Efficacy of Lenalidomide With Rituximab in Refractory or Relapse of Primary Central Nervous System Lymphoma
Lymphoma - Relapse - Lenalidomide - Rituximab
Conditions: official terms
Study Type
Study Phase
Phase 2
Study Design
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: Lenalidomide Type: Drug
Name: Rituximab Type: Drug
Overall Status
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
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- 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)

- Patients can have received radiotherapy or intensive chemotherapy with hematopoietic stem cell rescue as part of treatment of the PCNSL or IOL

- Patients over 18 years old with a refractory or relapse IOL (Intra Ocular Lymphoma) and who have received either intravenous high dose methotrexate (> 1.5 g/m2) or intraocular methotrexate

- Life expectancy > 2 months

- Able to swallow capsules (stomach tube not allowed)

- Adequate bone marrow function with absolute leukocytes > 2000/mm3, neutrophil count (ANC) > 1000/mm3, haemoglobin > 8 g/dl and platelets > 100 000/mm3

- Adequate hepatic function with AST (aspartate aminotransferase) or ALT (alanine aminotranferase) < 3 times the upper limit of normal (ULN), bilirubin < 1.5 x ULN (except in cases of haemolytic anemia or Gilbert's syndrome)

- 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)

- Patient aged 18 years old or more and without measure of legal protection

- Able to understand teratogenic risks of the treatment

- 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 and for at least 4 weeks after discontinuation treatment with lenalidomide and one year after cessation of treatment with rituximab. Pregnancy test (βHCG amount) must be negative at the inclusion 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 including any interruption of catches and 4 weeks after the end of treatment.

- Signed inform consent

Exclusion Criteria:

- Any severe infection and/or active (eg tuberculosis, sepsis and opportunistic infections), immune deficiency and hypersensitivity to any drug contained in the chemotherapy regimen or to any of their excipients (including lactose intolerance

- T-cell lymphoma

- Diagnosis of any second malignancy within the last 5 years

- Prior history of organ transplantation or other cause of severe immunodeficiency

- History of cardiac and /or impaired cardiac function disorders (ECG QTc (corrected QT interval)>450 msec, congenital long QT syndrome, history of ventricular tachyarrhythmias, ventricular fibrillation or simply "torsade", congestive heart failure NYHA (New York Heart Association)III/IV, uncontrolled hypertension)

- Known HIV infection or active hepatitis B or HCV (hepatitis C virus) infection of less than 4 weeks

- Inclusion in another experimental anti-cancer drug therapy

- Impossibility to follow the calendar of exams because of geographic, social or psychological reasons

- Patient under guardianship

- No social security
CHU Estaing
Clermont-Ferrand, Auvergne, France
Status: Recruiting
Contact: Cécile Molucon-Chabrot, MD - cchabrot@chu-clermontferrand.fr
CHU Bretonneau - Centre Henry Kaplan
Tours, Centre, France
Status: Recruiting
Contact: emmanuel gyan, MD - emmanuel.gyan@univ-tours.fr
Institut Bergonié
Bordeaux, Gironde, France
Status: Recruiting
Contact: Anna Schmitt, Phd - a.schmitt@bordeaux.unicancer.fr
Hôpital de la Pitié Salpétrière
Paris, Ile de France, France
Status: Recruiting
Contact: Sylvain Choquet, MD - sylvain.choquet@psl.aphp.fr
Institut curie - Hôpital René Huguenin
Saint-Cloud, Ile de France, France
Status: Recruiting
Contact: Carole Soussain, MD - +33147111515 - carole.soussain@curie.net
Chu Michallon
Grenoble, Isère, France
Status: Recruiting
Contact: Rémy Gressin, MD - RGressin@chu-grenoble.fr
Hôpital Central
Nancy, Lorraine, France
Status: Recruiting
Contact: Patrick Beauchesne, MD - +331383851688 - p.beauchesne@chu-nancy.fr
CHRU Lille - Hôpital Claude Huriez
Lille, Nord, France
Status: Recruiting
Contact: Franck Morschhauser, MD - franck.morschhauser@chru-lille.fr
Centre Léon Bérard
Lyon, Rhône-Alpes, France
Status: Recruiting
Contact: Hervé Ghesquières, MD - herve.ghesquieres@lyon.unicancer.fr
Centre Henri Becquerel
Rouen, Seine Maritime, France
Status: Active, not recruiting
CHU Amiens -Hôpital Sud
Amiens, Somme, France
Status: Recruiting
Contact: Ghandi Laurent Damaj, MD - damaj.gandhi@chu-amiens.fr
Start Date
September 2014
Completion Date
May 2018
Institut Curie
Institut Curie
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page