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Lymphoma, Large B-Cell, DiffusePhase 1/2LOC-R01NCT04446962

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

A Phase 1/2 study testing Lenalidomide and Ibrutinib in people with Lymphoma, Large B-Cell, Diffuse and Central Nervous System Neoplasms, Primary, run by Institut Curie at 28 sites in France.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Lenalidomide and Ibrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
118 participants
Where
28 sitesFrance
Study dates
30 Oct 2020to 30 Aug 2035
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • Adequate hematological, renal and hepatic function (Laboratory Parameters realized within 14 days before inclusion):
  • Absolute neutrophil count (ANC) >1000/mm3
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  • 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.
  • Women of childbearing potential (WCBP)* must have a negative serum (beta-human chorionic gonadotropin [B-hCG]) or urine pregnancy test at inclusion.
  • 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.

Who cannot join

  • 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).
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  • 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.
  • History of stroke or intracranial hemorrhage (except minor post biopsy hemorrhage) within 6 months prior to inclusion.
  • 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.
  • Inclusion in another experimental anti-cancer drug therapy.
  • No social security affiliation.
  • Persons under legal protection.

Trial locations and contacts

28 sites in 1 country.

28 sites in 1 country

France28 sites

  • CHU Amiens

    Amiens

  • CHU Angers

    Angers

  • CH côte Basque

    Bayonne, 64100

  • CHU Besançon

    Besançon

  • Institut Bergonié

    Bordeaux

  • CHU Caen

    Caen

  • CHU Clermont-Ferrand

    Clermont-Ferrand

  • CH Colmar

    Colmar

  • CHU Créteil

    Créteil

  • CHU Dijon

    Dijon

  • CHU Grenoble

    Grenoble

  • CHRU Lille

    Lille, 69000

  • CHU Limoges

    Limoges

  • CHU Lyon

    Lyon

  • CHU La Timone Marseille

    Marseille

  • CHU Nancy

    Nancy

  • CHU Nantes

    Nantes

  • Centre Lacassagne

    Nice

  • CHU Nîmes - Carémeau

    Nîmes, 30029

  • Institut Curie

    Paris, 75005

  • Hôpital Cochin

    Paris, 75006

  • CHU Pitié-Salpêtrière

    Paris, 75013

  • CHU Poitiers

    Poitiers

  • CHU Rennes

    Rennes, 35000

  • Centre Henri Becquerel

    Rouen, 76000

  • CHU Strasbourg-Hôpital Hautepierre

    Strasbourg, 67098

  • IUCT -Oncopole

    Toulouse

  • CHU Tours

    Tours

Other trials in France

About this study

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

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).

Read the 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

Being tested
Lenalidomide, Ibrutinib
Keywords
Lymphoma, Nervous System, Primary
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Central Nervous System Neoplasms, Lymphoma, Neurologic Manifestations

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LenalidomideDrug

    Also called Revlimid

    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.

  • IbrutinibDrug

    Also called Imbruvica

    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.

Study groups in NCT04446962
Study groupRoleWhat they receive
Arm A: R-MPV with LenalidomideActive comparatorLenalidomide in association with R-MPV as a targeted induction treatment
Receives: Drug: Lenalidomide
Arm B: R-MPV with IbrutinibActive comparatorIbrutinib in association with R-MPV as a targeted induction treatment
Receives: Drug: Ibrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 1 month

  2. 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)

    Measured: 4 months

Secondary outcomes (7)

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

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

    Measured: 2 months

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

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

    Measured: 2 months

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

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

    Measured: 4 months

  4. Overall Survival (OS)

    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.

    Measured: 142 months

  5. Progression-Free Survival (PFS)

    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

    Measured: 142 months

  6. The severity of the toxicity of treatment induction or ASCT

    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

    Measured: 7 months

  7. Patients who will receive ASCT

    The percentage of patients who will receive ASCT will be presented

    Measured: 7 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jun 2020
  2. Study start30 Oct 2020
  3. Primary completion2 Feb 2035 (estimated)
  4. Study completion30 Aug 2035 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
118 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04446962
Sponsor's protocol ID
IC 2019-02
Other IDs
2019-003632-23, 2019
Acronym
LOC-R01
Status last verified
Oct 2026
First submitted
22 Jun 2020
Last updated
19 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Sponsor will share de-identified data sets generated under the project will be disseminated in accordance with Institut Curie policies.

Publications

  • 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.

    PubMed 39300447

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Lenalidomide and Ibrutinib in people with Lymphoma, Large B-Cell, Diffuse and Central Nervous System Neoplasms, Primary, run by Institut Curie at 28 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicity (DLT) during the first cycle of treatment for each treatment arm. (time frame: 1 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04446962, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.

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