as part of their immediate prior therapy may be allowed to enroll with shorter washout period after discussion with the MSKCC Principal Investigator ii) Patients who have received localized RT as part of their immediate prior therapy may be allowed to enroll with shorter washout period after discussion with the MSKCC Principal Investigator iii) Systemic corticosteroids must be tapered to 25 mg/day prednisone (or equivalent) upon start of investigational treatment iv) 4) 5) 6) 7) 8) 9) Topical steroids for treating cutaneous involvement of AITL is permitted Performance status, as assessed in the ECOG grading system, ≤2 Laboratory criteria (use of GCSF and/or blood product transfusions to reach eligibility criteria must be discussed with the MSK PI on a case-by-case basis)

Критерии исключения

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