Chronic Lymphocytic Leukemia, Non-Hodgkin's Lymphoma
Conditions
Keywords
CLL, NHL, lymphoma
Brief summary
This study is for subjects with a B-cell lymphoid malignancy (lymphoma) or chronic lymphocytic leukemia (CLL) that has come back after or did not get better with previous treatment. The purpose of this study is to find out the highest dose of lenalidomide that can be given together with bendamustine and rituximab. The study will also look what effects the combination of lenalidomide and bendamustine and the combination of lenalidomide, bendamustine and rituximab will have on patients and their disease.
Detailed description
This is a Phase I, open-label, dose-escalation study of bendamustine and lenalidomide (BL) and also bendamustine,lenalidomide, and rituximab (BLR) in relapsed/refractory CLL and relapsed/refractory B-cell lymphomas. Phase I dose escalation will be done independently for the CLL and NHL groups. In addition, the study will be conducted in 2 parts. In part I of the study, the maximum tolerated dose of bendamustine and lenalidomide will be determined independently for the CLL and NHL groups. In part II of the study, CLL and NHL subjects will be enrolled at the MTD of BL determined in Part I for CLL and NHL and all subjects will receive rituximab. Part II of the study will determine the MTD of BLT independently for the NHL and CLL groups.
Interventions
DRUGbendamustine and lenalidomide
Lenalidomide is given daily orally for one week followed by bendamustine HCL 90 mg/m2 IV over 30 to 60 minutes on days 1 and 2 in combination with lenalidomide, given orally, in dose-escalating cohorts. After a maximum of 6 cycles of combination therapy with bendamustine and lenalidomide, lenalidomide monotherapy is continued for an additional 6 cycles as tolerated or until disease progression.
DRUGBL-NHL
Bendamustine HCL 90 mg/m2 given intravenously over 30 to 60 minutes on days 1 and 2 in combination with lenalidomide, given orally, in dose-escalating cohorts. After a maximum of 6 cycles of combination therapy with bendamustine and lenalidomide, lenalidomide monotherapy is continued for an additional 6 cycles as tolerated or until disease progression.
DRUGBLR-CLL
Lenalidomide is given orally for 7 days followed by rituximab 375 mg/m2 on day 1 in addition to bendamustine 90 mg/m2 intravenously over 30-60 minutes on days 1 and 2 and lenalidomide orally daily every 28 days for a total of 6 cycles. After 6 cycles of bendamustine, lenalidomide and rituximab, lenalidomide monotherapy is administered as continued therapy for an additional 6 cycles as tolerated or until disease progression.
DRUGBLR-NHL
Rituximab 375 mg/m2 is given on day 1 on day 1 in addition to bendamustine 90 mg/m2 intravenously over 30-60 minutes on days 1 and 2 and lenalidomide orally daily every 28 days for a total of 6 cycles. After 6 cycles of bendamustine, lenalidomide and rituximab, lenalidomide monotherapy is administered as continued therapy for an additional 6 cycles as tolerated or until disease progression.
Sponsors
Celgene Corporation
Cephalon
Georgetown University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented relapsed or refractory B-cell NHL; CD-20 positive tumor. Indolent NHL: follicular B-cell lymphoma, diffuse small lymphocytic lymphoma, lymphoplasmacytic lymphoma, marginal zone lymphoma, transformed aggressive lymphomas, mantle cell lymphoma and chronic lymphocytic leukemia * Maximum of 6 prior chemotherapy regimens. Prior rituximab is allowed. * Bidimensionally measurable disease * ECOG performance status 0-2 * Absolute neutrophil count \>/= 1000 and platelet count \>/= 50,000 * Serum creatinine \</= 1.5 mg/dL * Adequate hepatic function * Estimated life expectancy of at least 3 months * All study participants must be registered into the mandatory RevAssist program and be willing and able to comply with the requirements of RevAssist * Able to take aspirin 81 mg daily as prophylactic anticoagulation
Exclusion criteria
* Chemotherapy or immunotherapy within 3 weeks prior to entering study or failure to recover from adverse events due to any agents administered previously * Use of investigational agents within 28 days of study * Hematopoietic growth factors within 14 days of study * History of prior high dose chemotherapy with allogeneic stem cell support * History of prior radioimmunotherapy \</= 1 year * Concurrent treatment with therapeutic doses of systemic steroids * Pregnant or lactating female subjects * Concurrent, active malignancy other than lymphoma or CLL * Primary CNS lymphoma * Patients with a prior diagnosis of lymphoma active in the CNS are eligible only if CNS has been treated, and they are neurologically stable with no progressive symptoms off steroids and anti-convulsants * Serious infection, medical condition, or psychiatric condition that, in the opinion of the investigator, might interfere with the achievement of study objectives * Hypersensitivity to murine proteins or to any component of rituximab * Known positive for HIV or infectious hepatitis type C; hepatitis type B that is active and uncontrolled * Hypersensitivity to mannitol * Evidence of laboratory tumor lysis syndrome by Cairo-Bishop criteria * Subject with recent thromboembolic event (deep vein thrombosis or pulmonary embolism) unless clinically stable and event occurred more than 2 weeks prior to enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose | 2 years |
| Dose limiting toxicity | 2 years |
| Recommended Phase II dose | 2 years |
Secondary
| Measure | Time frame |
|---|---|
| overall safety profile | 2 years |
| Plasma pharmacokinetics | 2 years |
| Preliminary antitumor activity | 2 years |
Countries
United States
Outcome results
None listed