Phase II Study of Pirtobrutinib, Rituximab (PR) in Previously Untreated Low and Intermediate Risk MCL (Mantle Cell Lymphoma) Patients

NCT06263491 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2023-0413NCI-2024-01325
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if the chemotherapy-free combination of pirtobrutinib (also called LOXO-305) and rituximab can help provide long term remission in low and intermediate risk MCL.

Conditions

Mantle Cell Lymphoma

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 (2)

Cohort A

EXPERIMENTAL

If participants show that they have no MRD, participants will be in Cohort A and will stop taking pirtobrutinib. Participants will continue to be observed and tested for MRD, and participants will be able to continue receiving the drug if you test positive.

Drug: Rituximab; Drug: Pirtobrutinib

Cohort B

EXPERIMENTAL

If participants test positive for MRD at the 24 month time point, participants will be in Cohort B and the participant will continue taking pirtobrutinib.

Drug: Rituximab; Drug: Pirtobrutinib

Interventions

Rituximab DRUG

Given by PO

Also known as: Rituxan

Cohort A; Cohort B

Pirtobrutinib DRUG

Given by PO

Cohort A; Cohort B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The study will enroll 50 previously untreated low and medium risk MCL patients. Estimated 3 patients per month at minimum for enrollment.
• Age ≥ 18 years old
• Pathology confirmed diagnosis of mantle cell lymphoma. CD20 positivity is needed. Cyclin D1 negative MCL are allowed after confirming the diagnosis of MCL from hem-path at MDACC.
• Newly diagnosed MCL with no prior therapy for MCL (age \>= 18 years)
• Participants with preexisting well-controlled cardio-vascular comorbidities - participants on anticoagulants (excluding warfarin and vitamin K antagonists), antiplatelet, anti-hypertensive, prior ablation, anti-arrhythmia, prior arrhythmias, baseline EKG abnormalities and cardiology clearance are allowed. Ejection fraction \>=50% and cardiology evaluation may be needed. (Echo and EKG and cardiology consultation within 2 months prior to C1D1 are allowed).
• Understand and voluntarily sign an IRB-approved informed consent form.
• Participants 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. But participants with isolated gastrointestinal, bone marrow or spleen only disease patients are allowed.
• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less (See Appendix III).
• Prothrombin time (or international normalized ratio) and partial thromboplastin time not to exceed 1.2 times the institutional upper limit of normal range (participants with an elevated prothrombin time and known lupus anticoagulant may be eligible for participation after consulting the study PI).
• A. 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:
• a. platelet count \>=75,000/mm3; b. absolute neutrophil count (ANC) \>= 1000/mm3 unless cytopenia is clearly due to marrow involvement from MCL c. 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.
• B. Adequate organ function as defined by the following laboratory values:
• a. Creatinine clearance. \>=30 mL/min (by Cockcroft-Gault method, APPENDIX I), b. Total bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN with documented liver involvement and/or Gilbert's Disease or controlled immune hemolysis or considered an effect of regular blood transfusions.
• c. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<3 x ULN, or \< 5 x upper limit of normal if hepatic metastases are present.
• \. Projected life expectancy of \>12 weeks pertaining to lymphoma. 11. Female participants must be surgically sterile, postmenopausal (for at least 1 year), or have confirmed negative results for a pregnancy test at screening, on a serum sample obtained within 7 days prior to initiation of study treatment.

You may not qualify if:

• Participants with central nervous system involvement with mantle cell lymphoma or with suspected or confirmed progressive multifocal leukoencephalopathy (PML) are excluded since those participants have very poor prognosis, need aggressive intensive chemoimmunotherapy and intrathecal chemotherapy along with BTK inhibitors and these participants would not be eligible for this study.
• High risk MCL - any or all of the following (Blastoid/pleomorphic histology), High Ki-67 (\>50%), Bulky disease (nodes \>5 cm, spleen \>20 cm), lymphocytosis \>=50,000 cells/uL, TP53 mutated or del17p by FISH. Presence of MYC rearrangement positive by FISH or MYC, Bcl2 amplification, complex karyotype or high-risk biologic MIPI (with Ki-67%)
• Major surgery within 4 weeks prior to registration
• History of bleeding diathesis
• Known active CMV. Unknown or negative status are eligible
• 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 medical monitor may pose a risk for participant participation. Screening for chronic conditions is not required
• Clinically significant cardiovascular diseases as determined after cardiology consultation, including uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within 6 months of screening or any Class 3 (moderate) or 4 (severe) cardiac disease following the New York Heart Association Classification. Otherwise, significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, bradycardia, or QTc \>470 msec.
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
• Pregnancy or plan to become pregnant during the study or within 1-month post pirtobrutinib or 12 months post Rituxan. (Note: post rituxan, WOCBP should not become pregnant for 12 months post last dose of rituxan).
• Lactation during the study or for 1 week after last dose of pirtobrutinib (Note that the USPI for rituxan recommends no lactation during treatment and for 6 months after last dose)
• Current treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and/or strong P-gp inhibitors. Because of their effect on CYP3A4, use of any of the following within 3 days of study therapy start or planned use during study participation is prohibited - grapefruit or grapefruit products, Seville oranges or products from Seville oranges, star fruit
• Participants taking warfarin and/or equivalent vitamin K antagonists
• Has difficulty with or is unable to swallow oral medication or has significant gastrointestinal disease that would limit absorption of oral medication.
• History of stroke or intracranial hemorrhage within 6 months of C1D1
• Vaccination with live vaccine within 28 days prior to enrollment.

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

Conditions

Lymphoma, Mantle-Cell

Interventions

Rituximab; pirtobrutinib

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

• Ranjit Nair, MBBS, MD, DM, PhD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ranjit Nair, MD

CONTACT

713-745-8041; rnair@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: February 9, 2024
• First Posted: February 16, 2024
• Study Start: May 29, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

US (1)