A Study to Evaluate Acalabrutinib, in Combination With the R-CHOP Standard of Care, for Previously Untreated Mantle Cell Lymphoma in Spain

Phase 2

Not yet recruiting

• Conditions: Mantle-cell Lymphoma
• Interventions: Drug: Acalabrutinib + R-CHOP standard of care; Drug: Acalabrutinib combination with Rituximab; Drug: Acalabrutinib monotherapy

• Registration Number: NCT07029737
• Lead Sponsor: AstraZeneca

Brief Summary

This is a single-arm, open-label, multicenter, non-indication seeking phase II trial to describe the efficacy and safety of patients with mantle cell lymphoma (MCL) receiving acalabrutinib in combination with R-CHOP for the front-line treatment of MCL in Spain.

Acalabrutinib will be administered until disease progression if medically appropriate, along with R-CHOP based on institutional standards. After 6 cycles of acalabrutinib in combination with R-CHOP, subjects who tolerate treatment and not progressing, will then receive monotherapy acalabrutinib. In addition, subjects who achieve a response (PR or greater) will receive maintenance rituximab every other 28-day cycle for a maximum of 12 additional doses. Thereafter, subjects receive monotherapy acalabrutinib until disease progression or treatment discontinuation.

Detailed Description

This is a single-arm, open-label, multicenter, non-indication seeking phase II trial to describe the efficacy and safety of patients with mantle cell lymphoma (MCL) receiving acalabrutinib in combination with the standard of care CIT in Spain, for the front-line treatment of MCL in Spain.

Approximately 55 subjects meeting the eligibility criteria for the study will receive acalabrutinib, in combination with R-CHOP for previously untreated MCL, in approximately 20 Spanish sites.

Acalabrutinib will be administered 100 mg twice per day (BID) orally (PO) until disease progression if medically appropriate, along with R-CHOP based on institutional standards.

A safety run-in will be performed for the first 6 patients older than 75 years included in the study (timeframe: after completing three cycles of the induction phase).

A confirmatory assessment of sufficient efficacy for the acalabrutinib + R-CHOP regimen will be performed for the first 10 patients treated with acalabrutinib + R-CHOP (timeframe: after completing six induction cycles).

After 6 cycles of acalabrutinib in combination with R-CHOP, subjects who tolerate treatment and not progressing, will then receive monotherapy acalabrutinib 100 mg BID. In addition, subjects who achieve a response (PR or greater) will receive maintenance rituximab 375 mg/m2 on Day 1 of every other 28-day cycle for a maximum of 12 additional doses. Thereafter, subjects will receive monotherapy acalabrutinib 100 mg BID (or last tolerated dose) until disease progression or treatment discontinuation for any reason.

The planned duration of recruitment is approximately 12 months. Data will be collected since the inclusion of the first subject, with a maximum prospective follow-up of 30 months since the last subject in. Each subject will be followed up from screening, until the withdrawal from the study, lost to follow-up, death or the end of the study (i.e., 30 months since the last patient in), whichever occurs first.

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-12
• Study First Submitted QC: 2025-06-12
• Last Update Submitted: 2025-06-12
• Study Start: 2025-06-15
• Study First Posted: 2025-06-19
• Last Update Posted: 2025-06-19
• Primary Completion: 2027-06-15
• Study Completion: 2028-12-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 55

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single Arm	Acalabrutinib + R-CHOP standard of care	Acalabrutinib + R-CHOP standard of care (Induction Phase) plus Acalabrutinib + Rituximab (Maintenance Phase) / Acalabrutinib Monotherapy (Maintenance Phase)
Single Arm	Acalabrutinib combination with Rituximab	Acalabrutinib + R-CHOP standard of care (Induction Phase) plus Acalabrutinib + Rituximab (Maintenance Phase) / Acalabrutinib Monotherapy (Maintenance Phase)
Single Arm	Acalabrutinib monotherapy	Acalabrutinib + R-CHOP standard of care (Induction Phase) plus Acalabrutinib + Rituximab (Maintenance Phase) / Acalabrutinib Monotherapy (Maintenance Phase)

Primary Outcome Measures

Name	Time	Method
Best Overall Response Rate (ORR)	From acalabrutinib start to approximately 1 year thereafter	Investigator-assessed best ORR (CR+PR) as per the Lugano Classification for NHL

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DoR)	From the time of the first documentation of response to disease progression or death; up to 30 months since the last subject in	DoR, defined as the time from the first documentation of investigator-assessed CR or PR to disease progression per the Lugano Classification for NHL or death from any cause in the absence of disease progression. Measure of interest: 30-month DoR.
Time To Response (TTR)	From acalabrutinib start to the first investigator assessed response; up to 30 months since the last subject in	TTR, defined as the time from the date of acalabrutinib start to the first investigator-assessed CR or PR per the Lugano Classification for NHL. Measure of interest: median TTR.
Progression-Free Survival (PFS)	From acalabrutinib start to disease progression or death; up to 30 months since the last subject in	PFS, defined as the time from the date of acalabrutinib start to investigator-assessed disease progression as per the Lugano Classification for NHL or death from any cause, whichever occurs first. Measure of interest: 30-month PFS.
Overall Survival (OS)	From acalabrutinib start to death; up to 30 months since the last subject in	OS, defined as the time from the date of acalabrutinib start to the date of death from any cause. Measure of interest: 30-month OS.
Safety and tolerability profile	From enrollment to 30 days after the last dose of acalabrutinib or post-acalabrutinib-treatment disease progression; up to 30 months since the last subject in	Number and percentage of patients with each MedDRA coded and CTCAE graded adverse (AEs) and serious adverse events (SAEs).; Incidence of AEs of clinical interest for acalabrutinib. Incidence of grade ≥3 AEs. Incidence of AEs leading to acalabrutinib dose modification, temporary interruption or permanent discontinuation.

Trial Locations

Locations (1)

Research Site; 🇪🇸 Valencia, Spain