This is a multicenter, international, open-label, single-arm phase II clinical trial designed to evaluate the activity and safety of a combination therapy with pirtobrutinib and rituximab (P-R) in treatment-naïve adult patients diagnosed with indolent clinical forms of Mantle Cell Lymphoma (MCL). The study applies a Simon's two-stage design, with an interim analysis after the first 16 patients to determine continuation based on complete remission rate (CRR) after 6 cycles.
Adult patients (≥18 years of age).
Written informed consent must be obtained before any study-specific assessment is performed.
Subjects with confirmed diagnosis of Mantle Cell Lymphoma according to the International Consensus Classification, (ICC) 2022] or World Health Organization (WHO) Classification 2022. Classical, small-cell variants and marginal-zone variants can be included.
Naïve patients for MCL management (no prior therapies, excluding diagnostic splenectomy)
Subjects with aggressive histological variants: blastoid and pleomorphic variants of MCL
B-cell monoclonal lymphocytosis with MCL phenotype
Presence of B symptoms or any relevant symptoms related to the MCL.
Nodal clinical forms with lymph node enlargement > 3 cm (largest diameter).
Single group
Pirtobrutinib and rituximab
DrugPatients will receive the study treatment (P-R combination) at day 1 (baseline) and during the treatment period (C24). Pirtobrutinib discontinuation per protocol will be decided after C24, according to the MRD response and the TP53 mutational status. Rituximab treatment will end up at C23.
Efficacy of Pirtobrutinib in combination with rituximab after 6 cycles
To assess the activity of Pirtobrutinib in combination with rituximab (P-R) as a therapeutic alternative to immunochemotherapy (R-Bendamustine or R-CHOP regimen) in patients with an indolent clinical presentation of MCL. The primary objective will be assessed by the complete remission rate (CRR), defined as the percentage of patients who achieve a complete response (CR) at the end of Cycle 6 of the P-R combination according to the Lugano Classification.
To evaluate the activity of Pirtobrutinib-Rituximab combination along time in terms of ORR
The activity of P-R combination will be assessed in the overall population according to the Lugano Classification in terms of: • overall response rate (ORR), defined as the percentage of patients who achieved partial response (PR) or complete response (CR) according to the Lugano Classification criteria.
Evaluation of MRD
To evaluate and compare the MRD detection ability of different MRD assays. The sensitivity, specificity, false positive and negative rates of MRD assays: Allele-specific oligonucleotide real-time quantitative Polymerase chain reaction (ASO-qPCR) and New Generation Sequencing (NGS) based assays.
To determine the safety and tolerability of P-R combination
The safety of P-R combination will be assessed by terms of Adverse Events (AEs), Severe Adverse Events (SAEs), Suspected Unexpected Adverse Reactions (SUSARs) during the P-R treatment, and second neoplasms and other serious events G≥3 occurring after treatment discontinuation. All AEs will be classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
To assess the patient Health-related Quality of Life (HRQoL)
This objective will be evaluated descriptively. The changes in the total score in patient HRQoL measured by patient reported outcomes (PRO): The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORT-QLQ-C30): This questionnaire is a self-administered tool specifically developed to assess the quality of life in treated cancer patients participating in international clinical trials. It is composed of both multi-item scales and single-item measures. It consists of 30 items grouped into three multi-items measures: i) functional scales (items 1-7, 20-27), ii) symptom scales (items 8-19, 28), and (3) global health status (items 29 and 30). Items from 1 to 27 are ranked from 1 (not at all) to 4 (very much). Items 29 and 30 are ranked from 1 (very poor) to 7 (excellent). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
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Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Lead sponsor
Evidenze CRO
Collaborator
Eli Lilly and Company
Collaborator
