NCT04783415

Acalabrutinib, Umbralisib, and Ublituximab for the Treatment of Previously Untreated Mantle Cell Lymphoma

A Phase II Study of BTK Inhibitor Acalabrutinib and PI3Kδ Inhibitor Umbralisib in Combination With Ublituximab (AU2) in Patients With Previously Untreated Mantle Cell Lymphoma (MCL)

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies the effects of acalabrutinib, umbralisib, and ublituximab in treating previously untreated mantle cell lymphoma. Acalabrutinib and umbralisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Ublituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving acalabrutinib and umbralisib with ublituximab may work better in treating mantle cell lymphoma.

Detailed description

PRIMARY OBJECTIVE: I. Evaluate the anti-tumor activity of acalabrutinib, umbralisib and ublituximab (AU2) regimen as induction therapy in patients with treatment-naïve mantle cell lymphoma (MCL), as assessed by the complete response (CR) rate. SECONDARY OBJECTIVES: I. Evaluate the overall response rate (ORR) to AU2 in treatment-naive MCL. II. Evaluate the progression-free survival (PFS), overall survival (OS) and duration of response (DOR) in patients with treatment-naïve MCL who received AU2. III. Evaluate the safety and tolerability of AU2 in patients with treatment-naive MCL. EXPLORATORY OBJECTIVES: I. Examine the T-cell populations and functionality in patients treated with AU2. II. Explore the predictive value of minimal residual disease (MRD) in MCL. III. Explore the mechanisms of resistance to AU2 therapy. OUTLINE: INDUCTION: Patients receive ublituximab intravenously (IV) over 90 minutes-4 hours on days 1, 8, and 15 of cycle 1 and days 1 of cycles 2-6. Patients also receive acalabrutinib orally (PO) twice daily (BID) and umbralisib PO once daily (QD) on days 1-28. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive ublituximab IV on day 1 on cycles 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30. Patients also receive acalabrutinib Po BID and umbralisib PO QD on day 1-28. Treatment repeats every 28 days for 24 cycles in the absence of disease progression of unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days and then every 6 months for 2 years.

Conditions

• Mantle Cell Lymphoma

Interventions

Type	Name	Description
DRUG	Acalabrutinib	Given PO
BIOLOGICAL	Ublituximab	Given IV
DRUG	Umbralisib	Given PO

Timeline

• Start date: 2021-03-26
• Primary completion: 2022-07-31
• Completion: 2025-09-20
• First posted: 2021-03-05
• Last updated: 2024-12-02
• Results posted: 2023-11-18

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study