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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 04/16/2021.

Obinutuzumab, Venetoclax, and Lenalidomide in Treating Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Clinicaltrials.gov identifier NCT02992522

Recruitment Status Suspended (PI decsion)

First Posted December 14, 2016

Last update posted September 28, 2020

Study Description

Brief summary:

This phase I study studies the side effects and best dose of venetoclax and lenalidomide when given together with obinutuzumab in treating patients with B-cell non-Hodgkin lymphoma that has returned after a period of improvement or not responding to treatment. Monoclonal antibodies, such as obinutuzumab, may interfere with the ability of cancer cells to grow and spread. Venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as lenalidomide, 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 obinutuzumab, venetoclax, and lenalidomide may work better in treating patients with B-cell non-Hodgkin lymphoma.

  • Condition or Disease:Refractory Diffuse Large B-Cell Lymphoma
    Refractory Follicular Lymphoma
    Transformed Recurrent Non-Hodgkin Lymphoma
    B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma
    Grade 1 Follicular Lymphoma
    Grade 2 Follicular Lymphoma
    Recurrent Diffuse Large B-Cell Lymphoma
    Recurrent Follicular Lymphoma
    Recurrent Marginal Zone Lymphoma
    Refractory Burkitt Lymphoma
    Grade 3a Follicular Lymphoma
    Recurrent Burkitt Lymphoma
  • Intervention/Treatment: Drug: Lenalidomide
    Biological: Obinutuzumab
    Drug: Venetoclax
  • Phase: Phase 1
Detailed Description

PRIMARY OBJECTIVES: I. To determine the dose limiting toxicity (DLT) and the recommended phase 2 dose (RP2D), which is typically the maximum tolerated dose (MTD), of the combination of obinutuzumab, venetoclax, and lenalidomide in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). SECONDARY OBJECTIVES: I. To estimate the overall objective response rate to the combination of obinutuzumab, venetoclax, and lenalidomide in patients with relapsed or refractory B-cell NHL. II. To estimate the duration of response and 2 year progression-free survival associated with obinutuzumab, venetoclax, and lenalidomide treatment in patients with relapsed and refractory B-cell NHL. III. To define the qualitative and quantitative toxicities of the combination of obinutuzumab, venetoclax, and lenalidomide in patients with relapsed or refractory B-cell NHL. OUTLINE: This is a dose-escalation study of venetoclax and lenalidomide. Patients receive lenalidomide orally (PO) on days 1-21 and venetoclax PO on days 1-28. Patients also receive obinutuzumab intravenously (IV) on days 1, 8, and 15 of course 1 and on day 1 of courses 2-6. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 4 weeks, every 3 months for 2 years, then every 6 months.

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 60 participants
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: A Phase I Study of Obinutuzumab, Venetoclax, and Lenalidomide in Relapsed and Refractory B-cell Non-Hodgkin Lymphoma
  • Actual Study Start Date: February 2017
  • Estimated Primary Completion Date: December 2020
  • Estimated Study Completion Date: January 2021
Arms and interventions
Arm Intervention/treatment
Experimental: Treatment (lenalidomide, venetoclax, obinutuzumab)
Patients receive lenalidomide PO on days 1-21 and venetoclax PO on days 1-28. Patients also receive obinutuzumab IV on days 1, 8, and 15 of course 1, and day 1 of courses 2-6. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Drug: Lenalidomide
Given PO

Biological: Obinutuzumab
Given IV

Drug: Venetoclax
Given PO
Outcome Measures
  • Primary Outcome Measures: 1. MTD defined as the highest level at which no more than 6 patients experience a DLT assessed by National Cancer Institute Common Terminology Criteria of Adverse Events version 4 [ Time Frame: Up to 28 days ]
    The recommended phase 2 dose (RP2D), which is typically the maximum tolerated dose (MTD), of the combination of obinutuzumab, venetoclax, and lenalidomide in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL).
  • Secondary Outcome Measures: 1. Objective response rate (ORR) defined as the proportion of patients achieving a complete or partial, response according to the Lugano Lymphoma Response Criteria [ Time Frame: Up to 3 years ]
    ORR will be reported with a 95% binomial confidence interval.
  • 2. Progression-free survival [ Time Frame: From course 1 day 1 to the date of the event (i.e., death or disease progression), assessed up to 2 years ]
    PFS will be estimated using the method of Kaplan-Meier. Median PFS and 2-year PFS estimates will be reported with 95% confidence intervals. If applicable, a sensitivity analysis of PFS will include any eligible patient who receives at least one dose of study treatment (i.e. venetoclax alone without beginning the combination regimen).
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Prior venetoclax or other BCL-2 family inhibitors or prior lenalidomide is not
permitted

- Creatinine clearance >= 50 ml/min using a 24 hour creatinine clearance or estimated
creatinine clearance using the Cockcroft-Gault equation

- Bilirubin =< 1.5 x upper limit of normal (ULN) unless due to Gilbert's syndrome - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) == 1000/mm^3

