A Study of Acalabrutinib Plus Venetoclax and Rituximab in Participants With Treatment Naïve Mantle Cell Lymphoma — TrAVeRse  

Mantle Cell Lymphoma (MCL) Clinical Trial

Official title: A Multicentre, Phase II, Randomised, Open-label Study to Evaluate the Efficacy of Acalabrutinib in Combination With Venetoclax and Rituximab in Participants With Treatment Naïve Mantle Cell Lymphoma (TrAVeRse)

Status Recruiting

Clinical Trial Summary

TrAVeRse is a multicentre, open-label, randomised, Phase II study of AVR in treatment naïve MCL participants. The primary objective will be to assess the rate of MRD-negative CR at end of induction after completing 13 cycles of AVR. Participants achieving an MRD-negative CR at the end of AVR induction will be randomised to continued acalabrutinib or observation. Participants who progress during observation may receive retreatment with acalabrutinib

Clinical Trial Description

Most mantle cell lymphoma (MCL) patients require treatment at diagnosis. Currently, despite the availability of a number of chemo-immunotherapy-based frontline treatment options, there is no clear superior regimen or curative option for MCL patients. This study aims to evaluate the efficacy of a chemotherapy-free triplet combination regimen of a Bruton's Tyrosine Kinase-inhibitor (acalabrutinib), a BCL2 inhibitor (venetoclax) and an anti-CD20 monoclonal antibody (rituximab) (AVR), in treatment naïve MCL participants.

The study will also assess the feasibility of response-adapted treatment cessation for participants who achieve minimal residual disease (MRD) negative complete response (CR) after AVR induction and the efficacy of retreatment with acalabrutinib in a subgroup of participants who relapse after stopping all anti-lymphoma therapy.

All participants are planned to receive 13 cycles of AVR induction. Each cycle is 28 days. During the induction phase, acalabrutinib is administered twice a day (bd) orally for a total of 13 cycles starting on Cycle 1, venetoclax is administered once daily orally for a total of 12 cycles starting on Cycle 2, and rituximab is administered intravenously on Day 1 of every cycle, for a total of 12 cycles starting on Cycle 1.

• Participants who complete 13 cycles of AVR induction will be centrally tested for MRD status at completion of Cycle 13 and will continue to receive acalabrutinib bd for one full additional cycle (Cycle 14) while awaiting the results of the centralized MRD assessment and evaluation of disease response.

• Participants whose status is MRD-negative CR at the end-of-Cycle 13 assessments will be randomised in a 1:1 ratio to acalabrutinib or observation starting at Cycle 15. Those randomised to acalabrutinib will continue to receive acalabrutinib until progressive disease (PD), death, or unacceptable toxicity whereas those randomised to observation will not receive any anti-lymphoma treatment while in observation. Among the latter group, participants who relapse while in observation may be retreated with acalabrutinib at the time of relapse.

• Participants whose status is MRD-positive CR, PR, or stable disease at the end-of-Cycle 13 assessments will continue to receive acalabrutinib until PD, death, or unacceptable toxicity. The total duration of the study will be approximately 67 months.

Objectives and Endpoints

Primary:

•To assess the efficacy of AVR by assessment of MRD-negative CR rate at the end of AVR induction, i.e., following completion of Cycle 13

Secondary:

• To assess the efficacy of AVR by assessment of MRD-negative CR rate at any time during the study

• To assess the efficacy of AVR by assessment of overall response rate (ORR), CR rate, duration of response (DoR), time to next treatment (TTNT), progression-free survival (PFS), event-free survival (EFS), and overall survival (OS)

• To assess the efficacy of continued acalabrutinib treatment compared to observation, in participants achieving MRD-negative CR after AVR induction by assessment of post randomisation time to first occurrence of relapse or death, EFS, and TTNT

• To assess the safety and tolerability of AVR with continued acalabrutinib or observation until disease progression ;

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma (MCL)

• NCT number: NCT05951959
• Study type: Interventional
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center@astrazeneca.com
• Status: Recruiting
• Phase: Phase 2
• Start date: December 13, 2023
• Completion date: January 17, 2029