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

NCT02992522 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-16187NCI-2016-01723
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

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.

Conditions

B-Cell Lymphoma, Unspecified; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma; B-Cell

Outcome Measures

Primary Outcomes (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

  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).

  Up to 28 days

Secondary Outcomes (2)

• Objective response rate (ORR) defined as the proportion of patients achieving a complete or partial, response according to the Lugano Lymphoma Response Criteria

  Up to 3 years

• Progression-free survival

  From course 1 day 1 to the date of the event (i.e., death or disease progression), assessed up to 2 years

Study Arms (1)

Treatment (lenalidomide, venetoclax, obinutuzumab)

EXPERIMENTAL

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; Biological: Obinutuzumab; Drug: Venetoclax

Interventions

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

Treatment (lenalidomide, venetoclax, obinutuzumab)

Obinutuzumab BIOLOGICAL

Given IV

Also known as: Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva, huMAB(CD20), R7159, RO 5072759

Treatment (lenalidomide, venetoclax, obinutuzumab)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta

Treatment (lenalidomide, venetoclax, obinutuzumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) =\< 3 x ULN
• Absolute neutrophil count (ANC) \>= 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 =\< grade 1 from all toxicities associated with prior therapy except alopecia
• Histologically confirmed B-cell non-Hodgkin's lymphoma (NHL) of any of the following subtypes recognized by the World Health Organization (WHO) classification: Burkitt lymphoma, B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, diffuse large B-cell lymphoma, marginal zone lymphoma, or follicular lymphoma; patients with evidence of histological transformation to diffuse large B-cell lymphoma from indolent NHL are eligible
• At least one prior therapy; prior autologous stem cell transplant is permitted; patients with aggressive lymphoma who have not received high-dose therapy (HDT)/autologous stem cell transplantation (ASCT) must be ineligible for HDT/ASCT; prior allogeneic stem cell transplant is not permitted
• Patients with indolent lymphoma must have an indication for treatment in the opinion of the investigator
• Radiographically measurable disease by computed tomography (CT) scan, defined as at least one node \> 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Beth Christian: lead
• Celgene: collaborator
• Genentech, Inc.: collaborator

Study Sites (2)

Emory University

Atlanta, Georgia, 30322, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, Follicular; Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, B-Cell, Marginal Zone

Interventions

Lenalidomide; obinutuzumab; venetoclax

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Beth Christian, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 12, 2016
• First Posted: December 14, 2016
• Study Start: February 21, 2017
• Primary Completion (Estimated): August 15, 2026
• Study Completion (Estimated): August 15, 2026
• Last Updated: September 9, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)