- Platelet >= 75,000/mm^3

- Unless related to bone marrow involvement with disease, in which case platelets
must be >= 50,000/mm^3

- Recovery to = 1.5 cm in size or assessable disease

- All study participants must be registered into the mandatory Revlimid risk evaluation
and mitigation strategy (REMS) program, and be willing and able to comply with the
requirements of the REMS program

- Females of reproductive potential must adhere to the scheduled pregnancy testing as
required in the Revlimid REMS program

- Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients
intolerant to aspirin (ASA) may use low molecular weight heparin or equivalent)

- EXPANSION COHORT

- Cohort A will enroll 10 patients with a diagnosis of diffuse large B-cell lymphoma;
B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell
lymphoma and Burkitt lymphoma (double hit lymphoma), Burkitt lymphoma, and transformed
lymphoma

- Cohort B will enroll 20 patients with a diagnosis of follicular lymphoma, grade 1-2
and 3A; grade 3B is excluded; diagnoses made by a fine needle aspirate or bone marrow
biopsy alone are not permitted

Exclusion Criteria:

- Patients with active central nervous system (CNS) involvement with lymphoma are not
eligible

- Patients with human immunodeficiency virus (HIV) or human T-cell leukemia virus 1
(HTLV-1) are not eligible

- Evidence of active hepatitis B infection, based on positive surface antigen or
hepatitis B deoxyribonucleic acid (DNA) polymerase chain reaction (PCR), or active
hepatitis C infection; patients who are hepatitis B core antibody positive must take
prophylaxis with lamivudine or equivalent and be willing to undergo monthly hepatitis
B DNA PCR testing

- Prior allogeneic stem cell transplant is not permitted

- Unable to swallow capsules or malabsorption syndrome, disease significantly affecting
gastrointestinal function, or resection of the stomach or small bowel or ulcerative
colitis, symptomatic inflammatory bowel disease, or partial or complete bowel
obstruction likely to interfere with the delivery, absorption, or metabolism of
venetoclax or lenalidomide

- Any chemotherapy or radiation therapy within 4 weeks of the first dose of study drug

- Patients may take steroids for disease control up to 24 hours prior to study
enrollment

- Any illness, medical condition or organ system dysfunction which, in the
investigator's opinion, could compromise the subject's safety, interfere with the
absorption or metabolism of venetoclax and lenalidomide, or put the study outcomes at
undue risk

- A cardiovascular disability status of New York Heart Association class >= 2

- History of severe allergic reactions to humanized monoclonal antibodies

- 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 or stage 1 melanoma of the skin or in situ carcinoma of the
cervix are eligible; patients with a malignancy that has been treated with surgery
alone with curative intent will also be excluded; individuals in documented remission
without treatment for >= 2 years prior to enrollment may be included at the discretion
of the investigator

- Known hypersensitivity to any of the study drugs or analogs

- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
(excluding fungal infections of nail beds) at study enrollment, or any major episode
of infection requiring treatment with IV antibiotics or hospitalization (relating to
the completion of the course of antibiotics) within 4 weeks prior study therapy

- Requires the use of warfarin (because of potential drug-drug interactions that may
potentially increase the exposure of warfarin)

- Received the following agents within 7 days prior to the first dose of venetoclax:

- Strong and moderate CYP3A inhibitors

- Strong and moderate CYP3A inducers

- Consumed grapefruit, grapefruit products, Seville oranges (including marmalade
containing Seville oranges), or star fruit within 3 days prior to the first dose
of venetoclax

- Clinically significant history of liver disease, including viral or other hepatitis,
current alcohol abuse, or cirrhosis

- Receipt of live-virus vaccines within 28 days prior to the initiation of study
treatment or need for live-virus vaccines at any time during study treatment

- Recent major surgery (within 6 weeks prior to the start of study treatment) other than
for diagnosis

- Malabsorption syndrome or other condition that precludes enteral route of
administration

- Known allergy to both xanthine oxidase inhibitors and rasburicase

- Pregnant or lactating, or intending to become pregnant during the study

Contacts and Locations
Contacts
Locations

United States, Georgia
Emory University
Atlanta

United States, Ohio
Ohio State University Comprehensive Cancer Center
Columbus

Sponsors and Collaborators

Beth Christian

Celgene

Genentech, Inc.

Investigators

Principal Investigator: Beth Christian, MD Ohio State University Comprehensive Cancer Center

More Information
  • Responsible Party: Beth Christian
  • ClinicalTrials.gov Identifier: NCT02992522 History of Changes
  • Other Study ID Numbers: OSU-16187, NCI-2016-01723
  • First Posted: December 14, 2016 Key Record Dates
  • Last Update Posted: September 28, 2020
  • Last Verified: September 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: No
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Additional relevant MeSH terms: Burkitt Lymphoma
    Lymphoma
    Lymphoma, Follicular
    Lymphoma, Non-Hodgkin
    Lymphoma, B-Cell
    Lymphoma, Large B-Cell, Diffuse