Reduced-Intensity Busulfan and Fludarabine With or Without Antithymocyte Globulin Followed by Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Other Disease

• Status: Completed
• Trial end date: 2012-05-23
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Giving low doses of chemotherapy, such as busulfan and fludarabine, before a donor stem cell transplant helps stop the growth of cancer and abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer or abnormal cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Immunosuppressive therapy may improve bone marrow function and may be an effective treatment for hematologic cancer or other disease.

PURPOSE: This clinical trial is studying the side effects and how well giving busulfan and fludarabine with or without antithymocyte globulin followed by donor stem cell transplant works in treating patients with hematologic cancer or other disease.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Antilymphocyte Serum; Busulfan; Fludarabine; Fludarabine phosphate; Methotrexate; Sargramostim; Tacrolimus

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of 1 of the following:

• Chronic lymphocytic leukemia (CLL), meeting the following criteria:

• Absolute lymphocyte count > 5,000/mm³

• Lymphocytes must appear morphologically mature with < 55% prolymphocytes

• Lymphocyte phenotype with expression of CD19 and cluster of differentiation 5 (CD5)

• Prolymphocytic leukemia (PLL), meeting the following criteria:

• Absolute lymphocyte count > 5,000/mm³

• More than 55% prolymphocytes

• Morphologically diagnosed

• Chronic myelogenous leukemia (CML), meeting the following criteria:

• Diagnosis of CML or similar myeloproliferative disorders based on t(9;22) or related t(9;12) cytogenetic abnormalities AND characterized by elevated white blood cell (WBC) counts in peripheral blood or bone marrow

• In first chronic phase CML and a candidate for treatment with reduced-dose busulfan

• Patients with other cytogenetic abnormalities, such as t(9;12), that are associated with an aggressive clinical course are eligible

• Non-Hodgkin's lymphoma (NHL), meeting the following criteria:

• Any World Health Organization (WHO) class histologic subtype allowed

• Core biopsies are acceptable provided they contain adequate tissue for primary diagnosis and immunophenotyping

• Bone marrow biopsies as sole means of diagnosis are not allowed for follicular lymphoma

• Hodgkin's lymphoma, meeting the following criteria:

• Any WHO class histologic subtype allowed

• Core biopsies are acceptable provided they contain adequate tissue for primary diagnosis and immunophenotyping

• Multiple myeloma, meeting the following criteria:

• Active disease requiring treatment (Durie-Salmon stages I, II, or III)

• Acute myeloid leukemia with documented control, defined as < 10% bone marrow blasts and no circulating blasts

• Acute lymphoblastic leukemia, meeting the following criteria:

• In early first relapse or beyond OR in first complete remission and has 1 of the following high-risk features:

• t(9;22) or t(4;11)

• WBC count > 30,000/mm³ at presentation

• Non-T-cell phenotype

• More than 30 years of age

• Agnogenic myeloid metaplasia/myelofibrosis

• Patients who are transfusion dependent or who have evolving myelodysplastic or leukemic features or high-risk cytogenetic abnormalities are eligible

• Myelodysplastic syndromes (MDS) as defined by WHO criteria

• Meets 1 of the following criteria:

• Over 55 years of age

• Ineligible for busulfan-based therapy based on diminished organ function or poor performance status

• Indolent and chemotherapy-responsive CLL, low-grade NHL, small lymphocytic lymphoma, or PLL

• Patients who have undergone prior autologous stem cell transplantation are preferentially enrolled on clinical trial CALGB-100002, if available and patient is eligible

• HLA-matched or mismatched related donor or HLA-matched unrelated donor available

• HLA-identical sibling (6/6 or 9/10) (minimal serologic typing required for class I [A, B]; molecular typing required for class II (DRB1))

• 9/10 matched unrelated donor (MUD) (molecular analysis at HLA A, B, C, DRB1, and DQB1 by high resolution typing required)

• 5/6 MUD (molecular analysis at HLA A, B, and DRB1 required)

• No syngeneic donors

PATIENT CHARACTERISTICS:

• Creatinine clearance ≥ 40 mL/min

• Bilirubin ≤ 3 times upper limit of normal (ULN)

• aspartate aminotransferase (AST) ≤ 3 times ULN

• Diffusing capacity of the lungs for carbon monoxide (DLCO) > 40% with no symptomatic pulmonary disease

• Left ventricular ejection fraction (LVEF) ≥ 30% by multigated acquisition scan (MUGA)

• No uncontrolled diabetes mellitus or active serious infection

• No known hypersensitivity to Escherichia coli-derived products

• No HIV infection

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• More than 4 weeks since prior chemotherapy, radiotherapy (except prophylactic cranial x-ray therapy), or surgery