Acalabrutinib and Rituximab in Elderly Patients With Untreated Mantle Cell Lymphoma
Status:
Recruiting
Trial end date:
2027-01-01
Target enrollment:
Participant gender:
Summary
This is a phase II trial, with the aim of developing a chemotherapy-free regimen for
untreated patients with mantle cell lymphoma (MCL).
Acalabrutinib (ACP-196) is a next generation bruton tyrosine kinase (BTK) inhibitor, more
selective than ibrutinib, and without in vitro antagonism of anti-CD20 directed
immunotherapies, indicating that its combination with rituximab may be more active than the
combination of ibrutinib and rituximab.
In this trial proposal, we will also assess the activity of this combination in comparison to
a historical control of ibrutinib + rituximab, consisting of the experimental arm of
ibrutinib + rituximab in the randomized ENRICH trial (EudraCT number 2015-000832-13), and
data from our previous trial with R-bendamustine-lenalidomide (NLG-MCL4).
The duration of treatment will be a minimum of 12 months. Patients in molecular remission in
blood and bone marrow and in complete remission according to CT, will then stop
acalabrutinib, but continue on rituximab for a maximum of 36 months. Patients that are
minimal residual disease positive (MRD+) will be evaluated again every 6 months and continue
on acalabrutinib for a maximum of 36 months.
Patients without a molecular marker, that cannot be followed with MRD, will stop treatment if
in CR with PET at 12 months, and be followed by PET-CT every 6 months for a maximum of 36
months.
Patients who convert back to MRD positive after stopping acalabrutinib are reinstalled on
acalabrutinib until progression.
Patients with TP53 aberrations and/or blastoid histology, will monitor MRD but continue with
treatment until progression regardless of MRD results.
A planned interim analysis will be performed when 40 patients have undergone response
assessment after 6 months, for futility and efficacy.
If less than 16 of 40 patients obtain a CR, the trial will be stopped due to futility.