Donor Stem Cell Transplant in Treating Patients With High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Status: Recruiting
Phase: Phase 2
Diagnosis: Leukemia/MDS, Hematopoietic Stem Cell Transplant
NCT ID: NCT01027000
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 10-245
RATIONALE: Giving low doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as rituximab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus, sirolimus, and methotrexate after the transplant may stop this from happening. PURPOSE: This phase II trial is studying how well donor stem cell transplant works in treating patients with high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma.
Conducting Institutions:
Dana-Farber Cancer Institute, Massachusetts General Hospital
Overall PI:
Edwin Alyea, MD,
Dana-Farber Cancer Institute
Site-responsible Investigators:
Yi-Bin Chen, MD,
Massachusetts General Hospital
Contacts:
Dana-Farber Cancer Institute:
Ilene Galinsky, 617-632-3902,
igalinsky@partners.org
Massachusetts General Hospital:
Cancer Trials Call Center, 877-789-6100
Eligibility Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of B-cell chronic lymphocytic leukemia or B-cell small lymphocytic lymphoma
according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008
criteria
- Meets 1 of the following criteria:
- Early disease cohort:
- Meets ≥ 1 of the following criteria:
- FISH showing deletion 17p in ≥ 20% of cells (either at diagnosis or
any time before study entry) either alone or in combination with other
cytogenetic abnormalities
- FISH showing deletion 11q in ≥ 20% of cells (either at diagnosis or
any time before study entry) either alone or in combination with other
cytogenetic abnormalities, unless the patient has achieved a complete
remission, according to IWCLL 2008 criteria which includes CT scan,
bone marrow morphology, and flow cytometry
- Failed to achieve a partial response to initial purine analog-based
combination therapy (e.g., fludarabine phosphate and rituximab;
fludarabine phosphate, cyclophosphamide, and rituximab; pentostatin,
cyclophosphamide, and rituximab; or alemtuzumab), but has no disease
progression (may receive a second therapy to improve response before
transplant)
- Received ≥ 2 courses of induction therapy with combination therapy that is
purine analog-based (e.g., fludarabine phosphate and rituximab; fludarabine
phosphate, cyclophosphamide, and rituximab; or pentostatin,
cyclophosphamide, and rituximab) (may not receive > 2 different regimens
before proceeding to transplantation)
- Stable disease or better after most recent therapy (i.e., no prior
progression), according to the revised IWCLL 2008 criteria
- Nodes ≤ 5 cm
- Advanced disease cohort:
- Meets ≥ 1 of the following criteria:
- First disease progression < 24 months after completing a purine
analog-based therapy (e.g., fludarabine phosphate and rituximab;
fludarabine phosphate, cyclophosphamide, and rituximab; pentostatin,
cyclophosphamide, and rituximab; or alemtuzumab) (this includes
progression on initial therapy)
- Second or subsequent progression
- Stable disease or better after most recent chemotherapy, according to the
revised IWCLL 2008 criteria
- Nodes < 5 cm
- Has an HLA-matched related or unrelated donor available
- 6/6 HLA-matched related donor by low-resolution typing at HLA A, B, C, and DR
- 8/8 HLA-matched unrelated donor by molecular typing at both HLA class I and
class II (A, B, C, and DR loci)
- No syngeneic donors
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Serum creatinine < 2 mg/dL
- Calculated creatinine clearance ≥ 40 mL/min
- AST < 3 times upper limit of normal
- Total bilirubin < 2 mg/dL (except for patients with Gilbert syndrome)
- DLCO ≥ 40% predicted
- LVEF ≥ 30% by ECHO or MUGA
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- Hepatitis B surface antigen negative
- Anti-hepatitis B core antigen negative
- Hepatitis C antibody negative
- No uncontrolled diabetes mellitus or active uncontrolled serious infections
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 4 weeks since prior cytotoxic chemotherapy or alemtuzumab