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

  • STATUS
    Recruiting
  • End date
    Apr 1, 2028
  • participants needed
    374
  • sponsor
    National Cancer Institute (NCI)
Updated on 5 March 2021
Investigator
Site Public Contact
Primary Contact
MercyOne Waterloo Medical Center (2.7 mi away) Contact
+510 other location
platelet count
cancer
cyclophosphamide
rituximab
vincristine
prednisone
gilbert's syndrome
etoposide
doxorubicin
venetoclax
neutrophil count
b-cell lymphoma
high grade b-cell lymphoma
da-epoch

Summary

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.

Description

PRIMARY OBJECTIVE:

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 1 or Arm 2.

ARM 1 (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 1 (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 2 (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.

ARM 2 (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.

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.

Details
Condition Diffuse Large B-Cell Lymphoma, Double-Expressor Lymphoma, 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, Double-Expressor Lymphoma, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade B-Cell Lymphoma, Not Otherwise Specified, Double-Expressor Lymphoma, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade B-Cell Lymphoma, Not Otherwise Specified, Double Expressor Lymphoma, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade 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, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade B-Cell Lymphoma, Not Otherwise Specified, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, diffuse large cell lymphoma, diffuse large b cell lymphoma, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, 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
Treatment Rituximab, cyclophosphamide, doxorubicin hydrochloride, etoposide, prednisone, vincristine sulfate, vincristine, doxorubicin, venetoclax
Clinical Study IdentifierNCT03984448
SponsorNational Cancer Institute (NCI)
Last Modified on5 March 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Do you have any of these conditions: Double Expressor Lymphoma or Diffuse Large B-Cell Lymphoma, Not Otherwise Specified or Double-Expressor Lymphoma or diffuse large b cell lymphoma or E...?
Do you have any of these conditions: Double-Expressor Lymphoma or Diffuse Large B-Cell Lymphoma, Not Otherwise Specified or EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Speci...?
Do you have any of these conditions: High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements or High Grade B-Cell Lymphoma, Not Otherwise Specified or Diffuse Large B-Cell Lym...?
Do you have any of these conditions: Diffuse Large B-Cell Lymphoma, Not Otherwise Specified or EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified or Neoplastic Cells With...?
Do you have any of these conditions: Double-Expressor Lymphoma or EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified or Diffuse Large B-Cell Lymphoma or High Grade B-Cell...?
Do you have any of these conditions: diffuse large cell lymphoma or Neoplastic Cells With Double Expression of MYC and BCL2 Proteins Present or High Grade B-Cell Lymphoma With MYC and BCL...?
Do you have any of these conditions: diffuse large cell lymphoma or Diffuse Large B-Cell Lymphoma, Not Otherwise Specified or High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrang...?
Do you have any of these conditions: EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified or diffuse large b cell lymphoma or diffuse large cell lymphoma or Double-Expresso...?
Do you have any of these conditions: Diffuse Large B-Cell Lymphoma, Not Otherwise Specified or diffuse large cell lymphoma or Double Expressor Lymphoma or Neoplastic Cells With Double Exp...?
Do you have any of these conditions: diffuse large cell lymphoma or Diffuse Large B-Cell Lymphoma or diffuse large b cell lymphoma or Diffuse Large B-Cell Lymphoma, Not Otherwise Specifie...?
Do you have any of these conditions: Diffuse Large B-Cell Lymphoma or High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements or Double-Expressor Lymphoma or EBV-Positive Diff...?
Do you have any of these conditions: EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified or diffuse large b cell lymphoma or Diffuse Large B-Cell Lymphoma or Diffuse Large...?
Do you have any of these conditions: diffuse large b cell lymphoma or EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified or Diffuse Large B-Cell Lymphoma or diffuse large...?
Do you have any of these conditions: Diffuse Large B-Cell Lymphoma or diffuse large b cell lymphoma or Diffuse Large B-Cell Lymphoma, Not Otherwise Specified or High Grade B-Cell Lymphoma...?
Do you have any of these conditions: Diffuse Large B-Cell Lymphoma or Neoplastic Cells With Double Expression of MYC and BCL2 Proteins Present or Double Expressor Lymphoma or Double-Expre...?
Is your age greater than or equal to 18 yrs?
Do you have any of these conditions: High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements or Neoplastic Cells With Double Expression of MYC and BCL2 Proteins Present or EBV...?
Do you have any of these conditions: diffuse large cell lymphoma or Double Expressor Lymphoma or Diffuse Large B-Cell Lymphoma or Neoplastic Cells With Double Expression of MYC and BCL2 P...?
Do you have any of these conditions: Diffuse Large B-Cell Lymphoma or Neoplastic Cells With Double Expression of MYC and BCL2 Proteins Present or EBV-Positive Diffuse Large B-Cell Lymphom...?
Do you have any of these conditions: Diffuse Large B-Cell Lymphoma, Not Otherwise Specified or EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified or High Grade B-Cell Lym...?
Do you have any of these conditions: Neoplastic Cells With Double Expression of MYC and BCL2 Proteins Present or High Grade B-Cell Lymphoma, Not Otherwise Specified or Double-Expressor Ly...?
Do you have any of these conditions: Neoplastic Cells With Double Expression of MYC and BCL2 Proteins Present or Double-Expressor Lymphoma or Double Expressor Lymphoma or High Grade B-Cel...?
Do you have any of these conditions: High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements or Diffuse Large B-Cell Lymphoma, Not Otherwise Specified or High Grade B-Cell Lym...?
Do you have any of these conditions: Double-Expressor Lymphoma or diffuse large cell lymphoma or diffuse large b cell lymphoma or High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rear...?
Do you have any of these conditions: Diffuse Large B-Cell Lymphoma, Not Otherwise Specified or High Grade B-Cell Lymphoma, Not Otherwise Specified or Double-Expressor Lymphoma or Double E...?
Do you have any of these conditions: EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified or High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements or Diffuse ...?
Do you have any of these conditions: EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified or Double Expressor Lymphoma or High Grade B-Cell Lymphoma With MYC and BCL2 or BC...?
Do you have any of these conditions: EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified or Double Expressor Lymphoma or Diffuse Large B-Cell Lymphoma, Not Otherwise Speci...?
Gender: Male or Female
Pathologic diagnosis of diffuse large B-cell lymphoma (DLBCL) or high grade B-cell lymphoma (HGBCL). Eligible subtypes include DLBCL not otherwise specified (NOS), Epstein Barr Virus positive (EBV+) DLBCL, 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). (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. 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
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 venetoclax
Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of venetoclax
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