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

Mantle Cell Lymphoma Clinical Trial

— LENA-BERIT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00963534
• Other study ID #: NLG-MCL4
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 20, 2009
• Last updated: March 9, 2018
• Start date: September 2009
• Est. completion date: August 2017

Study information

• Verified date: March 2018
• Source: Lund University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: August 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma

Intervention

Drug:
• lenalidomide, bendamustine, rituximab
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.
• lenalidomide, bendamustine, rituximab
lenalidomide: day 1-21, maximum 13 cycles bendamustine: days 1-2, cycle 1-6 rituximab: day1, cycle 1-6

Locations

Country	Name	City	State
Denmark	Århus University Hospital	Århus
Denmark	Herlev Hospital	Copenhagen
Denmark	Rigshospitalet, Department of Hematology	Copenhagen
Finland	Helsinki University Central Hospital	Helsinki
Norway	Haukeland University Hospital, Department of Oncology	Bergen
Norway	Norwegian Radium Hospital	Oslo
Norway	Ulleval University Hospital, Department of Oncology	Oslo
Norway	University Hospital of Stavanger, Department of Haematology and Oncology	Stavanger
Norway	University Hospital of Tromso, Department of Oncology	Tromso
Sweden	Sahlgrenska University Hospital, Department of Hematology	Göteborg
Sweden	University Hospital Linköping, Department of Hematology	Linköping
Sweden	Sunderbyn Hospital, Department of Medicine	Luleå
Sweden	University Hospital Lund, Department of Oncology	Lund
Sweden	Karolinska University Hospital, Department of Hematology	Stockholm
Sweden	Sundsvall Hospital, Department of Medicine	Sundsvall
Sweden	University Hospital of Norrland, Department of Oncology	Umeå
Sweden	Uppsala University Hospital, Department of Oncology	Uppsala

Sponsors (4)

Lead Sponsor	Collaborator
Lund University Hospital	Celgene, Mundipharma Pte Ltd., Roche Pharma AG

Countries where clinical trial is conducted

Denmark,  Finland,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MTD of lenalidomide (phase I) Progression free survival (phase II)		2 years