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Unconsciousness

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Nervous System Neoplasms

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Lymphoproliferative Disorders

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Immunoproliferative Disorders

Lymphoma, B-Cell

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Primary Central Nervous System Lymphoma

B-cell Lymphoma

Antineoplastic Agents

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Dermatologic Agents

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All Drugs and Chemicals

Amino Acids

Methotrexate

Rituximab

Vincristine

Lenalidomide

Ibrutinib

Procarbazine

Immunologic Factors

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Tyrosine Kinase Inhibitors

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Tyrosine

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

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

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.

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.

Carole SOUSSAIN, MD

LYNDA CORVI

Caroline DELETTE, MD

Jérôme PAILLASSA, MD

Sophie BERNARD, MD

Adrien CHAUCHET, MD

Anna SCHMITT, MD

Gandhi DAMAJ, MD

Gandhi DAMAJ, PhD

Cécile MOLUCON-CHABROT, MD

Guido AHLE, MD

Guido AHLE Guido AHLE, MD

Louise ROULIN, MD

Rémy Rémy GRESSIN, MD

Rémy GRESSIN, MD

Franck MORSCHHAUSER, PhD

Julie ABRAHAM, MD

ABRAHAM Julie, MD

Hervé GHESQUIERES, MD

Hervé GHESQUIERES, Phd

Olivier CHINOT, MD

Luc TAILLANDIER, PhD

Thomas GASTINNE, MD

Frédéric PEYRADE, MD

Agathe WAULTIER-RASCALOU, MD

Carole Soussain, MD

Lise WILLEMS, MD

Caroline HOUILLIER, MD

Vincent DELWAIL, MD

Thierry LAMY De La CHAPELLE, PhD

Thierry Thierry LAMY De La CHAPELLE, PhD

Fabrice JARDIN, PhD

Marie DE CHARETTE, MD

Luc-Mathieu FORNECKER, MD

Lucie Obéric, MD

Emmanuel GYAN, MD

Steven LE GOUILL, PhD

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).

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

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

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

Sponsor will share de-identified data sets generated under the project will be disseminated in accordance with Institut Curie policies.

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

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)

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

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.

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

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

The percentage of patients who will receive ASCT will be presented

National Cancer Institute, France

Institut Curie

portable device which produces electrical fields

Optune TTF device

This study will compare the overall survival (OS) time of elderly patients who would not tolerate standard chemotherapy for PCNSL treated with WBXRT together with Optune-TTF to those treated with whole-brain radiotherapy alone.

Standard treatment of primary central nervous system lymphoma (PCNSL) for patients with good performance status involves high-dose methotrexate-based chemotherapy regimens and whole-brain radiation therapy (WBXRT). Although up to 20% of patients with PCNSL are 80 years of age or older, little data exist with regard to optimal treatment of this patient population and they often do not qualify for clinical trials. In addition, elderly patients have a poorer rate of complete and partial response and increased risk of toxicity when treated with standard chemotherapy regimens. Though a consensus does not exist, radiotherapy alone is often used in these patients to minimize toxic effects of more aggressive chemotherapies.

The Optune TTF device has proven effective in treating high-grade gliomas and is currently being investigated to treat meningiomas and metastatic lesions in the brain as well as other tumor types elsewhere in the body. It is generally well tolerated with no known systemic side effects, producing only an occasional local skin reaction. The mechanism of action is independent of tumor type and therefore may be effective in treating lymphoma as well.

prospective group (non-randomized) compared to historical matched controls

Use of Optune TTF With Radiation as an Alternative for Elderly Patients With Primary CNS Lymphoma

use of concomitant steroids and antiepileptic use

NovoCure Ltd.

Saint Luke's Health System

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
LOC-R01 Study of Lenalidomide and Ibrutinib in Association With Rituximab-Methotrexate Procarbazine Vincristin (R-MPV)	NCT04446962	Lymphoma, Large... Central Nervous...	Lenalidomide Ibrutinib	18 Years - 65 Years	Institut Curie
Use of Optune TTF With Radiation as an Alternative for Elderly Patients With Primary CNS Lymphoma	NCT03530605	Central Nervous...	Optune TTF devi...	70 Years -	Saint Luke's Health System

Spots Global Cancer Trial Database for central nervous system neoplasms, primary