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

Running, not enrolling · Phase 2/Phase 3

Conditions studied: 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

In brief

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 facts

Study ID

NCT03984448

Run by

National Cancer Institute (NCI)

People needed

363

Starts

2019-10-22

Expected to finish

2028-04-01

Last updated by the study team

2026-08-04

Who can join

Age: 18 and older, up to 80. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Pathologic diagnosis of diffuse large B-cell lymphoma (DLBCL) or high grade B-cell lymphoma not otherwise specified (HGBCL not otherwise specified [NOS]). Eligible subtypes include DLBCL NOS, Epstein Barr Virus positive (EBV+) DLBCL, HGBCL NOS and DLBCL/HGBCL transformed from an underlying indolent B-cell lymphoma. Patients with T-cell/histiocyte rich large B-cell lymphoma and primary mediastinal B-cell lymphoma are not eligible
• Double hit lymphoma (DHL) or double expressing lymphoma (DEL)
• DHL is defined as high grade B-cell lymphoma with one of the below:
• Translocations of MYC and BCL2
• Translocations of MYC and BCL2 and BCL6 (triple hit lymphoma)
• Translocations of MYC and BCL6 without BCL2 translocation BUT with immunohistochemistry (IHC) expression of BCL2 (>=50%)
• DEL is defined as DLBCL or high grade B-cell lymphoma not otherwise specified (NOS) with protein expression by IHC of both MYC (>= 40%) and BCL2 (>= 50%) in the absence of dual translocations of both MYC and BCL2 and/or BCL6). (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, but local IHC and FISH results for MYC must be submitted for central review in order to determine eligibility if enrolling as DEL based on local results during phase II. Central pathology review is no longer required as of Update #03.
• The diagnosis of DLBCL/HGBCL and assessment of DEL/DHL will be performed per standardized guidelines at local institutions and patients will be enrolled based on local determination. Cases submitted as DHL must demonstrate the presence of a MYC translocation as well as a translocation of BCL2, BCL6, or both. Cases submitted as a DEL must demonstrate appropriate IHC protein expression of MYC and BCL2, and be negative for translocations of MYC along with translocations of BCL2 and/or BCL6 by FISH. Patients with MYC translocations and no translocations of either BCL2 or BCL6 are eligible for the DEL cohort
• Patients must have FDG-avid disease on PET/CT
• 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. Corticosteroids or local radiation therapy are also allowed. Patients may have received intrathecal chemotherapy for CNS prophylaxis prior to registration. This single pre-registration cycle is being allowed to facilitate enrolling patients who required immediate initiation of therapy for rapidly progressing disease, or for patients where FISH or IHC results returned after initiation of chemotherapy rendered them protocol eligible. Patients with DLBCL or HGBCL transformed from an underlying indolent lymphoma cannot have received prior chemotherapy, but prior anti-CD20 monoclonal antibody therapy or radiation therapy for an indolent B-cell lymphoma is allowed.
• Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
• Therefore, for women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required.
• Age 18 - 80 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
• Absolute neutrophil count (ANC) >= 1,000/mm\^3.
• Unless attributable to lymphoma.
• Platelet count >= 100,000/mm\^3.
• Unless attributable to lymphoma.
• Creatinine =< 1.5 mg/dL OR calculated (calc.) creatinine clearance >= 50 mL/min.
• Unless attributable to lymphoma.
• Total bilirubin =< 2.0 mg/dL.
• Unless attributable to lymphoma.
• Unless attributable to Gilbert's disease.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 times institution upper limit of normal (ULN).
• Unless attributable to lymphoma.

Where it is running

• Anchorage Associates in Radiation Medicine — Anchorage, Alaska, United States
• Anchorage Radiation Therapy Center — Anchorage, Alaska, United States
• Alaska Breast Care and Surgery LLC — Anchorage, Alaska, United States
• Alaska Oncology and Hematology LLC — Anchorage, Alaska, United States
• Alaska Women's Cancer Care — Anchorage, Alaska, United States
• Anchorage Oncology Centre — Anchorage, Alaska, United States
• Katmai Oncology Group — Anchorage, Alaska, United States
• Providence Alaska Medical Center — Anchorage, Alaska, United States
• Fairbanks Memorial Hospital — Fairbanks, Alaska, United States
• Cancer Center at Saint Joseph's — Phoenix, Arizona, United States
• Mercy Hospital Fort Smith — Fort Smith, Arkansas, United States
• CHI Saint Vincent Cancer Center Hot Springs — Hot Springs, Arkansas, United States
• Mission Hope Medical Oncology - Arroyo Grande — Arroyo Grande, California, United States
• Providence Saint Joseph Medical Center/Disney Family Cancer Center — Burbank, California, United States
• Community Cancer Institute — Clovis, California, United States
• University Oncology Associates — Clovis, California, United States
• Loma Linda University Medical Center — Loma Linda, California, United States
• Fremont - Rideout Cancer Center — Marysville, California, United States
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States
• UCSF Medical Center-Parnassus — San Francisco, California, United States
• Pacific Central Coast Health Center-San Luis Obispo — San Luis Obispo, California, United States
• Mission Hope Medical Oncology - Santa Maria — Santa Maria, California, United States
• Gene Upshaw Memorial Tahoe Forest Cancer Center — Truckee, California, United States
• Rocky Mountain Cancer Centers-Aurora — Aurora, Colorado, United States
• University of Alabama at Birmingham Cancer Center — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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