Phase II Study of Pirtobrutinib With Venetoclax In Relapsed-Refractory MCL (Mantle Cell Lymphoma) Patients

NCT05529069 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2021-1108NCI-2022-07498
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if the combination of pirtobrutinib (also called LOXO-305) and venetoclax can help to control mantle cell lymphoma (MCL) that is relapsed (has come back) or refractory (has not responded to therapy).

Conditions

Mantle Cell Lymphoma; Non Hodgkin Lymphoma; Hematologic Malignancy

Outcome Measures

Primary Outcomes (1)

• ORR (overall response rate)

  through study completion an average of 1 year.

Study Arms (1)

Pirtobrutinib (LOXO-305) and Venetoclax (combination)

EXPERIMENTAL

Participants will have study visits every week during Cycle 1, and then on Day 1 of every cycle for the first year. After that, they will have study visits on Day 1 of every 2 cycles.

Drug: Pirtobrutinib; Drug: Venetoclax

Interventions

Pirtobrutinib DRUG

Given by PO

Also known as: LOXO-305

Pirtobrutinib (LOXO-305) and Venetoclax (combination)

Venetoclax DRUG

Given by PO

Also known as: ABT-199,

Pirtobrutinib (LOXO-305) 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:

• Confirmed diagnosis of mantle cell lymphoma in tissue biopsy by hematopathology with/without chromosome translocation t(11;14), (q13;q32) and/or overexpress cyclin D1 in tissue biopsy. Cyclin D1 negative MCL (confirmed by hematopathology at MDACC are allowed).
• The patient is able to take oral medications
• Relapsed MCL (irrespective of prognostic factors) including any lines or prior therapy or patients who had prior ibrutinib, acalabrutinib, zanubrutinib, other BTK inhibitor or anti CD19-CART therapy, single agent or in combination (without prior venetoclax) or relapsed high risk MCL including any or all of the following (Blastoid/pleomorphic histology), High Ki-67 (≥50%), TP53 mutated or del17p by FISH, NSD2, NOTCH2, CDKN2A mutated or MYC positive by FISH or MYC, Bcl2 amplification, complex karyotype or high risk biologic MIPI score
• Willing and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
• Age from \>=18 years at the time of signing the informed consent.
• Patients may have at least 1 site of radiographically assessable disease (i.e., lymph node longest diameter \[LDi\] \>= 1.5 cm, not necessary for disease assessable by positron emission tomography \[PET\]/computerized tomography \[CT\], extra nodal site \>= 1.0 cm in LDi. Patients with BM only or GI only relapse are allowed.
• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less.
• Disease free of prior malignancies with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or other malignancies in remission (including prostate cancer patients in remission from radiation therapy, surgery or brachytherapy), not actively being treated, with a life expectancy \> 3 years pertaining to prior malignancy. PI could use judgment in the best interest of patients.
• Patients must have relapsed or refractory MCL (irrespective of prior BTK inhibitor or anti CD19 CART exposure).
• Prothrombin time (or international normalized ratio) and partial thromboplastin time not to exceed 1.2 times the institutional upper limit of normal range (patients with an elevated prothrombin time and known lupus anticoagulant may be eligible for participation after consulting the IND sponsor).
• Adequate BM function independent of growth factor or PRBC or platelet transfusion support (within 14 days of Screening assessment and criteria must be met on C1D1 without transfusion/G-CSF within 7 days of assessment, per local laboratory reference range at screening as follows:
• platelet count \>=50, 000/mm3;
• absolute neutrophil count (ANC) \>= 1000/mm3 unless cytopenia is clearly due to marrow involvement from MCL
• total hemoglobin \>= 8 g/dL (without transfusion support within 2 weeks of screening); If any of the above-mentioned cytopenias (a-c) are present due to significant BM involvement, at least 30% BM involvement by MCL (requiring transfusion or granulocyte colony-stimulating factor \[G-CSF\] support) MCL patients may proceed with enrollment after discussion with the PI or Co-PI. Cytopenias may not be due to evidence of myelodysplastic syndrome (MDS) or hypoplastic BM.
• Adequate organ function as defined by the following laboratory values:

You may not qualify if:

• Known central nervous system (CNS) involvement by lymphoma. Patients with previous treatment for CNS involvement who are neurologically stable and without evidence of disease (as shown by MRI brain and/or CSF or clinical exam by neurologists may be eligible if a compelling clinical rationale is provided to institutional IND sponsor contact.)
• History of bleeding diathesis
• History of stroke or intracranial hemorrhage within 6 months of C1D1
• Vaccination with live vaccine within 28 days prior to enrollment.
• Have a known hypersensitivity to any of the excipients of Pirtobrutinib or to the intended covalent BTK inhibitor if randomized to control arm.
• Patients who experienced a major bleeding event or grade ≥ 3 arrhythmia on prior treatment with a BTK inhibitor. NOTE: Major bleeding is defined as bleeding having one or more of the following features: potentially life-threatening bleeding with signs or symptoms of hemodynamic compromise; bleeding associated with a decrease in the hemoglobin level of at least 2g per deciliter; or bleeding in a critical area or organ (e.g., retroperitoneal, intraarticular, pericardial, epidural, or intracranial bleeding or intramuscular bleeding with compartment syndrome).
• Pregnant or lactating females.
• Known and uncontrolled HIV infection. Participants with HIV (known HIV 1/2 antibodies positive) are allowed if all of the following conditions are met:
• CD4+ T-cell counts ≥350 cells/μL;
• Participants with a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections may be eligible, if they have not had an opportunistic infection within the past 12 months;
• If participant is on antiretroviral, evaluation of the specific agents must be performed in order to determine if participant is eligible (e.g., excluding patients taking strong CYP3A inhibitors such as ritonavir). If necessary, evaluate the feasibility of switching to an alternate effective ARV therapy (ART) regimen before study participation. Participants need to be on established ART for at least 4 weeks and have an HIV viral load less than 400 copies/mL prior to enrollment.
• Screening for HIV infection is not required
• Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on criteria below: 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 hepatitis B polymerase chain reaction (PCR) evaluation before enrollment. Patients who are hepatitis B PCR positive will be excluded. 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 enrollment. Patients who are hepatitis C RNA positive will be excluded.
• Evidence of other clinically significant uncontrolled condition(s) including but not limited to, uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the investigator and IND sponsor may pose a risk for patient participation. Screening for chronic conditions is not required.
• Pregnancy, lactation or plan to breastfeed during the study or within 6 months of the last dose of study treatment

Sponsors & Collaborators

• Loxo Oncology: collaborator
• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Lymphoma, Non-Hodgkin; Hematologic Neoplasms

Interventions

pirtobrutinib; venetoclax

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site; Hematologic Diseases

Study Officials

• Preetesh Jain, MD, DM, PhD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Preetesh Jain, MD, DM, PhD

CONTACT

(713) 563-8786; pjain@mdanderson.org

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: September 1, 2022
• First Posted: September 6, 2022
• Study Start: January 25, 2023
• Primary Completion (Estimated): April 28, 2027
• Study Completion (Estimated): April 28, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (1)