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Diffuse Large B-Cell LymphomaPhase 1V+DA-EPOCH-RNCT03036904

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

A Phase 1 study testing Venetoclax, Rituximab and Etoposide in people with Diffuse Large B-Cell Lymphoma and High Grade B-Cell Lymphoma, run by Weill Medical College of Cornell University at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Venetoclax, Rituximab and Etoposide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
6 sitesUnited States
Study dates
6 Feb 2017to 11 Nov 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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.

Who cannot join

  • 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)
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  • 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.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02284

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Weill Cornell Medicine

    New York, New York, 10065

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

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

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.

Keywords
venetoclax, dose-adjusted EPOCH-R, aggressive B-Cell lymphoma, Lymphoma, Non-Hodgkin lymphoma, Diffuse large B-cell lymphoma, Double hit lymphoma
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VenetoclaxDrug

    Also called Venclexta

    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.

  • RituximabDrug

    Also called Rituxan, IDEC-C2B8, chimeric anti-CD20 monoclonal antibody

    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.

  • EtoposideDrug

    Also called VP-16, VePesid, etopophos, toposar

    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.

  • Vincristine SulfateDrug

    Also called LCR, VCR

    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.

  • CyclophosphamideDrug

    Also called cytoxan

    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.

  • PrednisoneDrug

    Also called Deltasone, Orasone, Paracort, Cortan

    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.

  • Doxorubicin HydrochlorideDrug

    Also called Hydroxydaunomycin Hydrochloride, Hydroxydoxorubicin 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.

Study groups in NCT03036904
Study groupRoleWhat they receive
Venetoclax plus DA-EPOCH-RExperimentalVenetoclax 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.
Receives: Drug: Venetoclax; Drug: Rituximab; Drug: Etoposide; Drug: Vincristine Sulfate; Drug: Cyclophosphamide; Drug: Prednisone; Drug: Doxorubicin Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Determination of the maximal tolerated dose (MTD)

    Determination of the maximal tolerated dose (MTD)

    Measured: Approximately 24 months

  2. Determination of dose limiting toxicity (DLT)

    Determination of dose limiting toxicity (DLT)

    Measured: Approximately 24 months

Secondary outcomes (6)

  1. 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.

    Measured: Approximately 24 months

  2. Overall response rate

    Overall response rate

    Measured: Approximately 24 months

  3. Complete response rate

    Complete response rate

    Measured: Approximately 24 months

  4. Event-free survival

    Event-free survival

    Measured: Approximately 24 months

  5. Progression Free Survival

    Progression Free Survival

    Measured: Approximately 24 months

  6. Overall survival

    Overall survival

    Measured: Approximately 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jan 2017 (estimated)
  2. Study start6 Feb 2017
  3. Primary completion11 Nov 2021
  4. Study completion11 Nov 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03036904
Sponsor's protocol ID
1607017413
Acronym
V+DA-EPOCH-R
Status last verified
Aug 2022
First submitted
27 Jan 2017
Last updated
24 Aug 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Venetoclax, Rituximab and Etoposide in people with Diffuse Large B-Cell Lymphoma and High Grade B-Cell Lymphoma, run by Weill Medical College of Cornell University at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determination of the maximal tolerated dose (MTD) (time frame: Approximately 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03036904, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2022.

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