Phase 2 Open Label Randomized Study of Pirtobrutinib and Brexucabtagene Autoleucel in R/R MCL

NCT06553872 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: MCC-22557J2N-US-I010
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

This is a phase 2, open-label, randomized, multicenter clinical trial in patients with relapsed/refractory mantle cell lymphoma (R/R MCL) who meet the criteria for standard-of-care FDA label for CD19 CAR T-cell therapy with brexucabtagene autoleucel (brexu-cel).

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Progression-free survival (PFS) - Historical comparison

  The one-sample log-rank test will be used to determine if there's a statistically significant difference in PFS in patients treated on this trial of pirto plus brexucel compared to a historical control.

  12 months

• Progression-free survival (PFS) - Comparison between arm A and arm B

  The one-sample log-rank test will be used to determine if there's a statistically significant difference in PFS in patients treated with concurrent pirtobrutinib ("con-pirto") versus patients treated with no concurrent pirtobrutinib ("con-none").

  12 months

Secondary Outcomes (4)

• Severe ICANS

  Up to 60 days post CAR T

• Severe CRS

  Up to 60 days post CAR T

• Overall Response Rate (ORR)

  Up to 48 months

• Overall survival (OS)

  Up to 48 months

Study Arms (2)

Arm A

EXPERIMENTAL

Participants will recieve pirtobrutinib as bridging therapy from day -27 to day -7. Participants randomized to Arm A (n=30) will continue to receive concurrent pirtobrutinib ("con-pirto"), starting at day -6 and continued until 1-year post-CD19 CAR T-cell therapy with brexucel.

Drug: Pirtobrutinib; Drug: Brexucabtagene Autoleucel

Arm B

EXPERIMENTAL

Participants will recieve pirtobrutinib as bridging therapy from day -27 to day -7. Participants on Arm B (n=30) will discontinue pirtobrutinib after day -7 and will not receive concurrent pirtobrutinib ("con-none") between day -6 and 1-year post-CD19 CAR T-cell therapy.

Drug: Pirtobrutinib; Drug: Brexucabtagene Autoleucel

Interventions

Pirtobrutinib DRUG

Pirtobrutinib is a non-covalent BTKi that has preserved activity in the presence of mutations that drive BTKi resistance.

Also known as: Jaypirca

Arm A; Arm B

Brexucabtagene Autoleucel DRUG

Brexucabtagene autoleucel is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy (brexu-cel).

Also known as: Tecartus

Arm A; Arm B

Eligibility Criteria

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

You may qualify if:

• Patients with a histologically confirmed diagnosis of mantle cell lymphoma (MCL) will be eligible.
• Adult males or females who are 18 years of age or older at time of signing informed consent.
• Must have ability to comprehend and the willingness to sign written informed consent for study participation.
• Eligible to receive CAR T-cell therapy (Brexucabtagene autoleucel) for MCL by the standard of care label, which states: "TECARTUS or Brexucabtagene autoleucel is a CD19-directed genetically modified autologous T-cell immunotherapy indicated for the treatment of: Adult patients with relapsed or refractory mantle cell lymphoma (MCL)"
• ECOG performance status 0 to 2.
• Patients are required to have the following washout periods prior to leukapheresis. In addition, prior treatment-related AEs must have recovered to Grade ≤ 1 with the exception of alopecia and Grade 2 peripheral neuropathy.
• Targeted agents (i.e. BTK inhibitors), investigational agents, therapeutic monoclonal antibodies or cytotoxic chemotherapy: 5 half-lives or 2 weeks, whichever is shorter
• Antibody-drug conjugates (ADC): 10 weeks
• Radiation therapy: Broad field radiation (≥ 30% of the bone marrow or whole brain radiotherapy): 14 days. Palliative limited field radiation: 7 days. Note: In the case of known central nervous system (CNS) involvement by systemic lymphoma: Patients with previous treatment for CNS involvement who are neurologically stable and without evidence of disease may be eligible if a compelling clinical rationale is provided by the Investigator and with documented Sponsor approval.
• Bendamustine or other purine analogues: 3 months.
• Corticosteroids: 5 days
• The effects of Pirtobrutinib on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial 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 as outlined in criteria below:
• Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through safety follow up and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants in their understanding confirmed.
• Willingness of women of reproductive potential and their partners to observe highly effective birth control methods for the duration of treatment and for 1 month following the last dose of study treatment (see Section 4.3 and Section 4.4 for further details)
• Women of childbearing potential must have a negative serum pregnancy test at screening and before the first dose of pirtobrutinib and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed.

