NCT03036904

Study of Venetoclax Plus DA-EPOCH-R for the Treatment of Aggressive B-Cell Lymphomas

Phase I Study of Venetoclax Plus DA-EPOCH-R for the Treatment of Aggressive B-Cell Lymphomas

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 31 (actual)
• Sponsor: Weill Medical College of Cornell University · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

This is a phase I, open label, single-arm, multi-center, dose-finding study of venetoclax in combination with DA-EPOCH-R in patients with aggressive B-Cell Lymphomas.

Detailed description

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.

Conditions

• Diffuse Large B-Cell Lymphoma
• High Grade B-Cell Lymphoma

Interventions

Type	Name	Description
DRUG	Venetoclax	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.
DRUG	Rituximab	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.
DRUG	Etoposide	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.
DRUG	Cyclophosphamide	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.
DRUG	Prednisone	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.

Timeline

• Start date: 2017-02-06
• Primary completion: 2021-11-11
• Completion: 2021-11-11
• First posted: 2017-01-30
• Last updated: 2022-08-24

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study