Last updated on December 2019

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


Brief description of study

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 Study Description

PRIMARY OBJECTIVES:

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. (Key Secondary Objective) 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 correlate with PFS, EFS, and OS.

VII. To determine whether local subtyping results for DHL and DEL are consistent with central analysis.

OUTLINE: Patients are randomized to Arm A or Arm B.

ARM A (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.

ARM A (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.

ARM B (DEL): Patients with DEL receive R-CHOP chemotherapy regimen as in Arm A. 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.

ARM B (DHL): Patients with DHL receive DA-EPOCH-R chemotherapy regimen as in Arm A. 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.

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.

Clinical Study Identifier: NCT03984448

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