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Active Not RecruitingNCT03984448

Testing the Addition of a New Anti-cancer Drug, Venetoclax, to Usual Chemotherapy for High Grade B-cell Lymphomas

Randomized Phase II/III Study of Venetoclax (ABT199) Plus Chemoimmunotherapy for MYC/BCL2 Double-Hit and Double Expressing Lymphomas

Status
Active Not Recruiting
Phase
Phase 2 / Phase 3
Study type
Interventional
Enrollment
363 (estimated)
Sponsor
National Cancer Institute (NCI) · NIH
Sex
All
Age
18 Years – 80 Years
Healthy volunteers
Not accepted

Summary

This phase II/III trial tests whether it is possible to decrease the chance of high-grade B-cell lymphomas returning or getting worse by adding a new drug, venetoclax to the usual combination of drugs used for treatment. Venetoclax may stop the growth of cancer cells by blocking a protein called Bcl-2. Drugs used in usual chemotherapy, such as rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax together with usual chemotherapy may work better than usual chemotherapy alone in treating patients with high-grade B-cell lymphomas, and may increase the chance of cancer going into remission and not returning.

Detailed description

PRIMARY OBJECTIVE: I. To compare the progression-free survival (PFS) of rituximab (R)-chemotherapy plus venetoclax versus R-chemotherapy alone in MYC/BCL2 double-hit and double expressing lymphomas. SECONDARY OBJECTIVES: I. To compare the overall survival (OS) of R-chemotherapy plus venetoclax versus R-chemotherapy alone in MYC/BCL2 double-hit and double expressing lymphomas. II. To compare the event-free survival (EFS) of R-chemotherapy plus venetoclax versus R-chemotherapy alone in MYC/BCL2 double-hit and double expressing lymphomas. III. To assess the toxicity profile of the experimental regimens in MYC/BCL2 double-hit and double expressing lymphomas using Common Terminology Criteria for Adverse Events (CTCAE) and patient reported outcomes (PRO)-CTCAE. IV. To compare response rates of R-chemotherapy plus venetoclax versus R-chemotherapy alone in MYC/BCL2 double-hit and double expressing lymphomas. V. To estimate differences in response rates, EFS, PFS, and OS of R-chemotherapy plus venetoclax versus R-chemotherapy alone within each of the disease subtypes (double hit lymphoma \[DHL\] and double expressing lymphoma \[DEL\]). VI. To determine whether cell of origin and intensity of the MYC and BCL2 protein expression on diagnostic tumor biopsy correlate with PFS, EFS, and OS. VII. To determine whether local subtyping results for DHL and DEL are consistent with central analysis (phase II only). OUTLINE: Patients are randomized to Arm 1 or Arm 2. ARM 1 (DEL): Patients with DEL receive R-CHOP chemotherapy regimen consisting of rituximab intravenously (IV) on day 1, cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone orally (PO) once daily (QD) on days 1-5. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo position emission tomography (PET) scan, computed tomography (CT) scan and blood sample collection and may undergo bone marrow biopsy and lumbar puncture throughout the study. ARM 1 (DHL): Patients with DHL receive dose-adjusted (DA)-EPOCH-R chemotherapy regimen consisting of rituximab IV on day 1, doxorubicin hydrochloride IV on days 1-4, etoposide IV on days 1-4, vincristine sulfate IV on days 1-4, prednisone PO twice daily (BID) on days 1-5, and cyclophosphamide IV on day 5. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET scan, CT scan and blood sample collection and may undergo bone marrow biopsy and lumbar puncture throughout the study. ARM 2 (DEL): Patients with DEL receive R-CHOP chemotherapy regimen as in Arm 1. Patients also receive venetoclax PO QD on days 4-8 of cycle 1 and days 1-5 for cycles 2-6. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET scan, CT scan and blood sample collection and may undergo bone marrow biopsy and lumbar puncture throughout the study. ARM 2 (DHL): Patients with DHL receive DA-EPOCH-R chemotherapy regimen as in Arm 1. Patients also receive venetoclax PO QD on days 4-8 of cycle 1 and days 1-5 for cycles 2-6. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET scan, CT scan and blood sample collection and may undergo bone marrow biopsy and lumbar puncture throughout the study. After completion of study treatment, patients are followed up every 12 weeks for 2 years, then every 24 weeks for up to 5 years, and then every 6 months for up to 10 years from registration.

Conditions

Interventions

TypeNameDescription
PROCEDUREBiospecimen CollectionUndergo blood sample collection
PROCEDUREBone Marrow BiopsyUndergo bone marrow biopsy
PROCEDUREComputed TomographyUndergo CT scan
DRUGCyclophosphamideGiven IV
DRUGDoxorubicin HydrochlorideGiven IV
DRUGEtoposideGiven IV
PROCEDURELumbar PunctureUndergo lumbar puncture
PROCEDUREPositron Emission TomographyUndergo PET scan
DRUGPrednisoneGiven PO
BIOLOGICALRituximabGiven IV
DRUGVenetoclaxGiven PO
DRUGVincristine SulfateGiven IV

Timeline

Start date
2019-10-22
Primary completion
2028-04-01
Completion
2028-04-01
First posted
2019-06-13
Last updated
2026-04-13

Locations

636 sites across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT03984448. Inclusion in this directory is not an endorsement.