Nonmyeloablative Stem Cell Transplantation With or Without Lenalidomide for Chronic Lymphocytic Leukemia (RV-CLL-PI-0294)
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 39
- Locations
- 1
- Primary Endpoint
- Immunomanipulation After Non-myeloablative Stem Cell Transplantation for CLL (Chronic Lymphocytic Leukemia).
Study Overview
Brief Summary
The goal of this clinical research study is to learn if lenalidomide, when given with a stem cell transplant and chemotherapy (bendamustine, fludarabine, and rituximab), can help to control CLL. The safety of this treatment combination will also be studied.
Detailed Description
The Study Drugs Lenalidomide is designed to change the body's immune system. It may also interfere with the development of tiny blood vessels that help support tumor growth. Therefore, in theory, it may decrease or prevent the growth of cancer cells.
Bendamustine is designed to damage and destroy the DNA (genetic material) of cancer cells.
Fludarabine is designed to make cancer cells less able to repair damaged DNA (the genetic material of cells). This may increase the likelihood of the cells dying.
Rituximab is designed to attach to leukemia cells, which may cause them to die.
Before receiving the study drugs, 21 or more days must have passed since your last biological therapy, chemotherapy, radiotherapy, or other investigational therapy.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 18-75 years at the time of signing the informed consent form.
- •Disease: CLL in relapse, after failing conventional chemo-antibody combination therapy; CLL patients who failed to achieve CR with frontline conventional chemo-antibody; CLL patients with 17p deletion; CLL in Richter's.
- •Able to adhere to the study visit schedule and other protocol requirements.
- •Donor: HLA compatible related (HLA-A,-B,-DRBI matched or with one-antigen mismatched) or HLA compatible unrelated.
- •ECOG performance status of </= 2 at study entry
- •FEV1, FVC and DLCO >/= 40%.
- •Left ventricular EF > 40% with no uncontrolled arrhythmias or symptomatic heart disease.
- •Serum creatinine </= 1.6 mg/dL. Serum bilirubin < 1.6 mg/dL.
- •SGPT < 2x upper limit of normal.
- •Voluntary signed, written IRB-approved informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- •All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 3 weeks prior to treatment in this study.
- •Disease free of prior malignancies for >/= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast.
- •Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to study entry.
- •Disease must be chemosensitive (ie, patients must have PR or better based on CT Scans, PET Scan, and bone marrow biopsy).
- •Patients suspected to have Richter's transformation (such as elevated LDH) and/or who are PET positive, should have a lymph node biopsy to assess histological status of the disease
- •Patients must be off of alemtuzumab for 6 weeks prior to consenting.
Exclusion Criteria
- •Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- •Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
- •Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- •Use of any other experimental drug or therapy within 28 days of baseline.
- •Known hypersensitivity to thalidomide, lenalidomide, bendamustine, fludarabine. For patients will unrelated donors: Known hypersensitivity to thymoglobulin.
- •The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
- •Concurrent use of other anti-cancer agents or treatments.
- •Known positive for HIV or infectious hepatitis, type A, B or C.
- •Sinuses should be evaluated by either CT neck or CT sinuses to exclude infections
- •Deep-vein thrombosis or pulmonary embolism within 3 months of study entry.
- •History of serious infection requiring hospitalization within the last 3 months of consenting.
Arms & Interventions
Group 1: Lenalidomide
Chemotherapy, Plus Lenalidomide - Lenalidomide starting dose 5 mg by mouth every other day; increase to 5 mg/d daily in 4-5 weeks for 6 - 12 months. Fludarabine 30 mg/m^2 intravenously daily on days -5, -4, -3. Rituximab 375 mg/m2 intravenously on day -13, and 1000 mg/m^2 on days -6, +1 and +8. Thymoglobulin 1.0 mg/kg intravenously over 4 hours (day -2 and -1). On Day 0, donor blood stem cells collected will be transplanted over 30-45 minutes. Bendamustine 130 mg/m2/day by vein daily on day -5, -4, -3 (following Fludarabine). Allopurinol 300 mg by mouth daily beginning at the start of lenalidomide therapy and continuing for 3 months.
