High-Dose Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: This phase II trial is studying how well giving busulfan, cyclophosphamide, and filgrastim together with peripheral stem cell transplantation from a sibling donor works in treating patients with hematologic cancer.

Detailed Description
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OBJECTIVES: Determine the safety and feasibility of using allogeneic peripheral blood progenitor cell infusions obtained from normal histocompatible sibling donors for reconstituting bone marrow and immunologic function when given after high-dose busulfan/cyclophosphamide in patients with a hematologic malignancy. Determine the efficacy of this treatment in these patients. Determine the ability to mobilize hematopoietic progenitor cells from normal donors given filgrastim (G-CSF) by determining the hematopoietic progenitor cell content of allogeneic peripheral blood progenitor cell collections. Determine the incidence of engraftment failures in these patients. Determine the incidence of severe acute graft-versus-host disease in these patients. OUTLINE: Patients receive high-dose oral busulfan every 6 hours on days -8 to -5, cyclophosphamide IV twice a day on days -4 and -3, and cyclosporine IV over 6 hours on day -1 and then 10 hours on day 0 for 2 doses (allogeneic only). Allogeneic peripheral blood progenitor cells IV are administered on day 0. Filgrastim (G-CSF) is administered subcutaneously twice a day beginning 3 hours after completion of cell infusion and continuing until blood counts recover. Patients are followed every month for 2 months, every 3 months for 6 months, and then every 6 months until disease progression. PROJECTED ACCRUAL: A total of 40 patients will be accrued over a 15 month period.

Official Title
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Allogeneic Peripheral Blood Progenitor Cell Transplantation Using Histocompatible Sibling-Matched Donor Cells After High-Dose Busulfan/Cyclophosphamide as Therapy for Hematologic Malignancies

Conditions
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Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

Intervention / Treatment
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* Biological: filgrastim
* Drug: busulfan
* Drug: cyclophosphamide
* Drug: cyclosporine
* Procedure: bone marrow ablation with stem cell support
* Procedure: peripheral blood stem cell transplantation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically diagnosed: Acute myeloid leukemia in first, second, or third complete remission or first or second early relapse Acute lymphoblastic leukemia in first, second, or third complete remission or first or second early relapse Hodgkin's lymphoma in second or third remission or first, second, or third relapse, or refractory Non-Hodgkin's lymphoma in second or third remission or first, second, or third relapse, or refractory Multiple myeloma and plasma cell leukemia in second or third remission or first, second, or third relapse, or refractory Myelodysplastic syndrome deemed suitable for allogeneic bone marrow transplantation No symptoms or signs of CNS involvement and CNS is disease free on lumbar puncture and brain CT scan No active meningeal cancer PATIENT CHARACTERISTICS: Age: 4 to 55 (4 to 60 if donor is identical twin) Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: SGOT/SGPT less than 3 times normal Bilirubin less than 2.0 mg/dL Renal: Creatinine less than 2.1 mg/dL Creatinine clearance at least 60 mL/min (no greater than 1.5 times normal for children under 40 kg) Cardiovascular: No uncontrolled hypertension No uncontrolled congestive heart failure No active angina pectoris requiring nitrates At least 6 months since prior myocardial infarction No major ventricular arrhythmia Left ventricular ejection fraction at least 45% on MUGA Pulmonary: No severe or symptomatic restrictive or obstructive lung disease FEV_1 greater than 50% of predicted DLCO greater than 50% of predicted Neurologic: No severe central or peripheral neurologic abnormality Other: Must have HLA-A,B,C,D/DR identical sibling age 4 to 65, in good health No insulin-dependent diabetes mellitus No major thyroid or major adrenal dysfunction No active infection No other active malignancy Not pregnant HIV negative HTLV-I and HTLV-II negative PRIOR CONCURRENT THERAPY: Biologic therapy: No excessive anthracycline exposure, unless endomyocardial biopsy shows less than grade 2 drug effect and cardiac scan shows at least 50% ejection fraction At least 1 year since prior autologous bone marrow or peripheral blood progenitor cell transplant or allogeneic bone marrow transplant Chemotherapy: At least 3 weeks since prior chemotherapy No prior excessive carmustine and bleomycin Endocrine therapy: Not specified Radiotherapy: At least 3 weeks since prior radiotherapy Surgery: Not specified Other: No concurrent nitroglycerin for angina pectoris No concurrent anti-arrhythmic drugs for major ventricular dysrhythmias

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 55 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

| Intervention/Treatment |
| --- |
|Biological: filgrastim|Filgrastim (G-CSF) is administered subcutaneously twice a day beginning 3 hours after completion of cell infusion and continuing until blood counts recover.|
|Drug: busulfan|high-dose oral busulfan every 6 hours on days -8 to -5|
|Drug: cyclophosphamide|cyclophosphamide IV twice a day on days -4 and -3|
|Drug: cyclosporine|cyclosporine IV over 6 hours on day -1 and then 10 hours on day 0 for 2 doses (allogeneic only)|
|Procedure: bone marrow ablation with stem cell support|nan|
|Procedure: peripheral blood stem cell transplantation|Allogeneic peripheral blood progenitor cells IV are administered on day 0.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematopoietic reconstitution measured daily during transplant |  | at months 2, 4, 7, and 10, and then every 6 months until disease progression | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent childhood acute lymphoblastic leukemia, recurrent adult Hodgkin lymphoma, refractory multiple myeloma, recurrent childhood lymphoblastic lymphoma, recurrent childhood acute myeloid leukemia, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic 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, recurrent/refractory childhood Hodgkin lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, recurrent childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma, recurrent mantle cell lymphoma, atypical chronic myeloid leukemia, myelodysplastic/myeloproliferative disease, unclassifiable, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, 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