Efficacy of Lenalidomide With Rituximab in Refractory or Relapse of Primary Central Nervous System Lymphoma

NCT ID: NCT01956695

Last Updated: 2020-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-09-18

Study Completion Date

2018-01-11

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Because Primary Central Nervous System Lymphoma (PCNSL) are mainly diffuse large B-cell lymphoma of the activated B cells (ABC) type, the investigators hypothesize that the synergy of lenalidomide with rituximab shown in systemic non-Hodgkin's lymphoma (NHL) could be observed in PCNSL.

This study will assess the efficiency of the the combination of lenalidomide and rituximab in relapsed/refractory PCNSL, and the efficiency of a maintenance treatment with lenalidomide alone in maintaining the response.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The investigators use a two-stage Fleming's design based on the following hypotheses under treatment: 10% (null hypothesis, minimal clinical benefit rate), 30% (alternative hypothesis, acceptable clinical benefit rate), 3% type I error rate, 5% type II error rate. Under these hypotheses, a total of 45 assessable patients will be necessary: 22 for the first stage + 23 for the second stage.

Stage 1: following the inclusion of the first 22 assessable patients, if 0 or 1 patient has an objective response (CR, Complete Response + uCR, unconfirmed Complete Response + PR, Partial Response) at the end of induction treatment, the study would be terminated early and the treatment will be considered ineffective. If 2 or more patients have an objective response at the end of induction treatment, then the treatment will be considered as effective in this indication. Otherwise, the second group of 23 patients will be recruited.

Stage 2: if at the end of recruitment, 8 or less patients have an objective response, the investigators will conclude to inefficacy, and if 9 or more patients have an objective response, then the treatment will be considered as effective and need further exploration.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Lymphoma Relapse

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Lenalidomide & Rituximab

Induction treatment : Lenalidomide 20 mg capsule on days 1 to 21 days of a 28 days cycle for the first cycle followed by 25 mg on daily on days 1 to 21 of a 28 days cycle for cycles 2 to 8 (in the absence of hematologic toxicity. Rituximab at day 1 of each induction course 375 mg/m² intravenous.

Maintenance : Lenalidomide 10 mg capsule on days 1 to 21 days of a 28 days cycle for 1 year or until progression or intolerance.

Group Type EXPERIMENTAL

Lenalidomide

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Lenalidomide

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Revlimid® Mabthera®

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Patients over 18 years old with a refractory or relapse PCNSL and who have previously received at least high dose methotrexate (\> 1.5 g/m²) and high dose cytarabine (2 g/m²).
2. Patients can have received radiotherapy or intensive chemotherapy with hematopoietic stem cell rescue as part of treatment of the PCNSL or IOL
3. Patients over 18 years old with a refractory or relapse IOL and who have received either intravenous high dose methotrexate (\> 1.5 g/m2) or intraocular methotrexate
4. Life expectancy \> 2 months
5. Able to swallow capsules (stomach tube not allowed)
6. Adequate bone marrow function with absolute leukocytes \> 2000/mm3, neutrophil count (ANC) \> 1000/mm3, haemoglobin \> 8 g/dl and platelets \> 100 000/mm3
7. Adequate liver function with Serum SGOT/AST or SGPT/ALT \< 3.0 X Upper Limit of Normal ULN ; bilirubin \< 1.5 X LNS (excepted in case of hemolytic anemia or Gilbert's syndrome)
8. Calculated creatinine clearance \> 40 ml/min. Patients with calculated creatinine clearance between 40 and 50ml/min lenalidomide dose will be adjusted as follows (10mg once daily)
9. Patient aged 18 years old or more and without measure of legal protection
10. Able to understand teratogenic risks of the treatment
11. Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual contact during the following time periods related to this study for at least four weeks before starting study drug, while participating in the studyand for at least 4 weeks after discontinuation of Lenalidomide and 1 year after Rituximab.. Pregnancy tests (serum β-HCG dosage) will be negative at baseline and during the study. Men must agree not to procreate a child and use condoms if their partner can procreate, during all the treatment period, during dose interruptions and for at least 4 weeks after study drug discontinuation.
12. Signed inform consent