Intervention: Lenalidomide (Drug)
Group 1: Lenalidomide
Chemotherapy, Plus Lenalidomide - Lenalidomide starting dose 5 mg by mouth every other day; increase to 5 mg/d daily in 4-5 weeks for 6 - 12 months. Fludarabine 30 mg/m^2 intravenously daily on days -5, -4, -3. Rituximab 375 mg/m2 intravenously on day -13, and 1000 mg/m^2 on days -6, +1 and +8. Thymoglobulin 1.0 mg/kg intravenously over 4 hours (day -2 and -1). On Day 0, donor blood stem cells collected will be transplanted over 30-45 minutes. Bendamustine 130 mg/m2/day by vein daily on day -5, -4, -3 (following Fludarabine). Allopurinol 300 mg by mouth daily beginning at the start of lenalidomide therapy and continuing for 3 months.
Intervention: Fludarabine (Drug)
Group 1: Lenalidomide
Chemotherapy, Plus Lenalidomide - Lenalidomide starting dose 5 mg by mouth every other day; increase to 5 mg/d daily in 4-5 weeks for 6 - 12 months. Fludarabine 30 mg/m^2 intravenously daily on days -5, -4, -3. Rituximab 375 mg/m2 intravenously on day -13, and 1000 mg/m^2 on days -6, +1 and +8. Thymoglobulin 1.0 mg/kg intravenously over 4 hours (day -2 and -1). On Day 0, donor blood stem cells collected will be transplanted over 30-45 minutes. Bendamustine 130 mg/m2/day by vein daily on day -5, -4, -3 (following Fludarabine). Allopurinol 300 mg by mouth daily beginning at the start of lenalidomide therapy and continuing for 3 months.
Intervention: Rituximab (Drug)
Group 1: Lenalidomide
Chemotherapy, Plus Lenalidomide - Lenalidomide starting dose 5 mg by mouth every other day; increase to 5 mg/d daily in 4-5 weeks for 6 - 12 months. Fludarabine 30 mg/m^2 intravenously daily on days -5, -4, -3. Rituximab 375 mg/m2 intravenously on day -13, and 1000 mg/m^2 on days -6, +1 and +8. Thymoglobulin 1.0 mg/kg intravenously over 4 hours (day -2 and -1). On Day 0, donor blood stem cells collected will be transplanted over 30-45 minutes. Bendamustine 130 mg/m2/day by vein daily on day -5, -4, -3 (following Fludarabine). Allopurinol 300 mg by mouth daily beginning at the start of lenalidomide therapy and continuing for 3 months.
Intervention: Thymoglobulin (Drug)
Group 1: Lenalidomide
Chemotherapy, Plus Lenalidomide - Lenalidomide starting dose 5 mg by mouth every other day; increase to 5 mg/d daily in 4-5 weeks for 6 - 12 months. Fludarabine 30 mg/m^2 intravenously daily on days -5, -4, -3. Rituximab 375 mg/m2 intravenously on day -13, and 1000 mg/m^2 on days -6, +1 and +8. Thymoglobulin 1.0 mg/kg intravenously over 4 hours (day -2 and -1). On Day 0, donor blood stem cells collected will be transplanted over 30-45 minutes. Bendamustine 130 mg/m2/day by vein daily on day -5, -4, -3 (following Fludarabine). Allopurinol 300 mg by mouth daily beginning at the start of lenalidomide therapy and continuing for 3 months.
Intervention: Stem Cell Transplantation (Procedure)
Group 1: Lenalidomide
Chemotherapy, Plus Lenalidomide - Lenalidomide starting dose 5 mg by mouth every other day; increase to 5 mg/d daily in 4-5 weeks for 6 - 12 months. Fludarabine 30 mg/m^2 intravenously daily on days -5, -4, -3. Rituximab 375 mg/m2 intravenously on day -13, and 1000 mg/m^2 on days -6, +1 and +8. Thymoglobulin 1.0 mg/kg intravenously over 4 hours (day -2 and -1). On Day 0, donor blood stem cells collected will be transplanted over 30-45 minutes. Bendamustine 130 mg/m2/day by vein daily on day -5, -4, -3 (following Fludarabine). Allopurinol 300 mg by mouth daily beginning at the start of lenalidomide therapy and continuing for 3 months.
