NCT04939272

Copanlisib and Venetoclax for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma

A Phase 1/2 Study of Copanlisib and Venetoclax in Patients With Relapsed or Refractory Mantle Cell Lymphoma

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects, best dose, and effectiveness of copanlisib and venetoclax in treating patients with mantle cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Copanlisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving copanlisib and venetoclax may help treat patients with mantle cell lymphoma.

Detailed description

PRIMARY OBJECTIVES: I. To assess the safety, tolerability, and the maximum tolerated dose (MTD) of copanlisib hydrochloride (copanlisib) and venetoclax in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). (Phase 1) II. To estimate the efficacy (as measured by overall rate of response \[ORR\]) of copanlisib in combination with venetoclax in patients with R/R MCL. (Phase 2) SECONDARY OBJECTIVES: I. To characterize the safety profile of copanlisib in combination with venetoclax in patients with R/R MCL. (Phase 2) II. To evaluate duration of response (DOR) and progression-free survival (PFS) associated with combined administration of copanlisib/venetoclax. (Phase 2) III. To evaluate an overall survival (OS) associated with combined administration of copanlisib/venetoclax. (Phase 2) IV. To characterize the pharmacokinetics (PK) profile of copanlisib and venetoclax. (Phase 2) EXPLORATORY OBJECTIVES: I. Evaluate the emergence of resistant clones, as determined by the presence of novel mutations and expression of BCL2 family proteins. II. Characterize the T-cell population balance in patients treated with copanlisib/venetoclax. OUTLINE: This is a phase I, dose-escalation study of copanlisib hydrochloride, followed by a phase II study. Patients receive copanlisib hydrochloride intravenously (IV) over 1 hour on days 1, 8, and 15, and venetoclax orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years.

Conditions

• Recurrent Mantle Cell Lymphoma
• Refractory Mantle Cell Lymphoma

Interventions

Type	Name	Description
DRUG	Copanlisib Hydrochloride	Patients receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 for each cycle. Copanlisib will be given at 30mg, 45mg, or 60 mg depending on the assigned dose level.
DRUG	Venetoclax	Patients receive venetoclax PO QD on days 1-28 for each cycle. Venetoclax will have a weekly dose ramp up in cycle one from 20mg, 50mg, 100mg, 200mg, and then 400mg daily thereafter starting from cycle 2.

Timeline

• Start date: 2022-06-29
• Primary completion: 2026-02-24
• Completion: 2026-02-24
• First posted: 2021-06-25
• Last updated: 2025-05-01

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study