LOC-R01 Study of Lenalidomide and Ibrutinib in Association With Rituximab-Methotrexate Procarbazine Vincristin (R-MPV)

NCT04446962 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: IC 2019-022019-003632-23
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 28

Brief Summary

This study is to improve the first-line induction chemotherapy, by combining either Ibrutinib, or Lenalidomide, to a conventional immuno- chemotherapy of R-MPV type (Rituximab-Methotrexate-Procarbazine-Vincristine). This is a randomized Phase II trial, preceded by a dose escalation phase Ib. The objective of the phase Ib is to rule out any limiting toxicity of the new treatment associations, and to determine the recommended dose of Lenalidomide and Ibrutinib to be used in the phase II. In the phase II study, patients will receive 4 cycles of R-MPV + Lenalidomide or 4 cycles of R-MPV + Ibrutinib. The therapeutic response will be evaluated after the 2nd and the 4th cycle. Patients in good therapeutic response will proceed to the consolidation phase with Autologous Stem Cell Transplantation (ASCT).

Conditions

Lymphoma, Large B-Cell, Diffuse; Central Nervous System Neoplasms, Primary

Keywords

Lymphoma; Nervous System; Primary

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity (DLT) during the first cycle of treatment for each treatment arm.

  Occurrence of a Dose Limiting Toxicity (DLT) during the first cycle of treatment for each treatment arm. The phase Ib is a 3+3 dose escalation design

  1 month

• Complete Response (CR) rate including unconfirmed Complete Response (uCR) at the end of the 4 cycles of induction therapy

  The primary endpoint for the phase II part of the study is the Complete Response (CR) rate including unconfirmed CR (CR+uCR) at the end of the 4 cycles of induction therapy. Assessment of response will be based on the International Primary Central Nervous System Lymphoma Collaborative Group (IPCG)

  4 months

Secondary Outcomes (7)

• Response rates (CR + uCR) after 2 cycles of induction treatment

  2 months

• Overall response (CR + uCR + Partial Response(PR)), stable disease (SD), and primary refractory patients (PD) after 2 cycles of induction treatment

  2 months

• Overall response (CR + uCR + Partial Response(PR)), stable disease (SD), and primary refractory patients (PD) after 4 cycles of induction treatment

  4 months

• Overall Survival (OS)

  142 months

• Progression-Free Survival (PFS)

  142 months

Study Arms (2)

Arm A: R-MPV with Lenalidomide

ACTIVE COMPARATOR

Lenalidomide in association with R-MPV as a targeted induction treatment

Drug: Lenalidomide

Arm B: R-MPV with Ibrutinib

ACTIVE COMPARATOR

Ibrutinib in association with R-MPV as a targeted induction treatment

Drug: Ibrutinib

Interventions

Lenalidomide DRUG

Patients will receive 4 cycles of induction chemotherapy with R-MPV + Lenalidomide using the Maximum Tolerated Dose (MTD) of Lenalidomide and Ibrutinib as determined in the phase-Ib part of the study.

Also known as: Revlimid

Arm A: R-MPV with Lenalidomide

Ibrutinib DRUG

Patients will receive 4 cycles of induction chemotherapy with R-MPV + Ibrutinib, using the Maximum Tolerated Dose (MTD) of Lenalidomide and Ibrutinib as determined in the phase-Ib part of the study.

Also known as: Imbruvica

Arm B: R-MPV with Ibrutinib

Eligibility Criteria

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

You may qualify if:

• Newly diagnosed Primary Central Nervous System Lymphoma (PCNSL).
• a) Aged between 18 and 60 (\>18 and \< 60) - phase IB b) Aged between 18 and 65 (≥ 18 and ≤ 65) - phase II.
• Histological confirmed diagnosis of Primary central nervous system lymphoma of Diffuse Large B-Cell Lymphomas (DLBCL) type OR patients with a measurable typical cerebral lesion on MRI with a diagnosis made by cytology and/or by flow cytometry on the vitreous or on the cerebral spinal fluid.
• Measurable lesion on MRI with gadolinium enhancement.
• Absolute neutrophil count (ANC) \>1000/mm3
• Platelets \> 100,000/mm3 independent of transfusion support
• Alanine aminotransferase and aspartate aminotransferase ≤ 3 x Upper Limit of Normal (ULN)
• Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
• Estimated Glomerular Filtration Rate ≥ 60 mL/min/1.73m2.
• Able to swallow capsules.
• Karnofsky performance status: 40-100% for the phase IB and no restriction on the KPS for the phase II.
• Able to understand teratogenic risks of the Lenalidomide and Ibrutinib. Patient must be able to understand and fulfill the Lenalidomide Pregnancy Prevention Plan requirements. This plan may be accepted by the person of confidence in case of impaired cognitive status of the patient.
• Women of childbearing potential (WCBP)\* and men who are sexually active must be practicing a highly effective method\*\* of birth control. Women should avoid a pregnancy while taking treatment by Lenalidomide or Ibrutinib and for up to 1 month after ending treatment. Men must agree to not to father a child or donate sperm during treatment by Lenalidomide or Ibrutinib and up to 3 months after the last dose of study drug.
• Signed informed consent, which could be signed by a person on confidence in case the neurologic status of the patient does not allow him to understand and/or to sign.

