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

Sponsor
Institut Curie (Other)
Overall Status
Recruiting
CT.gov ID
NCT04446962
Collaborator
National Cancer Institute, France (Other)
128
Enrollment
25
Locations
2
Arms
122.5
Anticipated Duration (Months)
5.1
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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

Study Design

Study Type:
Interventional
Anticipated Enrollment :
128 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
LOC-R01: Randomized Phase IB/II Study of Escalating Doses of Lenalidomide and Ibrutinib in Association With R-MPV as a Targeted Induction Treatment for Patients Aged 18 to 60 (up to 65 for Phase II) With a Newly Diagnosed Primary Central Nervous System Lymphoma
Actual Study Start Date :
Oct 30, 2020
Anticipated Primary Completion Date :
Jan 15, 2024
Anticipated Study Completion Date :
Jan 15, 2031

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm A: R-MPV with Lenalidomide

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

Drug: 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.
Other Names:
  • Revlimid

    		•
    Active Comparator: Arm B: R-MPV with Ibrutinib

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

    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.
    Other Names:
  • Imbruvica

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Dose Limiting Toxicity (DLT) during the first cycle of treatment for each treatment arm. [1 month]

      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

    2. Complete Response (CR) rate including unconfirmed Complete Response (uCR) at the end of the 4 cycles of induction therapy [4 months]

      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)

    Secondary Outcome Measures

    1. Response rates (CR + uCR) after 2 cycles of induction treatment [2 months]

      Assessment of response will be based on the International Primary Central Nervous System Lymphoma Collaborative Group (IPCG)

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

      Assessment of response will be based on the International Primary Central Nervous System Lymphoma Collaborative Group (IPCG)

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

      Assessment of response will be based on the International Primary Central Nervous System Lymphoma Collaborative Group (IPCG)

    4. Overall Survival (OS) [142 months]

      Overall Survival (OS) will be calculated from the date of randomization to the date of death, whatever the cause. Patients alive at the date of last contact will be censored at this date.

    5. Progression-Free Survival (PFS) [142 months]

      Progression-Free Survival (PFS) will be calculated from the date of randomization to the date of progression or death (if the patient does not progress). Patients alive without progression at the date of last contact will be censored at this date

    6. The severity of the toxicity of treatment induction or ASCT [7 months]

      Toxicity of treatment induction or ASCT will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE 5.0) whenever possible and described by system organ class, preferred term

    7. Patients who will receive ASCT [7 months]

      The percentage of patients who will receive ASCT will be presented

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

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

      1. 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):

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

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

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

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

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

    11. Able to swallow capsules.

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

    13. 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.

    14. 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.

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

    16. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 CHU Amiens Amiens France
    2 CHU Angers Angers France
    3 CHU Besançon Besançon France
    4 Institut Bergonié Bordeaux France
    5 CHU Caen Caen France
    6 CHU Clermont-Ferrand Clermont-Ferrand France
    7 CH Colmar Colmar France
    8 CHU Créteil Créteil France
    9 CHU Dijon Dijon France
    10 CHU Grenoble Grenoble France
    11 CHRU Lille Lille France 69000
    12 CHU Limoges Limoges France
    13 CHU Lyon Lyon France
    14 CHU La Timone Marseille Marseille France
    15 CHU Nancy Nancy France
    16 CHU Nantes Nantes France
    17 Centre Lacassagne Nice France
    18 Institut Curie Paris France 75005
    19 Hôpital Cochin Paris France 75006
    20 CHU Pitié-Salpêtrière Paris France 75013
    21 CHU Poitiers Poitiers France
    22 CHU Rennes Rennes France 35000
    23 Centre Henri Becquerel Rouen France 76000
    24 IUCT -Oncopole Toulouse France
    25 CHU Tours Tours France

    Sponsors and Collaborators

    • Institut Curie
    • National Cancer Institute, France

    Investigators

    • Study Director: Steven LE GOUILL, PhD, Institut Curie

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Institut Curie
    ClinicalTrials.gov Identifier:
    NCT04446962
    Other Study ID Numbers:
    • IC 2019-02
    • 2019-003632-23
    First Posted:
    Jun 25, 2020
    Last Update Posted:
    Apr 22, 2022
    Last Verified:
    Apr 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Institut Curie
    Lymphoma
    Nervous System
    Primary
    Additional relevant MeSH terms:
    Lymphoma
    Nervous System Neoplasms
    Lymphoma, Large B-Cell, Diffuse
    Central Nervous System Neoplasms
    Lenalidomide

    Study Results

    No Results Posted as of Apr 22, 2022