Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic/Myeloproliferative Diseases, Myelodysplastic Syndromes
Conditions
Keywords
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
Brief summary
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
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.
Interventions
BIOLOGICALfilgrastim
Filgrastim (G-CSF) is administered subcutaneously twice a day beginning 3 hours after completion of cell infusion and continuing until blood counts recover.
DRUGbusulfan
high-dose oral busulfan every 6 hours on days -8 to -5
DRUGcyclophosphamide
cyclophosphamide IV twice a day on days -4 and -3
DRUGcyclosporine
cyclosporine IV over 6 hours on day -1 and then 10 hours on day 0 for 2 doses (allogeneic only)
PROCEDUREbone marrow ablation with stem cell support
PROCEDUREperipheral blood stem cell transplantation
Allogeneic peripheral blood progenitor cells IV are administered on day 0.
Sponsors
National Cancer Institute (NCI)
Case Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Hematopoietic reconstitution measured daily during transplant | at months 2, 4, 7, and 10, and then every 6 months until disease progression |
Countries
United States
Outcome results
None listed