Randomized Phase II/III Study of Venetoclax (ABT 199) Plus Chemoimmunotherapy for MYC/BCL2 Double-Hit and Double-Expressing Lymphomas.

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 Eligibility:
• Pathologic diagnosis of diffuse large B-cell lymphoma (DLBCL) or high grade B-cell lymphoma (HGBCL).
• High grade B-cell lymphoma with translocations of MYC and BCL2 (double hit lymphoma, DHL), or DLBCL or high grade B-cell lymphoma not otherwise specified (NOS) with protein expression by immunohistochemistry (IHC) of both MYC (greater than or equal to 40 percent) and BCL2 (greater than or equal to 50 percent) in the absence of dual translocations (double expressing lymphoma, DEL). Local determination of fluorescence in situ hybridization (FISH) and IHC will be performed per standardized guidelines and will be acceptable for study entry.
• No prior treatment for DLBCL/HGBCL is allowed with the exception of corticosteroids administered for palliation, or a single cycle of either rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or dose adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) administered prior to enrollment.
• No active ischemic heart disease or congestive heart failure, and left ventricular ejection fraction (LVEF) greater than or equal to 45 percent.
• No active hepatitis B or hepatitis C infection.
Phase II/III
Alison Conlin, M.D.
Laurie Miller

The Pacific Cancer Research Consortium clinical trials are offered at multiple locations throughout Oregon, Washington, Alaska, California, and Idaho. To find a location near you, please contact the Patient Engagement Center at 844-552-2734.