Stem Cell Transplant in Treating Patients With Hematological Cancer or Other Disorders

Study Overview
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Brief Summary
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RATIONALE: Giving chemotherapy, such as fludarabine, busulfan, and cyclophosphamide, together with antithymocyte globulin before a donor stem cell transplant helps stop the growth of cancer and abnormal cells. Giving chemotherapy before or after transplant also stops 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 and 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. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. PURPOSE: This phase II trial is studying how well stem cell transplant works in treating patients with hematological cancer or other disorders.

Detailed Description
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OBJECTIVES: Primary Evaluate the incidence of graft acceptance in patients with hematological disorders treated with combined immunosuppression before and after HLA-haploidentical hematopoietic stem cell transplantation. Secondary Evaluate efficacy of this regimen in these patients. Evaluate toxicity of this regimen in these patients. Assess survival of patients treated with this regimen. OUTLINE: This is a multicenter study. Reduced-intensity conditioning: Patients receive fludarabine phosphate IV on days -6 to -1, busulfan IV on days -6 to -5, and anti-thymocyte globulin IV on days -4 to -1. Transplantation: Patients undergo transplantation of donor hematopoietic stem cells on day 0. Patients also receive cyclophosphamide IV on day 3 and filgrastim (G-CSF) beginning on day 4 and continuing until blood counts recover. Immunosuppression: Patients receive cyclosporine IV beginning on day -2 and continuing for 6 months and mycophenolate mofetil 4 times a day on days 4-84.

Official Title
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Allograft of Hematopoietic Stem Cells With Reduced-intensity Conditioning From a HLA-haploidentical Family Donor: Phase II Study of Combined Immunosuppression Before and After Transplantation

Conditions
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Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Precancerous Condition

Intervention / Treatment
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* Biological: anti-thymocyte globulin
* Drug: busulfan
* Drug: cyclophosphamide
* Drug: cyclosporine
* Drug: fludarabine phosphate
* Drug: mycophenolate mofetil
* Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of any of the following hematological cancers with a poor prognosis: Acute myeloid leukemia meeting 1 of the following criteria: Third complete remission (CR3) or beyond CR2 after an early bone marrow relapse (< 24 months) Refractory disease after ≥ 2 chemotherapy courses of induction therapy Acute lymphoblastic leukemia meeting 1 of the following criteria: CR3 after ≥ 1 bone marrow relapse CR2 after early bone marrow relapse (currently or within 6 months after stopping maintenance therapy) Chronic myelogenous leukemia meeting the following criteria: Accelerated phase Second chronic phase No other treatment options Multiple myeloma meeting the following criteria: Failed conventional therapy (including autologous hematopoietic stem cell transplantation) No other treatment alternatives Chronic lymphocytic leukemia meeting the following criteria: Failed conventional therapy No other treatment alternatives Hodgkin lymphoma meeting the following criteria: Failed conventional therapy No other treatment alternatives Non-Hodgkin lymphoma meeting the following criteria: Failed conventional therapy No other treatment alternatives Not eligible for standard myeloablative allograft due to increased toxicity Healthy related donor available and meeting the following criteria: Brother, sister, father, mother, cousin, uncle, or aunt At least an identical HLA haplotype Identical genotype on 1 haplotype (in terms of HLA-A, B, C, and DR) Different on ≤ 4 alleles on the other haplotype No HLA-identical intra- or extra-familial donor cord blood available within the next 3 months PATIENT CHARACTERISTICS: Karnofsky performance status 70-100% Not pregnant or nursing Fertile patients must use effective contraception No contraindication to allogeneic transplantation, including any of the following: Cardiac systolic ejection fraction < 40% DLCO level limiting use of fludarabine Creatinine clearance < 30 mL/min Transaminases and/or bilirubin > 3 times upper limit of normal (unless due to Gilbert disease or cancer) HIV seropositivity Human T-cell lymphotrophic virus type 1 seropositivity Uncontrolled bacterial, viral, or fungal infection No contraindication to any of the study drugs No prior or concurrent psychiatric illness No other cancer in the past 5 years except for basal cell skin cancer or carcinoma in situ of the cervix No concurrent serious, uncontrolled condition No patients deprived of liberty or subject to legal protection PRIOR CONCURRENT THERAPY: No participation in a study of allografts in the past month

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: anti-thymocyte globulin|nan|
|Drug: busulfan|nan|
|Drug: cyclophosphamide|nan|
|Drug: cyclosporine|nan|
|Drug: fludarabine phosphate|nan|
|Drug: mycophenolate mofetil|nan|
|Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of graft acceptance |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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graft versus host disease, adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), recurrent adult acute myeloid leukemia, adult acute lymphoblastic leukemia in remission, recurrent adult acute lymphoblastic leukemia, accelerated phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, refractory multiple myeloma, relapsing chronic myelogenous leukemia, recurrent adult Hodgkin lymphoma, adult nasal type extranodal NK/T-cell lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult grade III lymphomatoid granulomatosis, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult T-cell leukemia/lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent grade I lymphomatoid granulomatosis, recurrent grade II lymphomatoid granulomatosis, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, splenic marginal zone lymphoma, refractory chronic lymphocytic leukemia