Pacritinib in Combination With a BTK Inhibitor for the Treatment of Patients With Relapsed or Refractory Mantle Cell Lymphoma

NCT06675123 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 23184NCI-2024-08854P30CA033572
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety and side effects of pacritinib in combination with a Bruton's tyrosine kinase (BTK) inhibitor and how well it works in treating patients with mantle cell lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Pacritinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. BTK inhibitors block a protein called BTK which is present on B-cell (a type of white blood cell) cancers such as mantle cell lymphoma at abnormal levels. This may help keep tumor cells from growing and spreading. Giving pacritinib in combination with a BTK inhibitor may be safe, tolerable and/or effective in treating patients with relapsed or refractory mantle cell lymphoma.

Conditions

Recurrent Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events (AEs)

  Will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. AEs will be summarized by type, severity, and attribution.

  Up to 30 days after last dose of study drug

Secondary Outcomes (3)

• Overall response rate (ORR)

  Up 12 months

• Duration of response (DOR)

  From the first achievement of PMR or CMR to time of progressive disease or death, whichever is earlier, assessed up to 12 months

• Progression-free survival (PFS)

  From start of protocol treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier, assessed up to 12 months

Study Arms (1)

Treatment (pacritinib, BTK inhibitor)

EXPERIMENTAL

Patients receive pacritinib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also continue to receive BTK inhibitor per standard of care. Additionally, patients undergo blood sample collection, optional tissue biopsy, bone marrow biopsy and aspiration and PET/CT throughout the study.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: BTK Inhibitor; Procedure: Computed Tomography; Drug: Pacritinib; Procedure: Positron Emission Tomography

Interventions

Biopsy PROCEDURE

Undergo optional tissue biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (pacritinib, BTK inhibitor)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Treatment (pacritinib, BTK inhibitor)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow biopsy and aspiration

Treatment (pacritinib, BTK inhibitor)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy and aspiration

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

Treatment (pacritinib, BTK inhibitor)

BTK Inhibitor DRUG

Given BTK inhibitor

Also known as: Tyrosine-Protein Kinase BTK Protein

Treatment (pacritinib, BTK inhibitor)

Computed Tomography PROCEDURE

Undergo PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (pacritinib, BTK inhibitor)

Pacritinib DRUG

Given PO

Also known as: Oral JAK2 Inhibitor SB1518, SB 1518, SB-1518, SB1518

Treatment (pacritinib, BTK inhibitor)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (pacritinib, BTK inhibitor)

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
• Be willing to provide tissue from a fresh core or excisional biopsy (performed as standard of care) of a tumor lesion prior to starting study therapy or from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Histologically confirmed diagnosis of mantle cell lymphoma according to the World Health Organization (WHO) classification with a characteristic immunophenotypic profile with CD5+, CD20+, and with either cyclin D1 expression by immunohistochemistry (IHC), or positive by fluorescence in situ hybridization (FISH) or cytogenetics for the t(11,14) translocation, or both. Patients whose tumor is negative for cyclin D1 expression are allowed providing hemato-pathology confirmation of the diagnosis of MCL
• Relapsed or refractory disease after at least 1 prior line of systemic therapy
• Relapse must have been confirmed histologically with hematopathology review. Exceptions may be granted with study PI approval
• Patient must be receiving treatment with single agent ibrutinib or another covalent BTK inhibitor (e.g., acalabrutinib, zanubrutinib), and must have previously achieved complete response (CR) or partial response (PR) to the BTK inhibitor, and must show evidence of progressive MCL at the time of enrollment
• Radiographically measurable disease by Lugano criteria (e.g., one or more nodal sites of disease ≥ 1.5 cm and/or extranodal sites of disease ≥ 1.0 cm in longest dimension)
• If measurable bone marrow involvement or circulating disease has been confirmed in the absence of radiographically measurable disease, exceptions may be granted with study PI approval
• Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
• WITHOUT BONE MARROW INVOLVEMENT: Absolute neutrophil count (ANC) ≥ 1,000/mm\^3
• NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement
• WITH BONE MARROW INVOLVEMENT: ANC ≥ 500/mm\^3

You may not qualify if:

• Autologous hematopoietic stem cell transplant within 3 months of day 1 of protocol therapy
• Prior allogeneic stem cell transplant
• Prior treatment with pacritinib or a janus kinase 2 (JAK2) inhibitor
• Concomitant treatment with pirtobrutinib
• Strong CYP3A4 inducers/ inhibitors within 14 days prior to day 1 of protocol therapy
• Note: Shorter washout periods may be permitted with approval of the study PI, provided that the washout period is at least five half-lives of the drug prior to day 1 of protocol therapy
• Systemic treatment with medications that increase the risk of bleeding, including anticoagulants, antiplatelet agents (except for aspirin dosages of ≤ 100 mg per day), anti-vascular endothelial growth factor (anti-VEGF) agents, and daily use of cytochrome C oxidase subunit 1 (COX-1) inhibiting non-steroidal anti-inflammatory drugs (NSAIDs) within 14 days prior to day 1 of protocol therapy
• Systemic treatment with medications with arrhythmogenic potential within 14 days prior to day 1 of protocol therapy. Shorter washout periods may be permitted with approval of the study PI, provided that the washout period is at least five half-lives of the drug prior to day 1 of protocol therapy
• Systemic steroid therapy for any cause must be tapered down to ≤ 20 mg/day prednisone or equivalent. Exceptions are:
• Use of brief (≤ 7 days) course of high dose corticosteroids (100 mg/day prednisone or equivalent) prior to initiation of study therapy for control of lymphoma-related symptoms
• Inhaled or topical steroids
• Use of mineralocorticoids for management of orthostatic hypotension
• Use of physiologic doses of corticosteroids for management of adrenal insufficiency
• Significant recent bleeding history defined as National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 within 3 months prior to day 1 of protocol therapy, unless precipitated by an inciting event (e.g., surgery, trauma, or injury)
• Known bleeding disorders (e.g., von Willebrand's disease or hemophilia)

Sponsors & Collaborators

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

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

Biopsy; Specimen Handling; 11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene; Magnetic Resonance Spectroscopy

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)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Tycel J Phillips

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2024
• First Posted: November 5, 2024
• Study Start: February 1, 2026
• Primary Completion (Estimated): March 8, 2028
• Study Completion (Estimated): March 8, 2028
• Last Updated: December 5, 2025

Record last verified: 2025-12

Locations

US (1)