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

Lymphoma Clinical Trial

— REVRI  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01956695
• Other study ID #: IC 2012-05
• Secondary ID: 2012-003786-17
• Status: Completed
• Phase: Phase 2
• Start date: September 18, 2013
• Est. completion date: January 11, 2018

Study information

• Verified date: July 2019
• Source: Institut Curie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: January 11, 2018
• Est. primary completion date: January 11, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Lymphoma
• Recurrence
• Relapse

Intervention

Drug:
• Lenalidomide

• Rituximab

Locations

Country	Name	City	State
France	CHU Amiens -Hôpital Sud	Amiens	Somme
France	Institut Bergonié	Bordeaux	Gironde
France	CHU Estaing	Clermont-Ferrand	Auvergne
France	Chu Michallon	Grenoble	Isère
France	CHRU Lille - Hôpital Claude Huriez	Lille	Nord
France	Centre Léon Bérard	Lyon	Rhône-Alpes
France	Chu La Timone	Marseille
France	Hôpital Central	Nancy	Lorraine
France	Hôpital de la Pitié Salpétrière	Paris	Ile De France
France	Centre Henri Becquerel	Rouen	Seine Maritime
France	Institut curie - Hôpital René Huguenin	Saint-Cloud	Ile De France
France	CHU Bretonneau - Centre Henry Kaplan	Tours	Centre

Sponsors (11)

Lead Sponsor	Collaborator
Institut Curie	Central Hospital, Nancy, France, Centre Henri Becquerel, Centre Hospitalier Universitaire, Amiens, Centre Leon Berard, Groupe Hospitalier Pitie-Salpetriere, Institut Bergonié, University Hospital, Clermont-Ferrand, University Hospital, Grenoble, University Hospital, Lille, University Hospital, Tours

Country where clinical trial is conducted

France, 

References & Publications (1)

Ghesquieres H, Chevrier M, Laadhari M, Chinot O, Choquet S, Moluçon-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, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	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	33 months
Primary	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	The safety of the association during induction and maintenance therapy in a population of PCNSL (NCI V4)		56 months
Secondary	The duration of response		56 months
Secondary	Progressive Free Survival at one year from the date of inclusion to the date of progression of the disease or death		56 months
Secondary	Overall Survival from the date of inclusion to the date of death		56 months
Secondary	Quality of life using QLQ-C30 EORTC (European Organization for Research and Treatment of Cancer) questionnaire		20 months

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