Nemtabrutinib With Rituximab for the Treatment of Patients With Mantle Cell Lymphoma

NCT06572618 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 23421NCI-2024-06740P30CA033572
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial tests how well nemtabrutinib works with rituximab for the treatment of patients with mantle cell lymphoma. Nemtabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers such as mantel cell lymphoma at abnormal levels. This may help keep cancer cells from growing and spreading. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving nemtabrutinib with rituximab may kill more cancer cells in patients with mantle cell lymphoma.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete response rate

  Defined as the proportion of response-evaluable participants that achieve a best response of complete response (CR) at any time on the study prior to any disease progression or start of other anti-lymphoma therapy. Will be estimated among response-evaluable participants along with the 95% exact binomial confidence interval.

  Up to 5.5 years

Secondary Outcomes (5)

• Overall response rate

  Up to 5.5 years

• Progression free survival

  From start of protocol treatment to disease relapse/progression, start of other anti-lymphoma therapy, or death due to any cause, whichever occurs earlier, up to 5.5 years

• Overall survival

  From start of protocol treatment to death due to any cause, up to 5.5 years

• Duration of response

  From the first achievement of PR or CR to time of progressive disease, start of non-protocol anti-lymphoma therapy, or death, whichever earlier, up to 5.5 years

• Incidence of adverse events

  Up to 5.5 years

Study Arms (1)

Treatment (nemtabrutinib and rituximab)

EXPERIMENTAL

INDUCTION: Patients receive nemtabrutinib PO QD on days 1-28 of each cycle and rituximab IV on days 1, 8, 15 and 22 of cycle 1 and on day 1 of subsequent cycles. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive nemtabrutinib PO QD on days 1-28 of each cycle and rituximab IV on day 1 of event numbered cycles. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients may optionally continue to receive nemtabrutinib PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy during screening and may undergo throughout the trial and PET-CT scan and blood sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Biopsy; Drug: Nemtabrutinib; Procedure: Positron Emission Tomography and Computed Tomography Scan; Biological: Rituximab

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (nemtabrutinib and rituximab)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (nemtabrutinib and rituximab)

Nemtabrutinib DRUG

Given PO

Also known as: ARQ 531, ARQ-531, ARQ531, Bruton's Tyrosine Kinase Inhibitor ARQ 531, BTK Inhibitor ARQ 531, MK-1026

Treatment (nemtabrutinib and rituximab)

Positron Emission Tomography and Computed Tomography Scan PROCEDURE

Undergo PET-CT scan

Also known as: PET-CT Scan, PET/CT SCAN, Positron Emission Tomography/Computed Tomography

Treatment (nemtabrutinib and rituximab)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, BI-695500, BI695500, Blitzima, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC 102, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, IDEC102, Ikgdar, Mabtas, MabThera, Monoclonal Antibody IDEC-C2B8, PF 05280586, PF-05280586, PF05280586, Riabni, Ritemvia, Rituxan, Rituximab ABBS, Rituximab ARRX, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, Rituximab PVVR, Rituximab-abbs, Rituximab-arrx, Rituximab-blit, Rituximab-pvvr, Rituximab-rite, Rituximab-rixa, Rituximab-rixi, Rixathon, Riximyo, RTXM 83, RTXM-83, RTXM83, Ruxience, Truxima

Treatment (nemtabrutinib and rituximab)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative.
• Assent, when appropriate, will be obtained per institutional guidelines
• Age: ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Diagnosis of MCL established by histologic assessment including one of the following:
• Immunohistochemistry of the biopsy
• Flow cytometry of the biopsy
• Requiring treatment for MCL, and for which no prior systemic anticancer therapies have been received
• Local radiotherapy not exceeding a total dose of 20 gray (Gy) at least 2 weeks prior the first dose of study therapy is allowed
• Laboratory, radiographic, physical exam findings and/or symptoms attributable to MCL.
• Asymptomatic patients with blastoid or pleomorphic variant can be enrolled
• Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (as defined by Lugano Classification for non hodgkin's lymphoma \[NHL\])
• Without bone marrow involvement: absolute neutrophil count (ANC) ≥ 1,000/mm\^3, with bone marrow involvement: ANC ≥ 500/mm\^3
• NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement
• Without bone marrow involvement: platelets ≥ 75,000/mm\^3 with bone marrow involvement: platelets ≥ 30,000/mm\^3

You may not qualify if:

• Chronic systemic corticosteroid use \> 20 mg/day of prednisone or equivalent. Patients who received corticosteroid treatment with ≤ 20 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to day 1 of cycle 1. Patients may have received a brief (≤ 14 days) course of systemic steroids (≤ 100 mg prednisone equivalent per day) prior to initiation of study therapy for control of lymphoma-related symptoms
• History of severe bleeding disorder defined as an ongoing congenital or acquired condition that leads to an increased likelihood of bleeding
• Unstable cardiac disease as defined by one of the following:
• Acute myocardial infarction (MI) within the past 6 months
• NYHA (New York Heart Association) heart failure class III-IV
• Unstable angina (angina symptoms at rest) or new-onset angina (begun within the last 3 months)
• Corrected QT (QTc) prolongation (defined as a Fridericia's corrected QT interval \[QTcF\] \> 450 msecs) or other significant electrocardiogram (ECG) abnormalities including second degree atrioventricular (AV) block type II, third degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
• Positive for hepatitis C virus (HCV) virus by polymerase chain raction (PCR) at screening. Testing only required if the hepatitis (hep) C antibody is positive
• AIDS-defining opportunistic infection in the past 12 months prior to screening
• Known allergy/sensitivity (≥ grade 3) to nemtabrutinib or any of the excipients; history of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents
• Clinically significant uncontrolled illness
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection (as evaluated by the investigator) within 4 weeks prior to the first study treatment
• Primary or secondary central nervous system (CNS) lymphoma at the time of recruitment or history of CNS lymphoma
• Other active malignancy. Exceptions include malignancy treated with curative intent and no known active disease present for ≥ 2 years prior to initiation of protocol therapy; adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease; adequately treated in situ carcinomas (e.g., cervical, esophageal, etc.) without evidence of disease; asymptomatic prostate cancer managed with "watch and wait" strategy
• POCBP: Pregnant or breastfeeding

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

Specimen Handling; Biopsy; ARQ531; Magnetic Resonance Spectroscopy; Rituximab; CT-P10

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)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Alexey V Danilov

  City of Hope Medical 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: August 23, 2024
• First Posted: August 27, 2024
• Study Start: January 22, 2025
• Primary Completion (Estimated): January 8, 2027
• Study Completion (Estimated): January 8, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

US (2)