You may not qualify if:

• Histology other than DLBCL.
• Positive HIV serology.
• Active viral infection with Hepatitis B or C virus.
• Preexisting immunodeficiency and/or organ transplant recipient.
• Isolated Central Nervous System (CNS) relapse of systemic Non-Hodgkin's Lymphoma.
• Prior treatment for PCNSL (except corticosteroids).
• Isolated primary vitreo-retinal lymphoma.
• Major surgery, within 4 weeks prior to the first dose of study drug. Stereotactic biopsy and vitrectomy are not considered major surgery.
• Requires anticoagulation with warfarin or equivalent vitamin K antagonists.
• Requires treatment with strong CYP3A4 inhibitors.
• Pregnancy or lactation.
• Clinically significant cardiovascular disease.
• Any other active malignancy, except basocellular carcinoma and non-invasive cervix cancer.
• No social security affiliation.
• Persons under legal protection.

Sponsors & Collaborators

• Institut Curie: lead
• National Cancer Institute, France: collaborator

Study Sites (28)

CHU Amiens

Amiens, France

Location

CHU Angers

Angers, France

Location

CH côte Basque

Bayonne, 64100, France

Location

CHU Besançon

Besançon, France

Location

Institut Bergonié

Bordeaux, France

Location

CHU Caen

Caen, France

Location

CHU Clermont-Ferrand

Clermont-Ferrand, France

Location

CH Colmar

Colmar, France

Location

CHU Créteil

Créteil, France

Location

CHU Dijon

Dijon, France

Location

CHU Grenoble

Grenoble, France

Location

CHRU Lille

Lille, 69000, France

Location

CHU Limoges

Limoges, France

Location

CHU Lyon

Lyon, France

Location

CHU La Timone Marseille

Marseille, France

Location

CHU Nancy

Nancy, France

Location

CHU Nantes

Nantes, France

Location

Centre Lacassagne

Nice, France

Location

CHU Nîmes - Carémeau

Nîmes, 30029, France

Location

Institut Curie

Paris, 75005, France

Location

Hôpital Cochin

Paris, 75006, France

Location

CHU Pitié-Salpêtrière

Paris, 75013, France

Location

CHU Poitiers

Poitiers, France

Location

CHU Rennes

Rennes, 35000, France

Location

Centre Henri Becquerel

Rouen, 76000, France

Location

CHU Strasbourg-Hôpital Hautepierre

Strasbourg, 67098, France

Location

IUCT -Oncopole

Toulouse, France

Location

CHU Tours

Tours, France

Location

Related Publications (1)

• Alcantara M, Chevrier M, Jardin F, Schmitt A, Houillier C, Oberic L, Chinot O, Morschhauser F, Peyrade F, Houot R, Hoang-Xuan K, Ghesquieres H, Soussain C. Phase IB part of LOC-R01, a LOC network non-comparative randomized phase IB/II study testing R-MPV in combination with escalating doses of lenalidomide or ibrutinib for newly diagnosed primary central nervous system lymphoma (PCNSL) patients. J Hematol Oncol. 2024 Sep 19;17(1):86. doi: 10.1186/s13045-024-01606-w.

  PMID: 39300447 RESULT

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Central Nervous System Neoplasms; Lymphoma; Neurologic Manifestations

Interventions

Lenalidomide; ibrutinib

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Steven LE GOUILL, PhD

  Institut Curie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2020
• First Posted: June 25, 2020
• Study Start: October 30, 2020
• Primary Completion (Estimated): February 2, 2035
• Study Completion (Estimated): August 30, 2035
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.
• Access Criteria: Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).

Locations

FR (28)