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

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ClinicalTrials.gov Identifier: NCT01956695
Recruitment Status : Completed
First Posted : October 8, 2013
Last Update Posted : July 10, 2019
Sponsor:
Collaborators:
Centre Hospitalier Universitaire, Amiens
Institut Bergonié
University Hospital, Clermont-Ferrand
University Hospital, Lille
Central Hospital, Nancy, France
Groupe Hospitalier Pitie-Salpetriere
Centre Henri Becquerel
University Hospital, Tours
Centre Leon Berard
University Hospital, Grenoble
Information provided by (Responsible Party):
Institut Curie

Brief 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.


Condition or disease Intervention/treatment Phase
Lymphoma Relapse Drug: Lenalidomide Drug: Rituximab Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : September 18, 2013
Actual Primary Completion Date : January 11, 2018
Actual Study Completion Date : January 11, 2018


Arm Intervention/treatment
Experimental: 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.

Drug: Lenalidomide
Other Name: Revlimid®

Drug: Rituximab
Other Name: Mabthera®




Primary Outcome Measures :
  1. 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. [ Time Frame: 33 months ]
    The objective response rate (CR+uCR+PR) will be evaluated according to the IPCG (International Primary CNS lymphoma Collaborative Group) recommendations. Patients will have an cerebral MRI, an ophthalmological examination and a lumbar puncture at several times.


Secondary Outcome Measures :
  1. The safety of the association during induction and maintenance therapy in a population of PCNSL (NCI V4) [ Time Frame: 56 months ]
  2. The duration of response [ Time Frame: 56 months ]
  3. Progressive Free Survival at one year from the date of inclusion to the date of progression of the disease or death [ Time Frame: 56 months ]
  4. Overall Survival from the date of inclusion to the date of death [ Time Frame: 56 months ]
  5. Quality of life using QLQ-C30 EORTC (European Organization for Research and Treatment of Cancer) questionnaire [ Time Frame: 20 months ]

Other Outcome Measures:
  1. Exploration of T cells and NK (Natural Killer) cells populations in PCNSL before and after treatment to correlate possible changes of these populations with therapeutic response [ Time Frame: 33 months ]
    Pilot exploration of T cells and NK cells populations in PCNSL before and after treatment with the combination of lenalidomide-rituximab and to correlate possible changes of these populations with therapeutic response



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01956695


Locations
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France
CHU Estaing
Clermont-Ferrand, Auvergne, France, 63003
CHU Bretonneau - Centre Henry Kaplan
Tours, Centre, France, 37044
Institut Bergonié
Bordeaux, Gironde, France, 33076
Hôpital de la Pitié Salpétrière
Paris, Ile De France, France, 75013
Institut curie - Hôpital René Huguenin
Saint-Cloud, Ile De France, France, 92210
Chu Michallon
Grenoble, Isère, France, 38043
Hôpital Central
Nancy, Lorraine, France, 54036
CHRU Lille - Hôpital Claude Huriez
Lille, Nord, France, 59037
Centre Léon Bérard
Lyon, Rhône-Alpes, France, 39373
Centre Henri Becquerel
Rouen, Seine Maritime, France, 76038
CHU Amiens -Hôpital Sud
Amiens, Somme, France, 80054
Chu La Timone
Marseille, France, 13005
Sponsors and Collaborators
Institut Curie
Centre Hospitalier Universitaire, Amiens
Institut Bergonié
University Hospital, Clermont-Ferrand
University Hospital, Lille
Central Hospital, Nancy, France
Groupe Hospitalier Pitie-Salpetriere
Centre Henri Becquerel
University Hospital, Tours
Centre Leon Berard
University Hospital, Grenoble
Investigators
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Principal Investigator: Carole SOUSSAIN, MD Institut Curie - Hopital Rene Huguenin

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Institut Curie
ClinicalTrials.gov Identifier: NCT01956695     History of Changes
Other Study ID Numbers: IC 2012-05
2012-003786-17 ( EudraCT Number )
First Posted: October 8, 2013    Key Record Dates
Last Update Posted: July 10, 2019
Last Verified: July 2019
Additional relevant MeSH terms:
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Lymphoma
Recurrence
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease Attributes
Pathologic Processes
Rituximab
Lenalidomide
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors