A Study of Glofitamab and Lenalidomide in People With Mantle Cell Lymphoma

Pilot Study of Glofitamab and Lenalidomide in Patients With Relapsed or Refractory Mantle Cell Lymphoma Previously Treated With a BTK Inhibitor

The purpose of this study is to find out whether the combination of glofitamab and lenalidomide is an effective treatment for relapsed or refractory Mantle Cell Lymphoma

Study Overview

• Status: Recruiting
• Conditions: Mantle Cell Lymphoma; MCL
• Intervention / Treatment: Drug: Glofitamab; Drug: Obinutuzumab; Drug: Lenalidomide

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Anita Kumar, MD; Phone Number: 646-608-3780; Email: kumara2@mskcc.org
• Study Contact Backup: Name: Gilles Salles, MD, PhD; Phone Number: 646-608-4153; Email: SallesG@mskcc.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Not yet recruiting
      • Dana Farber Cancer Institute (Data Collection and Specimen Analysis)
      • Contact: Christine Ryan, MD; Phone Number: 617-632-6844
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Not yet recruiting
      • Mayo Clinic (Data Collection Only)
      • Contact: Yucai Wang, MD; Phone Number: 507-284-2511
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Not yet recruiting
      • Washington University (Data Collection Only)
      • Contact: Dilan Patel, MD; Phone Number: 314-747-8173
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Cancer Center at Basking Ridge (Limited Protocol Activities)
      • Contact: Anita Kumar, MD; Phone Number: 646-608-3780
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
      • Contact: Anita Kumar, MD; Phone Number: 646-608-3780
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
      • Contact: Anita Kumar, MD; Phone Number: 646-608-3780
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities)
      • Contact: Anita Kumar, MD; Phone Number: 646-608-3780
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (Limited Protocol Activities)
      • Contact: Anita Kumar, MD; Phone Number: 646-608-3780
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center (All Protocol Activities)
      • Contact: Anita Kumar, MD; Phone Number: 646-608-3780
    • Rockville Centre, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (All Protocol Activities)
      • Contact: Anita Kumar, MD; Phone Number: 646-608-3780

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years at the time of signing Informed Consent
• ECOG 0-2
• Histologic diagnosis confirmed as relapsed/refractory mantle cell lymphoma according to WHO guidelines.
• Evidence of CD20 expression on neoplastic cells according to institutional pathology department guidelines
• Previously treated with at least one prior line of systemic therapy for mantle cell lymphoma. Prior BTKi failure is required. BTKi failure is defined as progression of disease during BTKi therapy or patients must have progressed or relapsed after completing BTK inhibitor therapy, or failed to achieve a PR following 12 weeks of BTK inhibitor therapy.
• Presence of evaluable disease

• Adequate bone marrow and organ function:

  • Absolute neutrophil count (ANC) ≥1,000 cells/mcL, unless felt to be secondary to underlying MCL (minimum ANC 500 cells/mcL)
  • Hgb ≥ 8 g/dL, unless felt to be secondary to underlying MCL (minimum Hgb 7.0 g/dL)
  • Platelet count ≥50,000 cells/mcL, unless felt to be secondary to underlying MCL (minimum platelet count 25,000 cells/mcL)
  • Renal function assessed by calculated Cockcroft-Gault creatinine clearance (CrCl; see Appendix A) ≥ 50 ml/min. See lenalidomide Treatment Plan, (Table 10-1), for lenalidomide dose adjustment for CrCl ≥ 30 mL/min and < 60 mL/min
  • Adequate hepatic function as determined by:
• Total bilirubin ≤1.5X upper limit of normal (ULN) unless secondary to Gilbert's syndrome or documented liver involvement by lymphoma. Patients with Gilbert's syndrome or documented liver involvement by lymphoma may be included if their total bilirubin is ≤ 5 x ULN
• Aspartate aminotransferase (AST, SGOT) and alanine aminotransferase (ALT, SGPT) ≤ 3 x ULN or ≤ 5 x ULN in cases of documented liver involvement.
• Willingness to receive adequate prophylaxis and/or therapy for thromboembolic events, unless contraindicated in the opinion of the investigator.
• Willingness to undergo confirmatory procedures for assessment of disease status and experimental studies as required by protocol, including bone marrow (BM) aspiration/biopsy and gastrointestinal endoscopy/colonoscopy with biopsy, and/or biopsy of other tissue when appropriate and medically feasible.
• Each patient must sign an informed consent form indicating that he or she understands the purpose of and procedures required for the study and are willing to participate.Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be eligible.
• Willingness of patients who can become pregnant, according to Revlimid/lenalidomide Risk Evaluation and Mitigation Strategy (REMS) criteria, to undergo pregnancy testing in accordance with REMS requirements
• Willingness of all patients to complete surveys and adhere to contraception requirements mandated by the Revlimid/lenalidomide REMS
• For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of <1% per year, for at least 28 days prior to Day 1 of Cycle 1, during the treatment period (including periods of treatment interruption), and for at least 2 months after the final dose of glofitamab, 28 days after the last dose of lenalidomide, 18 months after the last dose of obinutuzumab.
• For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm, as defined below: With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 2 months after the final dose of glofitamab, 28 days after last dose of lenalidomide, 6 months after the last dose of obinutuzumab. Men must refrain from donating sperm during this same period.
• Life expectancy ≥ 12 weeks as determined by patient's primary clinician

Exclusion Criteria:

• Investigational agent or anticancer therapy within 5 half-lives prior to start of study therapy except therapeutic monoclonal antibody treatment must be discontinued a minimum of 4 weeks prior to study therapy. An exception is BTKi therapy, which can be continued to prevent disease flare up until 1 day prior to start of study therapy.
• Major surgery within 4 weeks prior to planned start of study therapy.
• Radiotherapy within 7 days of the start of study therapy.
• CART infusion within 30 days prior to Day 1 of Cycle 1

• Active hepatitis B or C, as defined below:

  • HBV surface antigen positive
  • HBV surface antigen negative, HBV core antibody positive and detectable HBV viral DNA. Note: subjects who are HBV core antibody positive and viral DNA negative are eligible.
  • HCV antibody positive and HCV RNA positive.

