NCT04546620

Acalabrutinib in Combination With R-CHOP for Previously Untreated Diffuse Large B-cell Lymphoma (DLBCL)

A Randomised Phase II Evaluation of Molecular Guided Therapy for Diffuse Large B-Cell Lymphoma With Acalabrutinib

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 453 (estimated)
• Sponsor: University Hospital Southampton NHS Foundation Trust · Academic / Other
• Sex: All
• Age: 16 Years
• Healthy volunteers: Not accepted

Summary

This study evaluates the addition of Acalabrutinib to current standard therapy of Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone (R-CHOP) for patients with previously untreated CD20 positive Diffuse Large B-cell Lymphoma (DLBCL) requiring full course chemoimmunotherapy. All patients will receive one cycle of R-CHOP. Two thirds of patients (Arm B) will go on to receive a further 5 cycles (every 21 days) of R-CHOP with Acalabrutinib. Acalabrutinib will be taken orally twice daily continuously in 21 day cycles. One third of patients (Arm A) will continue with 5 cycles of R-CHOP. Patients will be followed up initially for 24 months and then for disease status and survival until 114 progression events have been observed.

Detailed description

Diffuse large B-cell lymphoma (DLBCL) is the most common of the non-Hodgkin's lymphomas. Whilst the majority of patients will respond well to conventional treatment (R-CHOP - rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone), a significant number of patients lymphoma will not respond to initial therapy or their disease will return after completion of therapy. In a number of B-cell diseases an enzyme called, Bruton tyrosine kinase (BTK) prevents death of tumour cells, including in DLBCL. Acalabrutinib is an orally active BTK-inhibitor and it is thought that stopping BTK being activated may help in treating B-cell diseases. It is hypothesised that the addition of Acalabrutinib to standard R-CHOP immunochemotherapy may improve outcomes of patients with DLBCL. REMoDL-A is a randomised, phase II, open label, multicentre study that will be open in up to 50 centres. Up to 553 patients (453 randomised) will be recruited. Following informed consent all patients will receive 1 cycle of conventional R-CHOP chemotherapy. At the same time the diagnostic pathology block will be sent for molecular profiling by the Haematological Malignancy Diagnostic Service (HMDS). The delivery of the first cycle of R-CHOP will allow a sufficient interval for real time determination of molecular phenotype. Patients whose biopsies yield sufficient tumour material for profiling will be randomised 2:1 in favour of the experimental arm (R-CHOP + acalabrutinib). The primary objective will be to establish if combining acalabrutinib with R-CHOP improves efficacy, compared to R-CHOP alone, for the treatment of previously untreated patients with DLBCL to a degree that justifies further development of this approach.

Conditions

• Diffuse Large B Cell Lymphoma

Interventions

Type	Name	Description
DRUG	R-CHOP	Arm A patients will receive R-CHOP alone.
DRUG	R-CHOP + acalabrutinib	Arm B patients will receive R-CHOP in combination with acalabrutinib.

Timeline

• Start date: 2021-10-19
• Primary completion: 2027-11-01
• Completion: 2028-05-01
• First posted: 2020-09-14
• Last updated: 2025-08-06

Locations

33 sites across 1 country: United Kingdom