A Phase II Study of Glofitamab for Relapsed/Refractory Mantle Cell Lymphoma in Patients Previously Treated With CD19-Directed CAR T-Cell Therapy

Plain English Summary

Testing the Anti-cancer Drug, Glofitamab, in Patients With Mantle Cell Lymphoma (A Type of Blood Cancer) Whose Disease Returned After CAR-T Cell Therapy is a Phase 2 clinical trial sponsored by National Cancer Institute (NCI) studying Recurrent Mantle Cell Lymphoma, Refractory Mantle Cell Lymphoma. This trial tests the safety and effectiveness of Glofitamab and Obinutuzumab in patients with mantle cell lymphoma who have relapsed or are refractory after CD19-directed CAR T-cell therapy. Participation involves IV infusions of Glofitamab and Obinutuzumab, blood draws, and PET/CT scans. Patients must have previously received CD19-directed CAR T-cell therapy and have measurable disease. Alternatives include other targeted therapies or supportive care. The trial aims to enroll 20 participants.

Official Summary

This phase II trial tests the safety and side effects of glofitamab and obinutuzumab and how well they work in treating patients with mantle cell lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory) after receiving CD19-directed chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy is a form of immunotherapy where the immune system cell, T-cell, is changed to attack cancer cells. Glofitamab is a bispecific antibody that can bind to two different antigens at the same time. Glofitamab binds to CD3, a protein found on T cells (a type of white blood cell), and CD20 a protein found on B cells (another type of white blood cell) and some lymphoma cells. This may help the immune system kill cancer cells. Obinutuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Giving glofitamab and obinutuzumab may be safe, tolerable, and/or effective in treating patients with relapsed or refractory mantle cell lymphoma after receiving CD19-directed CAR T-cell therapy.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible patients must have relapsed or refractory mantle cell lymphoma after CD19-directed CAR T-cell therapy. Patients must be at least 18 years old and have no active brain metastases or other malignancies. Health requirements include normal blood counts and liver function tests. Pregnant women and those with active infections are not eligible. This trial is studying Recurrent Mantle Cell Lymphoma, Refractory Mantle Cell Lymphoma, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures the effectiveness of the treatment in shrinking tumors and improving survival rates. The specific primary outcome measures are: Objective response rate (Up to 2 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a significant treatment gap for patients with mantle cell lymphoma who have failed CD19-directed CAR T-cell therapy. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Recurrent Mantle Cell Lymphoma, Refractory Mantle Cell Lymphoma, where improved treatment options are needed.

Investor Insight

The market for advanced lymphoma treatments is growing, with this trial potentially offering a new option for patients who have exhausted other therapies. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if you have any active infections or if you are pregnant. Be prepared for IV infusions, blood draws, and imaging scans. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 20 participants

Interventions

• PROCEDURE: Biospecimen Collection — Undergo blood sample collection
• PROCEDURE: Computed Tomography — Undergo PET/CT
• BIOLOGICAL: Glofitamab — Given IV
• BIOLOGICAL: Obinutuzumab — Given IV
• PROCEDURE: Positron Emission Tomography — Undergo PET/CT

Primary Outcomes

• Objective response rate (Up to 2 years)

Secondary Outcomes

• Complete response rate (Up to 2 years)
• Progression-free survival (PFS) (Up to 24 months)
• Overall survival (OS) (Up to 24 months)
• Incidence of grade 3-4 cytokine release syndrome (Up to 2 years)
• Incidence of grade 3-4 neurologic toxicity (Up to 2 years)

Full Eligibility Criteria

Inclusion Criteria:

* Patients must have histologically or cytologically confirmed diagnosis of mantle cell lymphoma that is relapsed (disease progression after the last treatment regimen) or refractory (failure to achieve a partial or complete response from the last treatment regimen)
* Patients must have been previously treated with an anti-CD19 CAR T-cell therapy and have failed or been intolerant to Bruton's tyrosine kinase (BTK) inhibition. Both commercial and investigational CAR-T products which target CD19 will be allowed, including dual-targeting products
* Patients must have at least one bi-dimensionally measurable (defined as at least 1.5 cm) nodal lesion or one bi-dimensionally measurable (at least 1 cm) extranodal lesion, as measured on CT scan
* Age ≥ 18 years. Because no dosing or adverse event (AE) data are currently available on the use of glofitamab and obinutuzumab in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
* Absolute neutrophil count ≥ 1,000/mcL
* Platelets ≥ 50,000/mcL
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) or ≤ 3 x institutional ULN if the patient has Gilbert syndrome
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN
* Creatinine ≤ 1.5 x institutional ULN OR glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2
* Patients with human immunodeficiency virus (HIV) infection are eligible if on effective anti-retroviral therapy with undetectable viral load within 6 months
* Patients with a history of hepatitis B virus (HBV) infection or positive total hepatitis B core antibody (HBcAb) are eligible if the hepatitis B surface antigen (HBsAg) is negative and HBV DNA viral load is undetectable by polymerase chain reaction (PCR) at the time of screening. Such patients must be managed with appropriate anti-viral therapy, if indicated, and must be willing to undergo HBV DNA testing on day 1 of each cycle and every 3 months for at least 12 months after the final cycle of study treatment
* Patients with a history of hepatitis C virus (HCV) infection or positive HCV antibody are eligible if HCV ribonucleic acid (RNA) viral load is undetectable by PCR
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression and patients are asymptomatic from CNS involvement
* Patients with new, progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that patients are asymptomatic and immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial, such as patients with prostate cancer or breast cancer receiving hormonal therapy
* The effects of glofitamab and obinutuzumab on the developing human fetus are unknown. For this reason and because glofitamab and obinutuzumab are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 2 months after completion of glofitamab and 6 months after completion of obinutuzumab administration. Women of childbearing potential must use effective contraceptive precautions 2 months after completion of glofitamab treatment and 18 months after the last dose of obinutuzumab treatment
* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

Exclusion Criteria:

* Patients who have not recovered from AEs due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
* Patients who are receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to glofitamab and obinutuzumab
* Pregnant women are excluded from this study because glofitamab and obinutuzumab are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the 

Trial Locations

• JHU Sidney Kimmel Comprehensive Cancer Center LAO, Baltimore, Maryland, United States

Frequently Asked Questions

Related Conditions

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma
• Multiple myeloma
• Hodgkin lymphoma
• Lymphoma
• Lymphoproliferative disorders
• Immunotherapy
• Cancer immunotherapy
• Blood cancers
• Lymphoma subtypes

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