• History of human immunodeficiency virus (HIV) unless all of the following criteria are met:

  • CD4+ T cell count ≥ 250 cells/mcL
  • No acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within 1 year prior to signing Informed Consent Form
  • Stable (no change in regimen for ≥ 4 weeks) and effective antiretroviral regimen, and HIV viral load < 400 copies/mL within 4 weeks prior to signing Informed Consent form
• Active concurrent malignancy requiring active therapy within the last 3 years with the exception of basal cell carcinoma limited to the skin, squamous cell carcinoma limited to the skin, carcinoma in situ of the cervix or breast, adequately treated lentigo maligna melanoma, or localized prostate cancer. Adjuvant or maintenance therapy to reduce the risk of recurrence of other malignancy previously treated for curative intent is permitted.
• Pregnant or lactating, intending to become pregnant, or unable/unwilling to comply with pregnancy testing and birth control measures and REMS enrollment, as described in inclusion criteria.
• 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 cycle 1, day 1.
• Clinically significant history of liver disease, including active viral or other hepatitis or current uncontrolled alcohol use disorder that would compromise patient's ability to safely participate in the trial, per clinician's judgment
• Active central nervous system (CNS) involvement with lymphoma, either parenchymal or leptomeningeal
• Presence of ≥Grade 2 toxicity (CTCAE v5.0) due to prior cancer therapy
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
• Patient with history of confirmed progressive multifocal leukoencephalopathy (PML)
• History of hypersensitivity to compounds of similar biological or chemical composition to IMiDs® and/or the excipients contained in the study drug formulations
• Previous treatment with bispecific antibody therapy directed against CD20 and CD3
• Previous treatment with lenalidomide or other IMiDs® within 12 months of treatment initiation on this study.
• Documented refractoriness to lenalidomide, defined as no response (PR or CR) within 6 months of therapy
• Autologous stem cell transplantation (ASCT) within the period ≤3 months prior to the signing of the informed consent form. Patients with a more distant history of ASCT must exhibit full hematologic recovery before enrollment into the study
• Allogenic stem cell transplantation within the period of ≤3 months prior to signing of the Informed Consent form, evidence of graft-versus-host-disease (GVHD), or receiving active immunosuppression for GVHD.
• A history of deep venous thrombosis/embolism, threatening thromboembolism or known thrombophilia or are at a high risk for a thromboembolic event in the opinion of the investigator and who are not willing/able to take venous thromboembolic event prophylaxis during the entire treatment period
• Concurrently use other anticancer or experimental treatments
• Administration of a live vaccine within 28 days prior to the start of study treatment (Cycle 1 Day 1).
• Prior treatment with systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents), within 2 weeks or five half-lives (whichever is shorter) prior to first dose of study treatment

• Corticosteroid therapy within 2 weeks prior to first dose of study treatment, with the following exceptions:

  • Short course systemic corticosteroids (total daily dose equivalent of prednisone 100mg or dexamethasone 20 mg) is permissible for disease control, improvement of performance status, or non-cancer indication if administered for ≤ 5 days, and must be discontinued prior to study initiation of study treatment. When clinically indicatedfeasible, tumor assessments such as imaging and biopsies should be performed prior to steroid administration, though this is not required for enrollment.
  • Chronic corticosteroid use of ≤20 mg prednisone equivalent per day, on a stable dose for ≥4 weeks prior to registration.
• Any life-threatening illness, medical condition, or organ system dysfunction that, in the opinion of the investigator, could compromise the subject's safety, or affect compliance with the protocol or interpretation of results.
• Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV or Objective Assessment Class C or D cardiac disease, myocardial infarction ≤ 6 months from registration, symptomatic congestive heart failure, unstable arrhythmia, or unstable angina) or significant pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants with Mantle Cell Lymphoma; Participants will be diagnosed with relapsed, refractory (R/R) mantle cell lymphoma (MCL) with prior BTK inhibitor (BTKi) failure	Drug: Glofitamab; IV Glofitamab; Drug: Obinutuzumab; IV Obinutuzumab; Drug: Lenalidomide; Oral Lenalidomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants who successfully receive glofitamab	Treatment feasibility defined as the proportion of participants who successfully receive glofitamab during cycles 1-3 without any dose delays of glofitamab for greater than 7 days	1 year

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Anita Kumar, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2024
• Primary Completion (Estimated): January 8, 2028
• Study Completion (Estimated): January 8, 2028

Study Registration Dates

• First Submitted: December 21, 2023
• First Submitted That Met QC Criteria: December 21, 2023
• First Posted (Actual): January 5, 2024

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Memorial Sloan Kettering Cancer Center; MCL; Mantle Cell Lymphoma; 23-319
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide; Obinutuzumab
• Other Study ID Numbers: 23-319

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No