NCT04836832

Acalabrutinib and Duvelisib for the Treatment of Relapsed/Refractory Indolent Non-Hodgkin Lymphoma

A Phase Ib/II Study of Duvelisib and Acalabrutinib in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (DUAL Trial)

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Narendranath Epperla · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib/II trial studies the side effects of acalabrutinib and duvelisib and how well they work in treating patients with indolent non-Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Acalabrutinib inhibits a signaling molecule called Bruton tyrosine kinase and blocks cancer cell proliferation, growth, and survival. Duvelisib is designed to block a protein called PI3 kinase in order to stop cancer growth and cause changes in the immune system that may allow the immune system to better act against cancer cells. Giving acalabrutinib and duvelisib together may work better to block cancer growth than therapy of either drug alone.

Detailed description

PRIMARY OBJECTIVES: I. To assess the safety and tolerability of the combination of acalabrutinib and duvelisib in patients with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL). II. Determine maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). III. To estimate the overall response rate (ORR, Lugano 2014, computed tomography \[CT\] based) of acalabrutinib in combination with duvelisib at 6 months in follicular lymphoma (FL) and marginal zone lymphoma (MZL) cohorts. SECONDARY OBJECTIVES: I. To evaluate the activity of acalabrutinib and duvelisib as measured by ORR based on positron emission tomography (PET) scan at 6 months, duration of response (DOR) and 2-year progression-free survival (PFS). II. To capture patient-reported outcomes (PROs). EXPLORATORY OBJECTIVE: I. To determine the correlation of the clinical activity of acalabrutinib in combination with duvelisib with established biomarkers and identify putative novel markers. OUTLINE: This is a phase Ib, dose-escalation study of duvelisib, followed by a phase II study. Patients receive acalabrutinib orally (PO) twice daily (BID), and duvelisib PO BID on days 1-28. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 19, patients receive acalabrutinib PO BID for up to 60 months in absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, and then every 3 months thereafter.

Conditions

• Recurrent Follicular Lymphoma
• Recurrent Marginal Zone Lymphoma
• Recurrent Nodal Marginal Zone Lymphoma
• Recurrent Splenic Marginal Zone Lymphoma
• Refractory Follicular Lymphoma
• Refractory Indolent Non-Hodgkin Lymphoma
• Refractory Marginal Zone Lymphoma
• Refractory Nodal Marginal Zone Lymphoma
• Refractory Splenic Marginal Zone Lymphoma

Interventions

Type	Name	Description
DRUG	Acalabrutinib	Given PO
DRUG	Duvelisib	Given PO

Timeline

• Start date: 2022-07-01
• Primary completion: 2023-12-31
• Completion: 2024-12-31
• First posted: 2021-04-08
• Last updated: 2022-06-07

Regulatory

• FDA-regulated drug study