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

Conditions

• Diffuse Large B-Cell Lymphoma
• Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
• Double-Expressor Lymphoma
• EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
• High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
• High Grade B-Cell Lymphoma, Not Otherwise Specified
• Neoplastic Cells With Double Expression of MYC and BCL2 Proteins Present
• Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma

Eligibility Criteria

Sex

ALL

Age

18 Years - 80 Years

Healthy Volunteers

Not accepted

Interventions

• Biospecimen Collection — PROCEDURE
  Undergo blood sample collection
• Bone Marrow Biopsy — PROCEDURE
  Undergo bone marrow biopsy
• Computed Tomography — PROCEDURE
  Undergo CT scan
• Cyclophosphamide — DRUG
  Given IV
• Doxorubicin Hydrochloride — DRUG
  Given IV
• Etoposide — DRUG
  Given IV
• Lumbar Puncture — PROCEDURE
  Undergo lumbar puncture
• Positron Emission Tomography — PROCEDURE
  Undergo PET scan
• Prednisone — DRUG
  Given PO
• Rituximab — BIOLOGICAL
  Given IV
• Venetoclax — DRUG
  Given PO
• Vincristine Sulfate — DRUG
  Given IV

Study Details

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.

Key Dates

Start date

Oct 22, 2019

Status verified

Jan 2026

Primary completion

Apr 1, 2028

Completion

Apr 1, 2028

Study Design

Enrollment

363 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Arm 1 (R-CHOP, DA-EPOCH-R)
  DEL: Patients with DEL receive R-CHOP chemotherapy regimen consisting of rituximab IV on day 1, cyclophosphamide IV on day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and prednisone PO QD on days 1-5. 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. DHL: Patients with DHL receive 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 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
• Experimental: Arm 2 (R-CHOP, DA-EPOCH-R, venetoclax)
  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. 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.

Primary Outcome Measure

Progression-free survival (PFS) (phase II) [ Time Frame: From randomization date until the earlier of disease progression, or death from any cause, assessed up to 10 years ]

Locations (636)

Find similar trials in Birmingham, AL

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