GATE1: A Multicenter Phase II Study of Pirtobrutinib, Rituximab and Venetoclax Combination Therapy for Patients With Previously Untreated Mantle Cell Lymphoma

NCT06522386 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2024-0220NCI-2024-06175
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

Primary Objectives: To estimate the percent of participants who achieve a best response of complete response by the end of the PRV combination therapy in the induction therapy phase in patients with previously untreated MCL.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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 (1)

Pirtobrutinib, Rituximab and Venetoclax combination

EXPERIMENTAL

Drug: Pirtobrutinib; Drug: Rituximab; Drug: Venetoclax

Interventions

Pirtobrutinib DRUG

Given by mouth

Pirtobrutinib, Rituximab and Venetoclax combination

Rituximab DRUG

Given by vein (IV)

Also known as: Rituxan

Pirtobrutinib, Rituximab and Venetoclax combination

Venetoclax DRUG

Given by mouth

Also known as: ABT-199, GDC-0199

Pirtobrutinib, Rituximab and Venetoclax combination

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old.
• Confirmed pathology diagnosis of MCL with t(11;14)(q13;q32) translocation and/or cyclin D1 overexpression (e.g., positive immunohistochemistry staining).
• MCL cells are CD20 positive (e.g., positive staining on immunohistochemistry or flow cytometry).
• No prior MCL-directed systemic treatment (such as chemotherapy, immunotherapy, targeted therapy, and cellular therapy) or radiotherapy.
• NOTE: A short course of corticosteroids (e.g., ≤ 1 week of intravenous or ≤ 2 weeks of oral) given for acute MCL-related symptoms or impending severe organ dysfunction is allowed, but a washout period of 3 days is required before registration.
• Have a clinical indication to treat (e.g., B symptoms, or symptomatic or progressive lymphadenopathy or hepatosplenomegaly, or cytopenia caused by MCL, etc.).
• ECOG performance status (PS) 0-2 (Appendix I).
• Evaluable disease, i.e., ANY of the following:
• Measurable lymph node or extranodal lesion with at least one dimeson \> 1.5 cm
• Spleen size \> 15 cm if spleen is involved by MCL (based on imaging or biopsy)
• WBC \> 15,000/µL if peripheral blood is involved by MCL (based on flow cytometry)
• Bone marrow involvement by MCL (\> 10% of cellularity)
• Endoscopically visible lesion that is biopsy-proven to be involved by MCL
• Meet ALL following criteria in lab values obtained ≤ 14 days prior to registration:
• Absolute neutrophil count (ANC) ≥ 1000/µL without growth factor support

You may not qualify if:

• CNS involvement by MCL (e.g., any parenchymal, leptomeningeal, CSF, cranial nerve, or spinal cord or nerve root involvement).
• Pregnant or plan to become pregnant during study treatment or within 1 month following the last dose of pirtobrutinib and/or venetoclax or within 12 months following the last dose of rituximab; or breast-feeding or plan to breastfeed during study treatment or within 1 week following the last dose of pirtobrutinib and/or venetoclax or within 6 months following the last dose of rituximab.
• Malabsorption syndrome or other condition that precludes enteral route of administration.
• Any of the following medication requirement or recent use:
• Use of a strong or moderate cytochrome P450 (CYP) 3A inhibitor or inducer ≤ 7 days prior to registration
• Anticipated requirement of a strong CYP3A inhibitor or inducer during the study that cannot be substituted
• Use of grapefruit or grapefruit products, Seville oranges or products from Seville oranges, or star fruit ≤ 3 days prior to registration, or planned use during the study
• Anticipated requirement of a strong P-gp inhibitor during the study
• Anticoagulation with a vitamin K antagonist ≤ 7 days prior to registration or anticipated use during the study
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• History of a bleeding disorder (e.g., hemophilia, von Willebrand disease, etc.) or active bleeding.
• Active or recent infections, including but not limited to:
• Active infections requiring treatment (such as systemic antibiotics, antivirals, or antifungals) ≤ 7 days prior to registration
• History of a positive COVID-19 (SARS-CoV-2) test (nucleic acid or antigen) within 4 weeks prior to registration, or presence of continued COVID-19-related clinically relevant symptoms or COVID-19-related significant pulmonary infiltrates in patients with a history of COVID-19 disease
• Human Immunodeficiency Virus (HIV) positive NOTE: Patients who have tested positive for Human Immunodeficiency Virus (HIV) are excluded due to potential drug-drug interactions between anti-retroviral medications and pirtobrutinib and risk of opportunistic infections with both HIV and irreversible BTK inhibitors. For patients with unknown HIV status, HIV testing will be performed at Screening and result should be negative for the patient to be eligible.

Sponsors & Collaborators

• AbbVie: collaborator
• M.D. Anderson Cancer Center: lead
• Eli Lilly and Company: collaborator
• Genentech, Inc.: collaborator

Study Sites (2)

Mayo Clinic in Rochester

Rochester, Minnesota, 55902, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

pirtobrutinib; Rituximab; 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)

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

Study Officials

• Michael Wang, MD, MS

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 22, 2024
• First Posted: July 26, 2024
• Study Start: January 30, 2025
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2029
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

US (2)