You may not qualify if:

• Patients who have previously received treatment with pirtobrutinib for \>2 months prior to study enrollment are ineligible. Patients who are relapsed or refractory and then received less than 2 months of pirtobrutinib as "holding therapy" while awaiting CAR T-cell therapy evaluation, and who did not demonstrate disease progression while on pirtobrutinib holding therapy, are eligible.
• Patients who have previously discontinued pirtobrutinib due to disease progression, intolerance, or toxicity.
• Patients who are currently receiving or who have received any investigational study agent ≤4 weeks prior to screening visit are ineligible.
• Prior treatment with chimeric antigen receptor (CAR) T-cell therapy.
• Participants with clinically significant or uncontrolled cardiac disease, including unstable angina or acute coronary syndrome within the past 2 months prior to randomization, history of myocardial infarction within 3 months prior to randomization, documented LVEF by any method of ≤ 40% in the 12 months prior to randomization, or ≥ Grade 3 NYHA functional classification system of heart failure.
• Uncontrolled or symptomatic arrhythmias, including prolongation of the QT interval corrected for heart rate (QTcF) \> 470 msec. QTcF is calculated using Fridericia's Formula (QTcF): QTcF = QT/(RR0.33). Correction of suspected drug induced QTcF prolongation can be attempted at the investigator's discretion and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation. Correction for underlying bundle branch block (BBB) allowed. Note: Patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker
• Evidence of active uncontrolled/untreated infection (viral, bacterial, fungal, opportunistic) of any origin.
• Participants with active immunologic or inflammatory/autoimmune disease affecting the CNS, and unrelated to their disease under study or previous treatment.
• Patients with active CNS involvement of Mantle Cell Lymphoma. A history of CNS Mantle Cell Lymphoma is allowed, as long as it has cleared, and the patient is able to comply with study procedures. Patients with previous treatment for CNS involvement who are neurologically stable and without evidence of disease may be eligible with documented Sponsor approval.
• Known positive Human immunodeficiency virus (HIV) status. For patients with unknown HIV status, HIV testing will be performed at Screening and result must be negative for enrollment.
• Hepatitis B virus (HBV): Patients with positive hepatitis B surface antigen (HBsAg) are excluded. Patients with positive hepatitis B core antibody (anti-HBc) and negative HBsAg require a negative hepatitis B polymerase chain reaction (PCR) evaluation before randomization. Patients who are HBV DNA PCR positive will be excluded. Patients who are HBV DNA PCR negative with positive anti-HBc require prophylaxis against Hepatitis B reactivation (see Section 6.4 "General Guidance for Hepatic Monitoring").
• Hepatitis C virus (HCV): positive hepatitis C antibody. If positive hepatitis C antibody result, patient will need to have a negative result for hepatitis C ribonucleic acid (RNA) before randomization. Patients who are hepatitis C RNA positive will be excluded.
• Known active cytomegalovirus (CMV) infection. Unknown or negative status are eligible.
• Participants who require the concurrent use of chronic systemic steroids or immunosuppressant medications. Steroids should not be given within 5 days prior to leukapheresis. Concomitant bridging steroids (section 6.6) are allowed after leukapheresis.
• Known hypersensitivity or severe reaction to pirtobrutinib, similar compounds, or excipients.

Sponsors & Collaborators

• Bankhead-Coley Florida Biomedical Research Program: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: lead
• Eli Lilly and Company: collaborator

Study Sites (3)

Stanford Cancer Center

Stanford, California, 94305, United States

NOT YET RECRUITING

Univ of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

pirtobrutinib; brexucabtagene autoleucel

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

Study Officials

• Michael Jain, MD, PhD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ruthie Chae

CONTACT

813-745-3425; ICETtrials@moffitt.org

Study Design

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

Study Record Dates

• First Submitted: August 12, 2024
• First Posted: August 14, 2024
• Study Start: August 23, 2024
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

US (3)