Clinical trial NCT00963534: Lenalidomide, Bendamustine and Rituximab as First-line Therapy for Patients Over 65 Years With Mantle Cell Lymphoma.
Official title: Lenalidomide, Bendamustine and Rituximab as First-line Therapy for Patients Over 65 Years With Mantle Cell Lymphoma - a Nordic Lymphoma Group Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Mantle Cell Lymphoma
Keywords: Mantle cell lymphoma
Lenalidomide
Bendamustine
Rituximab
Nordic Lymphoma Group
MTD for lenalidomide
Untreated patients
Patients with mantle cell lymphoma, age over 65 years
Lead sponsor: Lund University Hospital
Sponsor class: OTHER
Collaborators: name: Mundipharma Pte Ltd.
name: Celgene
name: Roche Pharma AG
First posted: 2009-08-21
Enrollment: 51
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: MTD of lenalidomide (phase I) Progression free survival (phase II)
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Herlev Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Department of Hematology
city: Århus
country: Denmark
facility: Århus University Hospital
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Bergen
country: Norway
facility: Haukeland University Hospital, Department of Oncology
city: Oslo
country: Norway
facility: Norwegian Radium Hospital
city: Oslo
country: Norway
facility: Ulleval University Hospital, Department of Oncology
city: Stavanger
country: Norway
facility: University Hospital of Stavanger, Department of Haematology and Oncology
city: Tromso
country: Norway
facility: University Hospital of Tromso, Department of Oncology
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital, Department of Hematology
city: Linköping
country: Sweden
facility: University Hospital Linköping, Department of Hematology
city: Luleå
country: Sweden
facility: Sunderbyn Hospital, Department of Medicine
city: Lund
country: Sweden
facility: University Hospital Lund, Department of Oncology
city: Stockholm
country: Sweden
facility: Karolinska University Hospital, Department of Hematology
city: Sundsvall
country: Sweden
facility: Sundsvall Hospital, Department of Medicine
city: Umeå
country: Sweden
facility: University Hospital of Norrland, Department of Oncology
city: Uppsala
country: Sweden
facility: Uppsala University Hospital, Department of Oncology
Study officials:
affiliation: University Hospital Lund, Sweden
name: Mats Jerkeman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Lund, Sweden
name: Jan Sundberg, RN
role: STUDY_DIRECTOR
References:
citation: Albertsson-Lindblad A, Kolstad A, Laurell A, Raty R, Gronbaek K, Sundberg J, Pedersen LB, Ralfkiaer E, Karjalainen-Lindsberg ML, Sundstrom C, Ehinger M, Geisler C, Jerkeman M. Lenalidomide-bendamustine-rituximab in patients older than 65 years with untreated mantle cell lymphoma. Blood. 2016 Oct 6;128(14):1814-1820. doi: 10.1182/blood-2016-03-704023. Epub 2016 Jun 27.