CompletedNCT03036904V+DA-EPOCH-RUpdated Aug 24, 2022

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

A Phase 1 interventional study of Venetoclax and Rituximab in Diffuse Large B-Cell Lymphoma and High Grade B-Cell Lymphoma, sponsored by Weill Medical College of Cornell University. Completed at 6 sites in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2022-08-24.

Sponsored by Weill Medical College of Cornell University · Phase 1, Interventional, and Treatment

From the registry’s dates

Primary completion was Nov 2021, 4 years 10 months ago, and no results have been posted to the registry.

Phase: Phase 1
Study type: Interventional
Enrollment: 31
Allocation: Not applicable
Ages: 18 Years to 80 Years
Sex: All

Study 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.

Read the 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 studied

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

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Keywords

venetoclax
dose-adjusted EPOCH-R
aggressive B-Cell lymphoma
Lymphoma
Non-Hodgkin lymphoma
Diffuse large B-cell lymphoma
Double hit lymphoma

In context

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 31 is below the median of 40 across 4,508 interventional studies indexed under Lymphoma.

Browse Lymphoma studies →

Lead sponsor

Weill Medical College of Cornell University is the lead sponsor of 867 studies on the registry; 160 are open to participants now.

Of its 119 completed or terminated interventional studies of FDA-regulated products, 91 (76%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 80 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Adults age 18-80 years
Histologically confirmed, biopsy-proven diagnosis of DLBCL, BCLu, HGBCL, or TiNHL.

Richter's transformation from Chronic Lymphocytic Leukemia (CLL) is not eligible.

Subjects with DLBCL, BCLu, HGBCL NOS, or HGBCL with translocations of MYC and BCL2 and/or BCL6, must have had no prior chemotherapy for lymphoma. Steroids for palliation prior to enrollment are allowed.
Subjects with TiNHL are eligible if they have received no prior cytotoxic chemotherapy for lymphoma. Steroids, rituximab, and external beam radiation therapy as prior therapy for indolent lymphoma is allowed.
Ann Arbor stage II-IV disease (Stage I primary mediastinal B-cell lymphoma will also be eligible)
Ability to provide signed Informed Consent Form
Ability and willingness to comply with the requirements of the study protocol
Measureable disease (defined as at least 1.5 cm in diameter).
Adequate organ and bone marrow function:
Absolute neutrophil count (ANC) at least 1,000/mm3
Platelet count at least 100,000/mm3.
Total bilirubin at most1.5 x the upper limit of the normal range (ULN), except Gilbert's disease
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at most 3 x ULN.
Calculated creatinine clearance at least 30 mL/min.

Exclusion criteria

Exclusion criteria:

Known hypersensitivity to any of the study drugs
History of other malignancy that could affect compliance with the protocol or interpretation of results
Patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are generally eligible. Patients with a malignancy that has been treated, but not with curative intent, will also be excluded, unless the malignancy has been in remission without treatment for at least 2 years prior to enrollment.
Known CNS involvement at diagnosis
Richter's transformation from CLL
Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal)
Major surgery within 3 weeks prior to the start of study treatment
Infection with human immunodeficiency virus (HIV)
Women who are pregnant or lactating
Female patients who are not surgically sterile or postmenopausal (for at least 1 year) must practice at least one of the following methods of birth control throughout the duration of study participation and for at least 3 months after study treatment:
Total abstinence from sexual intercourse
A vasectomized partner
Hormonal contraceptives (oral, parenteral, vaginal ring, or transdermal) that started at least 3 months prior to study drug administration
Double-barrier method (condom plus diaphragm or cervical cup with spermicidal contraceptive sponge, jellies, or cream)
Non-vasectomized male patients must comply with at least one of the following methods of birth control throughout the duration of study participation and for at least 3 months after study treatment:
A partner who is surgically sterile or postmenopausal (for at least 1 year) or who is taking hormonal contraceptives (oral, parenteral, vaginal ring, or transdermal) for at least 3 months prior to study drug administration
Total abstinence from sexual intercourse
Double-barrier method (condom plus diaphragm or cervical cup with spermicidal, contraceptive sponge, jellies, or cream)
Malabsorption syndrome or other condition that precludes enteral route of administration
Known allergy to both xanthine oxidase inhibitors and rasburicase
Subjects with positive HBV core antibody or surface antigen are eligible as long as they have an undetectable HBV DNA PCR, and receive concurrent antiviral therapy with entecavir, tenofovir, or lamivudine, and continued for a minimum of 6 months after completion of therapy.
Active hepatitis C (defined as a positive HCV viral load)
Chronic use of moderate or strong CYP3A4 modulators (inhibitor or inducer) or any other prohibited medications. A washout period of 7 days is required prior to venetoclax dosing if a prohibited medication is discontinued.
Chronic use of a P-gp inhibitor, or a P-gp substrate with a narrow therapeutic index. A washout period of 7 days is required prior to venetoclax dosing if a prohibited medication is discontinued.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 31 participants (actual)

