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.
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
- Conditions the study is for
- Lymphoma, Large B-Cell, Diffuse, Central Nervous System Neoplasms, Primary
- 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
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
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 group | Role | What they receive |
|---|---|---|
| Arm A: R-MPV with Lenalidomide | Active comparator | Lenalidomide in association with R-MPV as a targeted induction treatment Receives: Drug: Lenalidomide |
| Arm B: R-MPV with Ibrutinib | Active comparator | Ibrutinib 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.
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
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)
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
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
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
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
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
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
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.
- First posted25 Jun 2020
- Study start30 Oct 2020
- Primary completion2 Feb 2035 (estimated)
- Study completion30 Aug 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lymphoma, Large B-Cell, DiffuseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Institut Curie
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute, France
- Responsible party
- Sponsor
- Investigators
- Steven LE GOUILL, PhD, Study director, Institut Curie
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