Donor Bone Marrow Transplant in Treating Patients With Leukemia, Lymphoma, or Nonmalignant Hematologic Disorders

Study Overview
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Brief Summary
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RATIONALE: Giving chemotherapy and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from a related or unrelated donor, that closely matches the patient's blood, are infused into the patient they may help the patient's bone marrow to make stem cells, red blood cells, white blood cells, and platelets. PURPOSE: This phase II trial is studying how well donor bone marrow transplant works in treating patients with leukemia, lymphoma, or nonmalignant hematologic disorders.

Detailed Description
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OBJECTIVES: Determine the survival of allogeneic bone marrow transplantation using closely matched related and unrelated donors in patients with malignant or nonmalignant hematological disorders. Determine the incidence and severity of acute and chronic graft versus host disease with this treatment regimen in these patients. Determine the relapse rates with this treatment regimen in those patients with malignant disorders. Determine the incidence and severity of infectious complications associated with this treatment regimen in these patients. OUTLINE: Patients receive cyclophosphamide IV over 1 hour on days -6 and -5, total body radiotherapy on days -3 through 0, and allogeneic bone marrow transplantation on day 0. Patients with acute lymphocytic leukemia (ALL) receive intrathecal methotrexate at the beginning of the study. If CNS involvement is documented, patients receive a second dose of methotrexate 48 hours later followed by oral leucovorin calcium every 6 hours for 4 doses. Patients with ALL and/or CNS involvement receive intrathecal methotrexate every other week for 12 weeks after transplant. Patients with prior CNS involvement receive radiotherapy for 2.5 weeks prior to transplant. Patients with ALL receive total body radiotherapy for 5 consecutive days prior to transplant. Patients are followed once a week for 3 months, and then monthly for 1 year. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study over 6 years.

Official Title
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Allogeneic Bone Marrow Transplantation Using Closely Matched Related and Unrelated Donors

Conditions
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Chronic Myeloproliferative Disorders, Leukemia, Multiple Myeloma and Malignant Plasma Cell Neoplasms, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

Intervention / Treatment
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* Drug: cyclophosphamide
* Radiation: TBI


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed diagnosis of one of the following: Acute lymphocytic leukemia (ALL): Complete remission (CR) 1 - high risk defined as overt CNS involvement or poor cytogenetics (additions, deletions, translocations, or multiple abnormalities) CR2 Induction failures Relapse - patients with at least 10% marrow blasts undergo at least one reinduction attempt Acute myelogenous leukemia (AML): CR1 - high risk defined as poor cytogenetics (deletions, additions, multiple abnormalities) CR2 Induction failures Relapse - patients with at least 10% marrow blasts undergo at least one reinduction attempt Chronic myelogenous leukemia (CML): Chronic phase (CP) 1 Accelerated phase/CP2 - patients in blast phase must undergo treatment and achieve a second chronic phase prior to transplant Chronic lymphocytic leukemia (CLL): Relapse - any stage; must have received no more than 3 prior regimens Multiple myeloma: At diagnosis - primary refractory Relapse (no more than 2) - sensitive disease Plasma cell leukemia Inability to achieve a complete remission after autologous transplant (no older than 40) Myelodysplasia - all subtypes Myeloproliferative disorders - patients with poor response to medical therapy or cytogenetic abnormalities Severe aplastic anemia (SAA): Very SAA - at diagnosis SAA - induction therapy Donors must be a phenotypic (6 out of 6) match or a one antigen (A or B) mismatch PATIENT CHARACTERISTICS: Age: 15 to 50 Performance status: Karnofsky 80-100% Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no greater than 2.0 mg/dL SGOT and SGPT no greater than 3 times normal PT/PTT normal Renal: Creatinine no greater than 2.0 mg/dL Creatinine clearance at least 60 mL/min Cardiovascular: Left ventricular ejection fraction at least 45% No myocardial infarction within past 6 months No uncontrolled arrhythmias Pulmonary: FEV1 at least 50% DLCO at least 50% predicted Other: No active serious infection HIV negative Not pregnant or nursing No uncontrolled diabetes mellitus or thyroid disease PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Chemotherapy: See Disease Characteristics Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 50 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cy/TBI<br>cyclophosphamide and total body irradiation (TBI) | Drug: cyclophosphamide<br>* Cyclophosphamide is administered at a dose of 60 mg/kg on each of two successive days (Days -6 and -5)<br>Radiation: TBI<br>* FTBI is performed on day -3 through day 0 The total dose of radiation is 1,320 cGy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| event free survival (EFS) | EFS determined by the Kaplan-Meier product limit method | five year post transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of graft versus host disease | incidence and severity of acute and chronic GVHD | five years post transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent childhood acute lymphoblastic leukemia, refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, recurrent childhood acute myeloid leukemia, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, refractory chronic lymphocytic leukemia, chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, adult acute myeloid leukemia in remission, adult acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, childhood acute lymphoblastic leukemia in remission, polycythemia vera, primary myelofibrosis, essential thrombocythemia, refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, refractory cytopenia with multilineage dysplasia, chronic eosinophilic leukemia, chronic neutrophilic leukemia, atypical chronic myeloid leukemia, BCR-ABL1 negative, myelodysplastic/myeloproliferative neoplasm, unclassifiable, adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(15;17)(q22;q12), childhood myelodysplastic syndromes