Study arms

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.
Drug: Venetoclax · Drug: Rituximab · Drug: Etoposide · Drug: Vincristine Sulfate · Drug: Cyclophosphamide · Drug: Prednisone · Drug: Doxorubicin Hydrochloride

Interventions

DrugVenetoclax
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.
Also known as: Venclexta
DrugRituximab
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.
Also known as: Rituxan, IDEC-C2B8, chimeric anti-CD20 monoclonal antibody
DrugEtoposide
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.
Also known as: VP-16, VePesid, etopophos, toposar
DrugVincristine 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.
Also known as: LCR, VCR
DrugCyclophosphamide
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.
Also known as: cytoxan
DrugPrednisone
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.
Also known as: Deltasone, Orasone, Paracort, Cortan
DrugDoxorubicin 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.
Also known as: Hydroxydaunomycin Hydrochloride, Hydroxydoxorubicin Hydrochloride

What researchers measure

Primary outcomes

Determination of the maximal tolerated dose (MTD)
Determination of the maximal tolerated dose (MTD)
Time frame: Approximately 24 months
Determination of dose limiting toxicity (DLT)
Determination of dose limiting toxicity (DLT)
Time frame: Approximately 24 months

Secondary outcomes

Define incidence and severity of adverse events, defined according to CTCAE v 4.0.
Define incidence and severity of adverse events, defined according to CTCAE v 4.0.
Time frame: Approximately 24 months
Overall response rate
Overall response rate
Time frame: Approximately 24 months
Complete response rate
Complete response rate
Time frame: Approximately 24 months
Event-free survival
Event-free survival
Time frame: Approximately 24 months
Progression Free Survival
Progression Free Survival
Time frame: Approximately 24 months
Overall survival
Overall survival
Time frame: Approximately 24 months

Study locations

6 sites

Massachusetts General Hospital Cancer Center
Boston, Massachusetts 02284, United States
Washington University School of Medicine
Saint Louis, Missouri 63110, United States
Weill Cornell Medicine
New York, New York 10065, United States
Ohio State University Medical Center
Columbus, Ohio 43210, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania 19111, United States
MD Anderson Cancer Center
Houston, Texas 77030, United States

References and documents

Publications

Rutherford SC, Abramson JS, Bartlett NL, Barta SK, Khan N, Joyce R, Maddocks K, Ali-Shaw T, Senese S, Yuan Y, Westin J, Leonard JP. Venetoclax with dose-adjusted EPOCH-R as initial therapy for patients with aggressive B-cell lymphoma: a single-arm, multicentre, phase 1 study. Lancet Haematol. 2021 Nov;8(11):e818-e827. doi: 10.1016/S2352-3026(21)00273-8. Epub 2021 Oct 8. PubMed 34634256 ↗

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 24, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03036904
Lead sponsor: Weill Medical College of Cornell University
Collaborators: Genentech, Inc., Massachusetts General Hospital, M.D. Anderson Cancer Center
Responsible party: Sponsor
First posted: Jan 30, 2017
Start date: Feb 6, 2017
Primary completion: Nov 11, 2021
Completion: Nov 11, 2021
Last update: Aug 24, 2022

Study contacts

John P. Leonard, M.D.

study chair · Weill Medical College of Cornell University

Jeremy S. Abramson, M.D.

study chair · Massachusetts General Hospital

Sarah Rutherford, M.D.

principal investigator · Weill Medical College of Cornell University

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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