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

NCT01956695 | Completed Phase 2 DMC

• 2 other identifiers: IC 2012-052012-003786-17
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 12

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.

Conditions

Lymphoma; Relapse

Outcome Measures

Primary Outcomes (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.

  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.

  33 months

Secondary Outcomes (5)

• The safety of the association during induction and maintenance therapy in a population of PCNSL (NCI V4)

  56 months

• The duration of response

  56 months

• Progressive Free Survival at one year from the date of inclusion to the date of progression of the disease or death

  56 months

• Overall Survival from the date of inclusion to the date of death

  56 months

• Quality of life using QLQ-C30 EORTC (European Organization for Research and Treatment of Cancer) questionnaire

  20 months

Other Outcomes (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

  33 months

Study Arms (1)

Lenalidomide & Rituximab

EXPERIMENTAL

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; Drug: Rituximab

Interventions

Lenalidomide DRUG

Also known as: Revlimid®

Lenalidomide & Rituximab

Rituximab DRUG

Also known as: Mabthera®

Lenalidomide & Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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 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)
• 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 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.
• Signed inform consent

You may not qualify if:

• Contraindication to any drug contained in the chemotherapy regimen or to any of their excipients
• 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 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).
• 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
• Impossibility to follow the calendar of exams because of geographic, social or psychological reasons
• Patient under measure of legal protection

Sponsors & Collaborators

• Institut Curie: lead
• Centre Hospitalier Universitaire, Amiens: collaborator
• Institut Bergonié: collaborator
• University Hospital, Clermont-Ferrand: collaborator
• University Hospital, Lille: collaborator
• Central Hospital, Nancy, France: collaborator
• Groupe Hospitalier Pitie-Salpetriere: collaborator
• Centre Henri Becquerel: collaborator
• University Hospital, Tours: collaborator
• Centre Leon Berard: collaborator
• University Hospital, Grenoble: collaborator

Study Sites (12)

Centre Léon Bérard

Lyon, Auvergne-Rhône-Alpes, 39373, France

Location

CHU Estaing

Clermont-Ferrand, Auvergne, 63003, France

Location

CHU Bretonneau - Centre Henry Kaplan

Tours, Centre-Val de Loire, 37044, France

Location

Institut Bergonié

Bordeaux, Gironde, 33076, France

Location

Chu Michallon

Grenoble, Isère, 38043, France

Location

Hôpital Central

Nancy, Lorraine, 54036, France

Location

CHRU Lille - Hôpital Claude Huriez

Lille, Nord, 59037, France

Location

Centre Henri Becquerel

Rouen, Seine Maritime, 76038, France

Location

CHU Amiens -Hôpital Sud

Amiens, Somme, 80054, France

Location

Chu La Timone

Marseille, 13005, France

Location

Hôpital de la Pitié Salpétrière

Paris, Île-de-France Region, 75013, France

Location

Institut curie - Hôpital René Huguenin

Saint-Cloud, Île-de-France Region, 92210, France

Location

Related Publications (1)

• 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.

  PMID: 30698644 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Lymphoma; Recurrence

Interventions

Lenalidomide; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Carole SOUSSAIN, MD

  Institut Curie - Hopital Rene Huguenin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2013
• First Posted: October 8, 2013
• Study Start: September 18, 2013
• Primary Completion: January 11, 2018
• Study Completion: January 11, 2018
• Last Updated: December 17, 2020

Record last verified: 2019-07

Locations

FR (12)