Clinical Trial to Evaluate the Efficacy and Safety of Pirtobrutinib With Rituximab in Patients With Mantle Cell Lymphoma

NCT07285590 | Recruiting Phase 2

• 2 other identifiers: IMCL-20232024-511983-97-00
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 16

Brief Summary

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.

Conditions

Mantle Cell Lymphoma (MCL)

Keywords

lymphoma; Geltamo; Rituximab; Pirtobrutinib; Mantle cell lymphoma; MCL

Outcome Measures

Primary Outcomes (1)

• 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.

  At the end of Cycle 6 (each cycle is 28 days)

Secondary Outcomes (12)

• To evaluate the activity of Pirtobrutinib-Rituximab combination along time in terms of ORR

  At month 6, month 12 and month 24.

• Evaluation of MRD

  After cycle 6, cycle 12, cycle 30, cycle 36, cycle 42, cycle 48 (each cycle is 28 days), and End of treatment (28 days after las administration of Study drug).

• To determine the safety and tolerability of P-R combination

  Baseline, during all the cycles day 1 visit (each cycle is 28 days) and at EoT (28 days afert las administration of Study drug).

• To assess the patient Health-related Quality of Life (HRQoL)

  Between baseline and month 6, month 12, and month 24 and End of Study (month 48)

• To assess the patient Health-related Quality of Life (HRQoL).

  Between baseline and month 6, month 12, and month 24 and End of Study (month 48)

Study Arms (1)

Pirtobrutinib with rituximab

EXPERIMENTAL

Patients will receive a P-R combination for at least 24 cycles (C24). The first cycle of P-R will be administered at day 1 (baseline) . Pirtobrutinib discontinuation will be decided after C24, according to the MRD response and the TP53 mutational status. Rituximab treatment will end up at C23.

Drug: Pirtobrutinib and rituximab

Interventions

Pirtobrutinib and rituximab DRUG

Patients 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.

Pirtobrutinib with rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Asymptomatic patients
• Eastern Cooperative Oncology Group (ECOG) performance status \<2 (0-1)
• Clinical stage I-IV according to the Ann Arbor classification with no symptoms attributable to MCL
• Patients with a leukemic non-nodal presentation with mainly bone marrow or peripheral blood involvement are eligible. Other asymptomatic clinical presentations are acceptable in case of low tumour burden, including MCL with lymph node enlargement ≤ 3 cm in the largest diameter and with low proliferation index (Ki67 \< 30%)
• The following laboratory values at screening:
• Neutrophil count ≥ 1×109/L, Haemoglobin level ≥ 100 g/L and platelet count ≥100×109/L
• Transaminases (AST and ALT) ≤ 3 x ULN
• Total bilirubin ≤1.5 x ULN unless bilirubin rise is due to Gilbert's disease
• Calculated creatinine clearance ≥ 30 ml/min according to Cockcroft/Gault Formula (140 - age) × body weight (kg) × 0.85 (if female)/ serum creatinine (mg/dL) × 72
• Adequate coagulation, defined as activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) and prothrombin (PT) or (international normalized ratio (INR) not greater than 1.5 x ULN.
• Stable disease without evidence of clinical progression for at least 3 months. Patients in prolonged observation may be included (over 3 months).

You may not qualify if:

• 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).
• Organ dysfunction related to MCL including creatinine level \> 2 mg/dl or altered liver biochemistry (\> 3x ULN).
• Serum LDH over ULN
• Known central nervous system (CNS) infiltration.
• Expected MCL therapy requirement in a short time (\< 3 months)
• Anticoagulation requirement with vitamin K antagonists
• History of bleeding diathesis
• Prolongation of the QT interval corrected for heart rate (QTcF) \> 470 msec. QTcF is calculated using Fridericia's Formula (QTcF): QTcF = QT/(RR0.33). Correction of suspected drug-induced QTcF prolongation can be attempted at the investigator's discretion and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation. Correction for underlying bundle branch block (BBB) allowed.
• NOTE: Patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker
• Patients who have tested positive for Human Immunodeficiency Virus (HIV) are excluded due to risk of opportunistic infections with both HIV and BTK inhibitors. For patients with unknown HIV status, HIV testing will be performed at Screening and result must be negative for enrolment.
• Known active cytomegalovirus (CMV) infection. Unknown or negative status are eligible.
• Concomitant or previous malignancies the last 2 years other than basal skin cancer or in situ uterine cervix cancer.

Sponsors & Collaborators

• Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea: lead
• Evidenze Health España (CRO): collaborator
• Eli Lilly and Company: collaborator

Study Sites (16)

Instituto Português de Oncologia de Lisboa Francisco Gentil

Lisbon, Lisbon District, 1099-023, Portugal

RECRUITING

Unidade Local De Saude De Santa Maria E.P.E.

Lisbon, Lisbon District, 1649-028, Portugal

NOT YET RECRUITING

INSTITUT CATALÀ D'ONCOLOGIA (ICO). Hospital Germans Trias I Pujol.

Badalona, Barcelona, 08916, Spain

NOT YET RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona, 08035, Spain

RECRUITING

Hospital Clinic de Barcelona

Barcelona, Barcelona, 08036, Spain

RECRUITING

Institut Català d'oncologia de L'Hospitalet (ICO-L'Hospitalet)

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

NOT YET RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, Madrid, 28007, Spain

RECRUITING

Clínica Universidad Navarra

Madrid, Madrid, 28027, Spain

RECRUITING

Hospital Ramon y Cajal

Madrid, Madrid, 28034, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Madrid, 28041, Spain

RECRUITING

Hospital Clínico Universitario Virgen de la Arrixaca

El Palmar, Murcia, 30120, Spain

RECRUITING

Hospital Costa del Sol

Marbella, Málaga, 29603, Spain

RECRUITING

Clínica Universidad Navarra

Pamplona, Pamplona, 31008, Spain

RECRUITING

Hospital Universitario de Salamanca

Salamanca, Salamanca, 37007, Spain

RECRUITING

Hospital Clínico de Valencia

Valencia, Valencia, 46010, Spain

RECRUITING

Hospital Universitario y Politécnico La Fe

Valencia, Valencia, 46026, Spain

NOT YET RECRUITING

Related Links

• Geltamo Web page

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Lymphoma

Interventions

pirtobrutinib; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Eva Giné Soca

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Auxi Moreno

CONTACT

+34 683 636 850; amoreno@geltamo.com

Ana María Méndez

CONTACT

+34 942 203 450; administracion@geltamo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2025
• First Posted: December 16, 2025
• Study Start: September 30, 2025
• Primary Completion (Estimated): December 1, 2032
• Study Completion (Estimated): December 1, 2032
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Information will be available beginning 6 months after final publication with no end date established
• Access Criteria: Access to trial IPD can be requested by qualified researchers and will be provided following review and approval of a research and execution of a Data Sharing Agreement (DSA).

Locations

PT (2); ES (14)