Intervention: Bendamustine (Drug)
Group 1: Lenalidomide
Chemotherapy, Plus Lenalidomide - Lenalidomide starting dose 5 mg by mouth every other day; increase to 5 mg/d daily in 4-5 weeks for 6 - 12 months. Fludarabine 30 mg/m^2 intravenously daily on days -5, -4, -3. Rituximab 375 mg/m2 intravenously on day -13, and 1000 mg/m^2 on days -6, +1 and +8. Thymoglobulin 1.0 mg/kg intravenously over 4 hours (day -2 and -1). On Day 0, donor blood stem cells collected will be transplanted over 30-45 minutes. Bendamustine 130 mg/m2/day by vein daily on day -5, -4, -3 (following Fludarabine). Allopurinol 300 mg by mouth daily beginning at the start of lenalidomide therapy and continuing for 3 months.
Intervention: Allopurinol (Drug)
Group 2: No Lenalidomide
Chemotherapy Treatment, No Lenalidomide - Fludarabine 30 mg/m^2 intravenously daily on days -5, -4, -3. Rituximab 375 mg/m2 intravenously on day -13, and 1000 mg/m^2 on days -6, +1 and +8. Thymoglobulin 1.0 mg/kg intravenously over 4 hours (day -2 and -1). On Day 0, donor blood stem cells collected will be transplanted over 30-45 minutes. Bendamustine 130 mg/m2/day by vein daily on day -5, -4, -3 (following Fludarabine).
Intervention: Fludarabine (Drug)
Group 2: No Lenalidomide
Chemotherapy Treatment, No Lenalidomide - Fludarabine 30 mg/m^2 intravenously daily on days -5, -4, -3. Rituximab 375 mg/m2 intravenously on day -13, and 1000 mg/m^2 on days -6, +1 and +8. Thymoglobulin 1.0 mg/kg intravenously over 4 hours (day -2 and -1). On Day 0, donor blood stem cells collected will be transplanted over 30-45 minutes. Bendamustine 130 mg/m2/day by vein daily on day -5, -4, -3 (following Fludarabine).
Intervention: Rituximab (Drug)
Group 2: No Lenalidomide
Chemotherapy Treatment, No Lenalidomide - Fludarabine 30 mg/m^2 intravenously daily on days -5, -4, -3. Rituximab 375 mg/m2 intravenously on day -13, and 1000 mg/m^2 on days -6, +1 and +8. Thymoglobulin 1.0 mg/kg intravenously over 4 hours (day -2 and -1). On Day 0, donor blood stem cells collected will be transplanted over 30-45 minutes. Bendamustine 130 mg/m2/day by vein daily on day -5, -4, -3 (following Fludarabine).
Intervention: Thymoglobulin (Drug)
Group 2: No Lenalidomide
Chemotherapy Treatment, No Lenalidomide - Fludarabine 30 mg/m^2 intravenously daily on days -5, -4, -3. Rituximab 375 mg/m2 intravenously on day -13, and 1000 mg/m^2 on days -6, +1 and +8. Thymoglobulin 1.0 mg/kg intravenously over 4 hours (day -2 and -1). On Day 0, donor blood stem cells collected will be transplanted over 30-45 minutes. Bendamustine 130 mg/m2/day by vein daily on day -5, -4, -3 (following Fludarabine).
Intervention: Stem Cell Transplantation (Procedure)
Group 2: No Lenalidomide
Chemotherapy Treatment, No Lenalidomide - Fludarabine 30 mg/m^2 intravenously daily on days -5, -4, -3. Rituximab 375 mg/m2 intravenously on day -13, and 1000 mg/m^2 on days -6, +1 and +8. Thymoglobulin 1.0 mg/kg intravenously over 4 hours (day -2 and -1). On Day 0, donor blood stem cells collected will be transplanted over 30-45 minutes. Bendamustine 130 mg/m2/day by vein daily on day -5, -4, -3 (following Fludarabine).
Intervention: Bendamustine (Drug)
Outcomes
Primary Outcomes
Immunomanipulation After Non-myeloablative Stem Cell Transplantation for CLL (Chronic Lymphocytic Leukemia).
Time Frame: Up to 18 months after allotransplant.
To compare the need for immunomanipulation within 18 months after non-myeloablative allogeneic transplantation for CLL between the two combination therapies with or without lenalidomide maintenance. For this purpose, "immunomanipulation" is defined as any one of the following events: 1) Cessation of administering tacrolimus treatment with in the first 6 months after allotransplant due to persistent disease or progression. 2) Boost of donor lymphocytic infusion (DLI) administered anytime between 3 and 18 months after allotransplant.
Secondary Outcomes
- Percentage of Participants With GVHD (Graft Versus Host Disease)(Up to 6 months after allotransplant)