Last updated on July 2020

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


Are you eligible to participate in this study?

You may be eligible for this study if you meet the following criteria:

  • Conditions: Diffuse Large B-Cell Lymphoma | Double Expressor Lymphoma | High Grade B-Cell Lymphoma | Not Otherwise Specified | Neoplastic Cells With Double Expression of MYC and BCL2 Proteins Present | High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements | Double-Expressor Lymphoma
  • Age: Between 18 - 100 Years
  • Gender: Male or Female

Inclusion Criteria:

  • Pathologic diagnosis of diffuse large B-cell lymphoma (DLBCL) or high grade B-cell lymphoma (HGBCL).
  • 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). (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 available in order to determine eligibility if enrolling as DEL based on local results
  • 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. Given the heterogeneity in diagnostic work-up and interpretation, all local determinations will be followed by central confirmation in real time. Diagnostic slides and stains (or recuts/blocks) from all cases will be submitted to a central reference laboratory (Cleveland Clinic Laboratories). Immunostains will be reviewed or repeated (if unavailable or technically unsatisfactory) to confirm double expressing (DE) status. All DE cases will also be investigated for double hit (DH) status, if not already performed. To exclude DHL status, FISH for translocations of MYC (break apart and IGH/MYC dual fusion probes) must be performed (either by referring site or at the central laboratory), along with BCL2 (break apart probes) and BCL6 (break apart probes). Any missing information from the referring site will be supplemented by the central lab on required submitted unstained slides or blocks. Cases submitted as DHL will be accepted as such upon review of submitted laboratory reports. 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 a MYC translocation by FISH.
  • 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. 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.
  • 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.

  • 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.
  • Archival tissue must be available for submission in all patients for histopathology review, though participation in correlative substudies is optional.
  • No active ischemic heart disease or congestive heart failure, and left ventricular ejection fraction (LVEF) >= 45%.
  • No known active human immunodeficiency virus (HIV) disease. Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
  • No known lymphomatous involvement of the central nervous system (CNS). A lumbar puncture or neuroimaging prior to study enrollment is not required in the absence of neurological signs or symptoms concerning for CNS involvement.
  • No active hepatitis B or hepatitis C infection. Patients with prior hepatitis B virus (HBV) exposure (positive HBV core antibody and/or surface antigen) are eligible if they have no detectable viral load, and are taking appropriate prophylactic antiviral therapy to prevent reactivation. Patients with history of hepatitis C virus (HCV) are eligible if they have been treated for HCV and have an undetectable HCV viral load.
  • Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to initiation of protocol therapy.
  • Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment.

Recruitment Status: Open


Brief Description Eligibility Contact Research Team


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