Study of Venetoclax Plus DA-EPOCH-R for the Treatment of Aggressive B-Cell Lymphomas (V+DA-EPOCH-R)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03036904|
Recruitment Status : Active, not recruiting
First Posted : January 30, 2017
Last Update Posted : September 30, 2019
|Condition or disease||Intervention/treatment||Phase|
|Diffuse Large B-Cell Lymphoma High Grade B-Cell Lymphoma||Drug: Venetoclax Drug: Rituximab Drug: Etoposide Drug: Vincristine Sulfate Drug: Cyclophosphamide Drug: Prednisone Drug: Doxorubicin Hydrochloride||Phase 1|
This clinical trial is for men and women with aggressive B-Cell Lymphomas which includes:
- Diffuse large B-cell lymphoma (DLBCL),
- B-cell lymphoma unclassifiable with intermediate features between DLBCL and Burkitt Lymphoma (BL),
- High grade B-cell lymphoma (HGBCL),
- Transformed indolent NHL (TiNHL). The aggressive B-cell lymphomas enrolling on this study have been recognized to have a poor prognosis with the use of conventional chemoimmunotherapy. DA-EPOCH-R is an alternative highly effective chemoimmunotherapy platform for these lymphomas and may serve as an optimal chemotherapy backbone for the incorporation of novel agents such as venetoclax.
The Bcl-2 protein plays a significant role in the regulation of cell death in malignant cells. Overexpression of Bcl-2 family proteins is associated with chemo-resistance of a broad variety of cancers, and BCL2 abnormalities are common in aggressive B-cell Lymphomas. Venetoclax is a highly selective Bcl-2 family protein inhibitor that binds to Bcl-2 family proteins to potentially overcome resistance and enhance responses to therapy. This study has been designed to evaluate the safety and preliminary efficacy of venetoclax in combination with DA-EPOCH-R.
Subjects will receive venetoclax in conjunction with six 21-day cycles of DA-EPOCH-R. Dosing for DA-EPOCH-R will follow established protocols. Venetoclax will be administered on days 3 through 12 during cycle 1 and days 1 through 10 of each subsequent cycle. Following completion of therapy, subjects will be followed every three months for up to two years. Subjects removed from study due to toxicity will be followed until resolution or stabilization of the toxicity.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||34 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of Venetoclax Plus DA-EPOCH-R for the Treatment of Aggressive B-Cell Lymphomas|
|Actual Study Start Date :||February 6, 2017|
|Actual Primary Completion Date :||July 8, 2019|
|Estimated Study Completion Date :||August 2020|
Experimental: Venetoclax plus DA-EPOCH-R
Venetoclax will be given in conjunction with 6 cycles of DA-EPOCH-R (doxorubicin hydrochloride, etoposide, vincristine sulfate, cyclophosphamide, prednisone, rituximab). The dosing schedule and regimen for DA-EPOCH-R will follow established protocols. Venetoclax will be administered days 1-10 of each 21-day cycle, with the exception of cycle 1, during which venetoclax dose will commence on day 3 and continue through day 12, so as to clarify attribution of any observed TLS and/or infusion reactions, and minimize tumor lysis syndrome (TLS) risk.
Venetoclax will be administered orally on days 3-12 in cycle 1, and days 1-10 with all subsequent cycles except dose level -1. If dose level -1 is required, venetoclax will be administered on days 3-7 in cycle 1 and 1-5 with subsequent cycles.
Other Name: Venclexta
Rituximab will be administered as an IV infusion at 375 mg/m2 on day 1 of each cycle of DA-EPOCH-R, immediately prior to the start of chemotherapy. Oral pre-medication 650 mg of acetaminophen and 50-100 mg diphenhydramine hydrochloride will be administered 30 to 60 minutes prior to starting each infusion of rituximab. The first rituximab infusion should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr. If this rate of escalation is well tolerated the second and subsequent infusions can begin at a rate of 100 mg/hr and increase in 100 mg/hr increments every 30 minutes to a maximum of 400 mg/hr. CAUTION: DO NOT ADMINISTER AS AN INTRAVENOUS PUSH OR BOLUS.
Etoposide will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.
Drug: Vincristine Sulfate
Vincristine Sulfate will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.
Cyclophosphamide will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.
Other Name: cytoxan
Prednisone will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. Prednisone will be given orally.
Drug: Doxorubicin Hydrochloride
Doxorubicin Hydrochloride will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.
- Determination of the maximal tolerated dose (MTD) [ Time Frame: Approximately 24 months ]Determination of the maximal tolerated dose (MTD)
- Determination of dose limiting toxicity (DLT) [ Time Frame: Approximately 24 months ]Determination of dose limiting toxicity (DLT)
- Define incidence and severity of adverse events, defined according to CTCAE v 4.0. [ Time Frame: Approximately 24 months ]Define incidence and severity of adverse events, defined according to CTCAE v 4.0.
- Overall response rate [ Time Frame: Approximately 24 months ]Overall response rate
- Complete response rate [ Time Frame: Approximately 24 months ]Complete response rate
- Event-free survival [ Time Frame: Approximately 24 months ]Event-free survival
- Progression Free Survival [ Time Frame: Approximately 24 months ]Progression Free Survival
- Overall survival [ Time Frame: Approximately 24 months ]Overall survival
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03036904
|United States, Massachusetts|
|Massachusetts General Hospital Cancer Center|
|Boston, Massachusetts, United States, 02284|
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|Weill Cornell Medicine|
|New York, New York, United States, 10065|
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|United States, Pennsylvania|
|Fox Chase Cancer Center|
|Philadelphia, Pennsylvania, United States, 19111|
|United States, Texas|
|MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Study Chair:||John P. Leonard, M.D.||Weill Cornell Medicine|
|Study Chair:||Jeremy S. Abramson, M.D.||Massachusetts General Hospital|
|Principal Investigator:||Sarah Rutherford, M.D.||Weill Cornell Medicine|