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

NCT ID: NCT04446962

Last Updated: 2025-09-25

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-30
• Study Completion Date: 2035-08-30

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).

Detailed Description

The objective of this proposal is to test the feasibility and efficacy of two targeted induction chemotherapies obtained by adding either Lenalidomide or Ibrutinib to a standard Rituximab-High Dose (HD) Methotrexate (MTX) based induction chemotherapy regimen. The R-MPV regimen is chosen as the backbone chemotherapy because of its wide use with robust reproducible results and a good and manageable toxicity profile

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: R-MPV with Lenalidomide

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

Group Type: ACTIVE_COMPARATOR

Lenalidomide

Intervention Type: 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.

Arm B: R-MPV with Ibrutinib

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

Group Type: ACTIVE_COMPARATOR

Ibrutinib

Intervention Type: 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.

Interventions

Lenalidomide

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.

Intervention Type: DRUG

Ibrutinib

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.

Intervention Type: DRUG

Other Intervention Names

Revlimid; Imbruvica

Eligibility Criteria

Inclusion Criteria

1. Newly diagnosed Primary Central Nervous System Lymphoma (PCNSL).

2. a) Aged between 18 and 60 (>18 and < 60) - phase IB b) Aged between 18 and 65 (≥ 18 and ≤ 65) - phase II.

3. 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.

4. Measurable lesion on MRI with gadolinium enhancement.

5. Adequate hematological, renal and hepatic function (Laboratory Parameters realized within 14 days before inclusion):

1. Absolute neutrophil count (ANC) >1000/mm3

2. Platelets > 100,000/mm3 independent of transfusion support

3. Alanine aminotransferase and aspartate aminotransferase ≤ 3 x Upper Limit of Normal (ULN)

4. Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin

5. Estimated Glomerular Filtration Rate ≥ 60 mL/min/1.73m2.

6. Able to swallow capsules.

7. Karnofsky performance status: 40-100% for the phase IB and no restriction on the KPS for the phase II.

8. 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.

9. 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.

10. Women of childbearing potential (WCBP)* must have a negative serum (beta-human chorionic gonadotropin [B-hCG]) or urine pregnancy test at inclusion.

11. 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.

Exclusion Criteria

1. Histology other than DLBCL.

2. Positive HIV serology.

3. Active viral infection with Hepatitis B or C virus.

4. Preexisting immunodeficiency and/or organ transplant recipient.

5. Isolated Central Nervous System (CNS) relapse of systemic Non-Hodgkin's Lymphoma.

6. Prior treatment for PCNSL (except corticosteroids).

7. Isolated primary vitreo-retinal lymphoma.

8. Major surgery, within 4 weeks prior to the first dose of study drug. Stereotactic biopsy and vitrectomy are not considered major surgery.

9. History of stroke or intracranial hemorrhage (except minor post biopsy hemorrhage) within 6 months prior to inclusion.

10. Requires anticoagulation with warfarin or equivalent vitamin K antagonists.

11. Requires treatment with strong CYP3A4 inhibitors.

12. Pregnancy or lactation.

13. Clinically significant cardiovascular disease.

14. Any other active malignancy, except basocellular carcinoma and non-invasive cervix cancer.

15. Inclusion in another experimental anti-cancer drug therapy.

16. No social security affiliation.

17. Persons under legal protection.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute, France

OTHER_GOV

Sponsor Role: collaborator

Institut Curie

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven LE GOUILL, PhD

Role: STUDY_DIRECTOR

Institut Curie

Locations

CHU Amiens

Amiens, , France

CHU Angers

Angers, , France

CH côte Basque

Bayonne, , France

CHU Besançon

Besançon, , France

Institut Bergonié

Bordeaux, , France

CHU Caen

Caen, , France

CHU Clermont-Ferrand

Clermont-Ferrand, , France

CH Colmar

Colmar, , France

CHU Créteil

Créteil, , France

CHU Dijon

Dijon, , France

CHU Grenoble

Grenoble, , France

CHRU Lille

Lille, , France

CHU Limoges

Limoges, , France

CHU Lyon

Lyon, , France

CHU La Timone Marseille

Marseille, , France

CHU Nancy

Nancy, , France

CHU Nantes

Nantes, , France

Centre Lacassagne

Nice, , France

CHU Nîmes - Carémeau

Nîmes, , France

Institut Curie

Paris, , France

Hôpital Cochin

Paris, , France

CHU Pitié-Salpêtrière

Paris, , France

CHU Poitiers

Poitiers, , France

CHU Rennes

Rennes, , France

Centre Henri Becquerel

Rouen, , France

CHU Strasbourg-Hôpital Hautepierre

Strasbourg, , France

IUCT -Oncopole

Toulouse, , France

CHU Tours

Tours, , France

Countries

France

References

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.

Reference Type: RESULT

PMID: 39300447 (View on PubMed)

Other Identifiers

2019-003632-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IC 2019-02

Identifier Type: -

Identifier Source: org_study_id