Exclusion Criteria

1. Contraindication to any drug contained in the chemotherapy regimen or to any of their excipients
2. T-cell lymphoma
3. Diagnosis of any second malignancy within the last 5 years
4. Prior history of organ transplantation or other cause of severe immunodeficiency
5. History of heart disease and/or impaired cardiac function (ECG QTc\>450msec, congenital long QT syndrome, history of ventricular tachyarrhythmia, ventricular fibrillation, congestive heart failure NYHA III/IV, uncontrolled hypertension).
6. Known HIV or HTLV-1 infection, positive serology to HB surface antigen \[HBsAg\] or total HB core antibody \[anti-HB-c\]) and Hepatitis C (Hepatitis C virus \[HCV\] antibody) not older than 4 weeks
7. Inclusion in another experimental anti-cancer drug therapy\*
8. Impossibility to follow the calendar of exams because of geographic, social or psychological reasons
9. Patient under measure of legal protection
10. No social security \*For ethical reasons, the exclusion period within which the patient cannot be included in another trial will not be defined but discussed on a case to case basis.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Centre Hospitalier Universitaire, Amiens

OTHER

Sponsor Role collaborator

Institut Bergonié

OTHER

Sponsor Role collaborator

University Hospital, Clermont-Ferrand

OTHER

Sponsor Role collaborator

University Hospital, Lille

OTHER

Sponsor Role collaborator

Central Hospital, Nancy, France

OTHER

Sponsor Role collaborator

Groupe Hospitalier Pitie-Salpetriere

OTHER

Sponsor Role collaborator

Centre Henri Becquerel

OTHER

Sponsor Role collaborator

University Hospital, Tours

OTHER

Sponsor Role collaborator

Centre Leon Berard

OTHER

Sponsor Role collaborator

University Hospital, Grenoble

OTHER

Sponsor Role collaborator

Institut Curie

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Carole SOUSSAIN, MD

Role: PRINCIPAL_INVESTIGATOR

Institut Curie - Hopital Rene Huguenin

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Centre Léon Bérard

Lyon, Auvergne-Rhône-Alpes, France

Site Status

CHU Estaing

Clermont-Ferrand, Auvergne, France

Site Status

CHU Bretonneau - Centre Henry Kaplan

Tours, Centre-Val de Loire, France

Site Status

Institut Bergonié

Bordeaux, Gironde, France

Site Status

Chu Michallon

Grenoble, Isère, France

Site Status

Hôpital Central

Nancy, Lorraine, France

Site Status

CHRU Lille - Hôpital Claude Huriez

Lille, Nord, France

Site Status

Centre Henri Becquerel

Rouen, Seine Maritime, France

Site Status

CHU Amiens -Hôpital Sud

Amiens, Somme, France

Site Status

Chu La Timone

Marseille, , France

Site Status

Hôpital de la Pitié Salpétrière

Paris, Île-de-France Region, France

Site Status

Institut curie - Hôpital René Huguenin

Saint-Cloud, Île-de-France Region, France

Site Status

Countries

Review the countries where the study has at least one active or historical site.

France

References

Explore related publications, articles, or registry entries linked to this study.

Ghesquieres H, Chevrier M, Laadhari M, Chinot O, Choquet S, Molucon-Chabrot C, Beauchesne P, Gressin R, Morschhauser F, Schmitt A, Gyan E, Hoang-Xuan K, Nicolas-Virelizier E, Cassoux N, Touitou V, Le Garff-Tavernier M, Savignoni A, Turbiez I, Soumelis V, Houillier C, Soussain C. Lenalidomide in combination with intravenous rituximab (REVRI) in relapsed/refractory primary CNS lymphoma or primary intraocular lymphoma: a multicenter prospective 'proof of concept' phase II study of the French Oculo-Cerebral lymphoma (LOC) Network and the Lymphoma Study Association (LYSA)dagger. Ann Oncol. 2019 Apr 1;30(4):621-628. doi: 10.1093/annonc/mdz032.

Reference Type RESULT
PMID: 30698644 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2012-003786-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IC 2012-05

Identifier Type: -

Identifier Source: org_study_id