Lenalidomide, Bendamustine and Rituximab as First-line Therapy for Patients Over 65 Years With Mantle Cell Lymphoma.

Study Overview
=================
Brief Summary
-----------------
In phase I: Establishing maximally tolerated dose of lenalidomide in combination with bendamustine and rituximab. In phase II: Evaluation of progression free survival with treatment with lenalidomide, bendamustine and rituximab

Detailed Description
-----------------
This trial consists of both a phase I portion and a phase II portion. In phase I, the MTD of lenalidomide is determined, starting with 5 mg/day given up to maximally 25 mg/day. In combination with this treatment, bendamustine and rituximab are given at fixed doses. The phase I portion follows a sequential dose escalation, 3+3 design. Initially, three subjects are started treatment with dose regimen 1 (5 mg/day). After the third subject completed two cycles of treatment, if no DLT has occured, the next group of three subjects are treated at the next dose level of lenalidomide (10 mg/day). If one of the three initial subjects experiences a DLT, the cohort is expanded to six subjects. If less than two out of the six subjects experiences a DLT, then the next higher dose group is initiated. If two or more subjects experiences a DLT, no higher dose levels will be tested and the MTD dose has been exceeded. Additional subjects are enrolled at the MTD on the phase II portion of the trial. The above described treatment with lenalidomide, bendamustine and rituximab are given in 6 cycles, cycle length 22 days. Lenalidomide is given day 1-21, bendamustine day 1-2 and rituximab day 1. During the following maintenance treatment, single treatment with lenalidomide will be given with the same dose of lenalidomide (25 mg/day) for 7 cycles, whether in phase I or phase II portion of the trial.

Official Title
-----------------
Lenalidomide, Bendamustine and Rituximab as First-line Therapy for Patients Over 65 Years With Mantle Cell Lymphoma - a Nordic Lymphoma Group Trial

Conditions
-----------------
Mantle Cell Lymphoma

Intervention / Treatment
-----------------
* Drug: lenalidomide, bendamustine, rituximab
* Drug: lenalidomide, bendamustine, rituximab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age over 65 years, or age under 65 years, unable to tolerate high dose chemotherapy with autologous stem cell support Histologically confirmed mantle cell lymphoma, stage II-IV at time of diagnosis No previous treatment for lymphoma except radiotherapy or one cycle of any chemotherapy regimen for lymphoma WHO Performance Status 0-3 Written informed concent Female subjects of childbearing potential must agree to use and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, through study drug therapy and for 4 weeks after the end of study drug therapy Male subjects must agree to use condoms throughout study drug therapy if their partner is of childbearing potential, and has no contraception, and agree to not donate semen during study drug therapy and for one week after end of study drug therapy All subjects must agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation, and agree not to share study medication with another person Exclusion Criteria: Impaired liver function ANC less than 1.0 x 10 9, unless caused by bone marrow infiltration by lymphoma Platelet count less than 60 x 10 9, unless caused by bone marrow infiltration by lymphoma Creatinine clearance below 50 ml/min (cockcroft formula)) Known HIV positivity Known seropositivity for HCV, HBsAG, anti-HBc, or other active infection uncontrolled by treatment Psychiatric illness or condition which could interfere with the subject´s ability to understand the requirements of the study Requirement of corticosteroid therapy at a dose over 10 mg prednisolone/day Pregnant or lactating females

Ages Eligible for Study
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lenalidomide, bendamustine, rituximab<br> | Drug: lenalidomide, bendamustine, rituximab<br>* Phase I: Maximally tolerable dose of lenalidomide will be determined, starting with 5 mg per day, and up to maximally 25 mg per day. This treatment is given in combination with bendamustine and rituximab. Phase II: Determination of progression free survival with treatment with lenalidomide (dosing determined in phase I) in combination with bendamustine and rituximab.<br>Drug: lenalidomide, bendamustine, rituximab<br>* lenalidomide: day 1-21, maximum 13 cycles bendamustine: days 1-2, cycle 1-6 rituximab: day1, cycle 1-6<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD of lenalidomide (phase I) Progression free survival (phase II) |  | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Mantle cell lymphoma, Lenalidomide, Bendamustine, Rituximab, Nordic Lymphoma Group, MTD for lenalidomide, Untreated patients, Patients with mantle cell lymphoma, age over 65 years