Efficacy of Lenalidomide With Rituximab in Refractory or Relapse of Primary Central Nervous System Lymphoma
Information source: Institut Curie
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Lymphoma; Relapse; Lenalidomide; Rituximab
Intervention: Lenalidomide (Drug); Rituximab (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: Institut Curie Official(s) and/or principal investigator(s): Carole SOUSSAIN, MD, Principal Investigator, Affiliation: Institut Curie - Hopital Rene Huguenin
Overall contact: Patricia TRESCA, UGEC Leader, Phone: 33156245630, Email: patricia.tresca@curie.net
Summary
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.
Clinical Details
Official title: Phase II Study Evaluating the Efficacy of Lenalidomide in Association With Rituximab in Refractory or Relapse of Primary Central Nervous System Lymphoma (PCNSL)
Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Assess the efficacy of lenalidomide in combination with rituximab in relapsed/refractory PCNSL as measured by the objective response rate (CR + uCR + PR) at the end of the 8 cycles of induction therapy.
Secondary outcome: The safety of the association during induction and maintenance therapy in a population of PCNSL (NCI V4)The duration of response Progressive Free Survival at one year from the date of inclusion to the date of progression of the disease or death Overall Survival from the date of inclusion to the date of death Quality of life using QLQ-C30 EORTC (European Organization for Research and Treatment of Cancer) questionnaire
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): 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
Locations and Contacts
Patricia TRESCA, UGEC Leader, Phone: 33156245630, Email: patricia.tresca@curie.net
CHU Estaing, Clermont-Ferrand, Auvergne 63003, France; Recruiting Cécile Molucon-Chabrot, MD, Email: cchabrot@chu-clermontferrand.fr Cécile Molucon-Chabrot, MD, Principal Investigator
CHU Bretonneau - Centre Henry Kaplan, Tours, Centre 37044, France; Recruiting emmanuel gyan, MD, Email: emmanuel.gyan@univ-tours.fr Emmanuel Gyan, MD, Principal Investigator
Institut Bergonié, Bordeaux, Gironde 33076, France; Recruiting Anna Schmitt, Phd, Email: a.schmitt@bordeaux.unicancer.fr Anna Schmitt, MD, Principal Investigator
Hôpital de la Pitié Salpétrière, Paris, Ile de France 75013, France; Recruiting Sylvain Choquet, MD, Email: sylvain.choquet@psl.aphp.fr Sylvain Choquet, MD, Principal Investigator
Institut curie - Hôpital René Huguenin, Saint-Cloud, Ile de France 92210, France; Recruiting Carole Soussain, MD, Phone: +33147111515, Email: carole.soussain@curie.net Carole Soussain, MD, Principal Investigator
Chu Michallon, Grenoble, Isère 38043, France; Recruiting Rémy Gressin, MD, Email: RGressin@chu-grenoble.fr Rémy Gressin, MD, Principal Investigator
Hôpital Central, Nancy, Lorraine 54036, France; Recruiting Patrick Beauchesne, MD, Phone: +331383851688, Email: p.beauchesne@chu-nancy.fr Pactrick Beauchesne, MD, Principal Investigator
CHRU Lille - Hôpital Claude Huriez, Lille, Nord 59037, France; Recruiting Franck Morschhauser, MD, Email: franck.morschhauser@chru-lille.fr Franck Morschhauser, MD, Principal Investigator
Centre Léon Bérard, Lyon, Rhône-Alpes 39373, France; Recruiting Hervé Ghesquières, MD, Email: herve.ghesquieres@lyon.unicancer.fr Hervé Ghesquieres, MD, Principal Investigator
Centre Henri Becquerel, Rouen, Seine Maritime 76038, France; Active, not recruiting
CHU Amiens -Hôpital Sud, Amiens, Somme 80054, France; Recruiting Ghandi Laurent Damaj, MD, Email: damaj.gandhi@chu-amiens.fr Gandhi Damaj, MD, Principal Investigator
Additional Information
Starting date: September 2014
Last updated: September 5, 2014
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