An Early Phase Study of Venetoclax, Lenalidomide, and Rituximab/Hyaluronidase in Slow-Growing Lymphomas That Have Come Back After Treatment or Have Not Responded to Treatment

NCT04447716 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 19P.835JT 14408
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of venetoclax when given together with lenalidomide and rituximab hyaluronidase in treating patients with follicular lymphoma and marginal zone lymphoma that has come back after treatment (relapsed) or has not responded to treatment (refractory). Venetoclax may stop the growth of cancer cells by blocking the action of a protein called Bcl-2, that helps cancer cells survive. Immunotherapy with lenalidomide, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Immunotherapy with monoclonal antibodies, such as rituximab and rituximab hyaluronidase, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The purpose of this research is to determine if the combination of three drugs, venetoclax, lenalidomide, and rituximab hyaluronidase are safe to administer in patients whose low-grade lymphoma (follicular or marginal zone) has come back after initial therapy or was not responsive to initial therapy.

Conditions

Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Follicular Lymphoma; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Follicular Lymphoma; Refractory Indolent Adult Non-Hodgkin Lymphoma; Refractory Marginal Zone Lymphoma

Outcome Measures

Primary Outcomes (1)

• Rate of dose-limiting toxicities

  Toxicity incidences assessed and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0, will be tabulated by patient cohort.

  During the first 56 days of therapy

Secondary Outcomes (3)

• Overall response rate

  At the end of 12 month treatment period

• Progression-free survival (PFS)

  Time from study registration to documented disease progression or death from any cause, assessed at 2 years

• Overall survival (OS)

  Time from study registration to death from any cause, assessed at 2 years

Other Outcomes (4)

• Level of expression and expression ratio between anti-apoptotic and pro-apoptotic BCL-2 family proteins measured by flow cytometry and messenger ribonucleic acid (mRNA)

  42 days of starting treatment through end of treatment

• Metabolic landscape

  42 days of screening through until end of treatment

• Immune profile

  42 days of starting treatment through until end of treatment

Study Arms (1)

Treatment (venetoclax, lenalidomide, rituximab, hyaluronidase)

EXPERIMENTAL

Patient receive venetoclax PO QD on days 1-28. Beginning cycle 2, patients receive lenalidomide PO QD on days 1-21. Patients also receive rituximab IV on days 1, 8, 15, and 22 of cycle 2 and rituximab hyaluronidase (if no significant infusion reaction to rituximab) SC on day 1 of cycles 4, 6, 8, 10, and 12. Patients may receive rituximab IV (instead of rituximab hyaluronidase) on days 1, 8, 15, and 22 of cycles 4, 6, 8, 10, and 12 if the patient requires rituximab IV in the opinion of the treating physician. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Venetoclax; Drug: Lenalidomide; Biological: Rituximab; Biological: Rituximab and Hyaluronidase Human

Interventions

Venetoclax DRUG

Given PO

Also known as: 1257044-40-8,, 4-(4-((2-(4-Chlorophenyl)-4, 4-dimethylcyclohex-1-en-1-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(1H-pyrrolo(2,3-b)pyridin-5-yloxy)benzamide,, ABT-0199,, ABT-199,, ABT199,, RG7601,, GDC-0199,

Treatment (venetoclax, lenalidomide, rituximab, hyaluronidase)

Lenalidomide DRUG

Given PO

Also known as: 191732-72-6,, 3-(4-Amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione,, 703813,, CC-5013, Revlimid, CC5013, CDC 501,, lenalidomide,

Treatment (venetoclax, lenalidomide, rituximab, hyaluronidase)

Rituximab BIOLOGICAL

Given IV

Also known as: 174722-31-7,, 687451,, ABP 798,, BI 695500,, C2B8 Monoclonal Antibody,, Chimeric Anti-CD20 Antibody,, CT-P10,, IDEC-102,, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody,, MabThera,, Monoclonal Antibody IDEC-C2B8,, PF-05280586,, Rituxan,, Rituximab,, RITUX

Treatment (venetoclax, lenalidomide, rituximab, hyaluronidase)

Rituximab and Hyaluronidase Human BIOLOGICAL

Given SC

Also known as: Rituxan Hycela,, Rituximab Plus Hyaluronidase,, Rituximab/Hyaluronidase,, Rituximab/Hyaluronidase Human

Treatment (venetoclax, lenalidomide, rituximab, hyaluronidase)

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form
• Ability and willingness to comply with the requirements of the study protocol
• Able to swallow oral medications whole
• Patients must have received at least one prior systemic therapy
• Histologically confirmed indolent B-cell non-Hodgkin's lymphoma (NHL) of any of the following subtypes recognized by the World Health Organization (WHO) classification: Follicular lymphoma and marginal zone lymphoma. Patients with indolent non-Hodgkin's Lymphoma (iNHL) should have received at least 1 previous prior therapy
• Patients must have an indication for treatment by Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria 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
• All study participants must be registered into the mandatory lenalidomide 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 lenalidomide 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. Inability to take any form of prophylaxis excludes participation
• Eastern Cooperative Oncology Group performance status of 0, 1, or 2
• Hemoglobin \>= 9 g/dL (unless caused by underlying disease, as established by extensive bone marrow involvement or as a result of hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator)
• Absolute neutrophil count \>= 1.0 x 10\^9/L (unless caused by underlying disease, as established by extensive bone marrow involvement or as a result of hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator)
• Platelet count \>= 75 x 10\^9/L (unless caused by underlying disease, as established by extensive bone marrow involvement or as a result of hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator)
• International normalized ratio \> 1.5 x upper limit of normal (ULN) for patients not receiving therapeutic anticoagulation

You may not qualify if:

• Known hypersensitivity to any of the study drugs study drugs
• Known central nervous system (CNS) involvement by lymphoma
• Prior allogeneic stem cell transplant is not permitted if patient is fewer than 4 months from transplant and has either active graft versus host disease or on immunosuppression
• History of severe allergic reactions to humanized monoclonal antibodies
• Prior use of lenalidomide or venetoclax or other BCL2 family inhibitors; prior rituximab is allowed as long as they continue to express CD20 and are not rituximab refractory as defined as: \* Did not respond (at least a partial response \[PR\]) to rituximab or rituximab (R)-chemoregimen therapy \* Time to disease progression \< 6 months after last rituximab dose
• 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
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the patient, including renal disease that would preclude chemotherapy administration or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
• 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 to registration
• 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 registration: \* Steroid therapy for anti-neoplastic intent \* 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 Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg), or hepatitis C (HCV) antibody \* Patients who are positive for HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible for study participation \* Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody \[HBcAb\] and negative HBsAg) may be included if HBV deoxyribonucleic acid (DNA) is undetectable. These patients must be willing to undergo monthly DNA testing.
• Known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus 1 (HTLV-1)
• 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
• Pregnant or lactating, or intending to become pregnant during the study
• Recent major surgery (within 6 weeks prior to the start of cycle 1, day 1) other than for diagnosis

Sponsors & Collaborators

• Thomas Jefferson University: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone

Interventions

venetoclax; Lenalidomide; Rituximab; CT-P10; Hyaluronoglucosaminidase

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

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; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Polysaccharide-Lyases; Carbon-Oxygen Lyases; Lyases

Study Officials

• Ubaldo R Martinez-Outschoorn, MD

  Thomas Jefferson University

  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

Study Record Dates

• First Submitted: April 9, 2020
• First Posted: June 25, 2020
• Study Start: October 16, 2020
• Primary Completion: May 16, 2024
• Study Completion (Estimated): April 1, 2027
• Last Updated: September 15, 2025

Record last verified: 2025-09

Locations

US (1)