Glofitamab With Obinutuzumab, Venetoclax, and Lenalidomide for the Treatment of Patients With Newly Diagnosed High Risk Mantle Cell Lymphoma

NCT05861050 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 22685NCI-2023-03181P30CA033572
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I/II trial tests the safety and effectiveness of glofitamab (with obinutuzumab pretreatment), venetoclax, and lenalidomide in treating patients with newly diagnosed, high risk mantle cell lymphoma. Glofitamab and obinutuzumab are monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Lenalidomide works by helping the immune system kill cancer cells and by helping the bone marrow to produce normal blood cells. Giving venetoclax, glofitamab with obinutuzumab, and lenalidomide together may kill more cancer cells in patients with newly diagnosed, high risk mantle cell lymphoma.

Conditions

Blastoid Variant Mantle Cell Lymphoma; Mantle Cell Lymphoma; Pleomorphic Variant Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Progression free survival (PFS)

  From first dose of combination lenalidomide, venetoclax, and glofitamab to the occurrence of definitive disease progression or death from any cause, assessed up to 24 months

• Incidence of dose limiting toxicity

  Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

  Up to 63 days after initiation of venetoclax

Secondary Outcomes (5)

• Incidence of adverse events of special interest

  From baseline up until 30 days after last dose of study drug

• Median (or mean) PFS

  From the first dose of the combination of lenalidomide, venetoclax, and glofitamab to the occurrence of definitive disease progression or death from any cause, whichever comes first, assessed up to 5 years

• Best overall response

  Until disease progression or at 1 year after initiating therapy, whichever is sooner

• Minimal residual disease status

  At the end of 12 cycles of treatment (each cycle is 28 days)

• Duration of response

  From the time of initial response until disease progression or death due to any cause, whichever occurs first, assessed up to 2 years

Study Arms (1)

Treatment (venetoclax, glofitamab, lenalidomide)

EXPERIMENTAL

Patients receive venetoclax PO, obinutuzumab IV, glofitamab IV, and lenalidomide IV on study. Patients undergo bone marrow biopsy, blood sample collection, and CT scan and/or PET scan throughout the study. Patients may undergo tumor biopsy throughout the study.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Biological: Glofitamab; Drug: Lenalidomide; Biological: Obinutuzumab; Procedure: Positron Emission Tomography; Drug: Venetoclax

Interventions

Biopsy PROCEDURE

Undergo tumor biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (venetoclax, glofitamab, lenalidomide)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (venetoclax, glofitamab, lenalidomide)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (venetoclax, glofitamab, lenalidomide)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (venetoclax, glofitamab, lenalidomide)

Glofitamab BIOLOGICAL

Given IV

Also known as: Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody RO7082859, RO 7082859, RO7082859

Treatment (venetoclax, glofitamab, lenalidomide)

Lenalidomide DRUG

Given PO

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

Treatment (venetoclax, glofitamab, lenalidomide)

Obinutuzumab BIOLOGICAL

Given IV

Also known as: Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva, huMAB(CD20), R7159, RO 5072759, RO-5072759, RO5072759

Treatment (venetoclax, glofitamab, lenalidomide)

Positron Emission Tomography PROCEDURE

Undergo PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (venetoclax, glofitamab, lenalidomide)

Venetoclax DRUG

Given PO

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

Treatment (venetoclax, glofitamab, lenalidomide)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: \>= 18 to 80 years
• Eastern Cooperative Oncology Group =\< 2
• Diagnosis of MCL established by histologic assessment including one of the following:
• Immunohistochemistry of the biopsy
• Flow cytometry of the biopsy
• Evidence of t(11;14) translocation involving the cyclin D1 gene by fluorescence in situ hybridization (FISH), and/or cyclin D1 expression by immunohistochemistry (IHC) unless disease is morphologically consistent with MCL and has IHC expression of SOX11
• Requiring treatment for MCL, and for which no prior systemic anticancer therapies have been received
• Local radiotherapy not exceeding a total dose of 20 Gy at least 2 weeks prior the first dose of study therapy is allowed
• Laboratory, radiographic, physical exam findings and/or symptoms attributable to MCL
• Asymptomatic patients with blastoid or pleomorphic variant can be enrolled
• High risk features as classified by Jain et al.

You may not qualify if:

• Treatment with the use of warfarin (because of potential drug-drug interactions that may potentially increase the exposure of warfarin)
• Treatment with strong or moderate CYP3A inhibitors or strong CYP3A inducers within 4 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug. Consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to first dose of venetoclax
• Ongoing corticosteroid use \> 30 mg/day of prednisone or equivalent. Patients who received corticosteroid treatment with =\< 30 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to day 1 of cycle 1. Patients may have received a brief (=\< 7 days) course of systemic steroids (\>= 100 mg prednisone equivalent per day) prior to initiation of study therapy for control of lymphoma-related symptoms
• Corticosteroid therapy for control of cancer symptoms is permitted
• The use of inhaled corticosteroids is permitted
• The use of mineralocorticoids for management of orthostatic hypotension is permitted
• The use of physiologic doses of corticosteroids for management of adrenal insufficiency is permitted
• Illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment
• Prior solid organ transplantation within 60 months and requiring active immunosuppression
• Receipt of live-virus vaccine within 28 days prior to the initiation of the study treatment or need for live-virus vaccines at any time during the study treatment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents
• 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 low-grade, early-stage prostate cancer (Gleason score 6 or below, stage 1 or 2) with no requirement for therapy at any time prior to study are eligible
• Patients with any other malignancy appropriately treated with curative intent and the malignancy has been in remission without treatment for \>= 2 years prior to enrollment are eligible

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

Biopsy; Specimen Handling; glofitamab; Lenalidomide; obinutuzumab; Magnetic Resonance Spectroscopy; 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

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; 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; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Tycel J Phillips

  City of Hope Medical 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

Study Record Dates

• First Submitted: May 1, 2023
• First Posted: May 16, 2023
• Study Start: August 10, 2023
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: February 19, 2026

Record last verified: 2026-02

Locations

US (2)