Phase 2 Study of BTKi-Rituximab Induction Followed by Glofitamab Consolidation in High Risk Untreated MCL Patients - WINDOW-4 Study

NCT07257055 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2025-0423NCI-2025-08762
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

to learn if giving glofitamab after treatment with BTKi-rituximab can help to control high-risk MCL.

Conditions

Phase 2 Study; MCL; BTKi; Rituximab; Glofitamab

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (3)

1-Induction

EXPERIMENTAL

Phase 2 Induction Treatment with BTKi-R - Rituximab/Ruxience + Acalabrutinib/Zanubrutinib

Drug: Acalabrutinib; Drug: Rituximab

2-Consolidation

EXPERIMENTAL

Phase 2 Consolidation Treatment with Glofitamab

Drug: Glofitamab

3-Maintenance

EXPERIMENTAL

Phase 2 Maintenance Treatment with BTKi-R - Rituximab/Ruxience + Acalabrutinib/Zanubrutinib

Drug: Acalabrutinib; Drug: Rituximab

Interventions

Acalabrutinib DRUG

Given by po

Also known as: Zanubrutinib

1-Induction; 3-Maintenance

Rituximab DRUG

Given by IV

Also known as: Ruxience

1-Induction; 3-Maintenance

Glofitamab DRUG

Given by IV

2-Consolidation

Eligibility Criteria

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

You may not qualify if:

• Isolated bone marrow or GI only disease MCL participants and/or lack of any measurable disease, except if participants have leukemic phase MCL with any high risk features.
• Pregnant or breast-feeding females.
• Participants who are primary refractory to BTKi-R (No response/progressive disease within first 3 months of BTKi-R)
• Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug.
• Current life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the subject's safety or put the study at risk.
• Known HIV infection.
• Known history of hemophagocytic lymphohistiocytosis (HLH)
• Known or suspected chronic active Epstein-Barr virus infection (clearance with infectious disease is needed to allow these participants)
• Positive SARS-CoV-2 test within 7 days prior to enrollment. Rapid antigen test result is also acceptable.
• Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative polymerase chain reaction (PCR) and must be willing to undergo DNA PCR testing during the study to be eligible. Those who are HBsAg positive or hepatitis B PCR positive will be excluded (unless cleared by hepatology and ID team after discussion with study PI). Subjects who are hepatitis C antibody positive will need to have a negative PCR result to be eligible. Those who are hepatitis C PCR positive will be excluded.
• Prior malignancy (or any other malignancy requiring active treatment), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ ca prostate, in situ melanoma (\> 5 mm margins) or other cancer from which the subject has been disease free for ≥ 3 years or which will not limit survival to \< 3 years or not on active systemic chemotherapy.
• Central nervous system involvement with mantle cell lymphoma or with suspected or confirmed progressive multifocal leukoencephalopathy (PML). Magnetic resonance imaging (MRI) of the brain, if performed, showing evidence of central nervous system (CNS) lymphoma or Lumbar puncture with flow cytometry, if performed, with CSF involvement.
• History or presence of uncontrolled CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with CNS involvement.
• Active bleeding, history of bleeding diathesis (such as Hemophilia or Von-Willebrand disease), Any history of intracranial bleed or stroke within 6 months of first dose of study drug.
• Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Interventions

acalabrutinib; zanubrutinib; Rituximab; glofitamab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Preetesh Jain, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Preetesh Jain, MD

CONTACT

713-563-8786; pjain@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: December 2, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): November 24, 2028
• Study Completion (Estimated): November 24, 2030
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

US (1)