Total-Body Irradiation, Cyclophosphamide, and Stem Cell Transplantation in Treating Patients With Hematologic Cancer

Study Overview
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Brief Summary
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RATIONALE: Adjusting the dose of drugs used in chemotherapy such as cyclophosphamide may decrease side effects while stopping cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill cancer cells. PURPOSE: Phase I trial to study the effect on the body of dose-adjusted cyclophosphamide combined with total-body irradiation and donor stem cell transplantation in treating patients who have hematologic cancer.

Detailed Description
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OBJECTIVES: Determine a safe and reproducible method of adjusting the dose of cyclophosphamide based on its metabolism when given in combination with total body irradiation and hematopoietic stem cell transplantation in patients with hematologic malignancy. OUTLINE: Preparative regimen: Patients undergo total body irradiation twice daily on days -6 to -4. Patients then receive dose-adjusted (based on metabolism) cyclophosphamide IV over 1 hour on days -3 and -2. Hematopoietic stem cell (HSC) infusion: Patients undergo allogeneic HSC transplantation on day 0. Patients receive graft-versus-host disease prophylaxis, CNS prophylaxis, and testicular irradiation as per institutional standard practices. Patients are followed daily until day 80 after transplantation and then regularly thereafter for survival. PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Official Title
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A Phase I Trial Of Total Body Irradiation, Cyclophosphamide Dose-Adjustment Based On Its Metabolism, And Hematopoietic Stem Cell Transplantation For Patients With Hematological Malignancy

Conditions
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Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

Intervention / Treatment
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* Drug: cyclophosphamide
* Procedure: allogeneic bone marrow transplantation
* Procedure: peripheral blood stem cell transplantation
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of hematological malignancy, including any of the following: Chronic myeloid leukemia Acute myeloid leukemia Acute lymphocytic leukemia Myelodysplastic syndromes Lymphoma Unlikely to respond to conventional treatment and would benefit from hematopoietic stem cell transplantation No bulky tumor mass requiring additional involved field radiotherapy No large body burden of tumor cells requiring cytoreductive chemotherapy before total body irraditation and cyclophosphamide Undergoing conditioning for transplantation at the University of Washington Medical Center Availability of 1 of the following types of allogeneic donors: HLA-identical family members Unrelated donors Allele match (match grade 1) One allele mismatch for A, B, C, DRB1 or DQB1 (match grades 2.1 or 2.2) PATIENT CHARACTERISTICS: Age 18 to 65 Performance status Not specified Life expectancy Not severely limited by diseases other than malignancy Not moribund Hematopoietic Not specified Hepatic Bilirubin no greater than 1.2 mg/dL No cirrhosis No hepatic fibrosis with bridging Renal Creatinine no greater than 1.2 mg/dL Cardiovascular No coronary artery disease No congestive heart failure requiring therapy Pulmonary Oxygen saturation at least 93% (on room air) Other Not pregnant or nursing Fertile patients must use effective contraception HIV negative No concurrent infection requiring systemic antibiotic or antifungal therapy PRIOR CONCURRENT THERAPY: Biologic therapy No prior hematopoietic stem cell transplantation Chemotherapy See Disease Characteristics Endocrine therapy Not specified Radiotherapy See Disease Characteristics No prior radiotherapy to the liver or adjacent organs Surgery Not specified Other No concurrent aspirin or nonsteroidal anti-inflammatory medications such as ibuprofen (e.g., Motrin® or Advil®) No other concurrent phase I study enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cyclophosphamide|nan|
|Procedure: allogeneic bone marrow transplantation|nan|
|Procedure: peripheral blood stem cell transplantation|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult Burkitt lymphoma, recurrent adult Hodgkin lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, noncontiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, noncontiguous stage II adult lymphoblastic lymphoma, noncontiguous stage II grade 3 follicular lymphoma, noncontiguous stage II mantle cell lymphoma, stage III adult lymphoblastic lymphoma, stage IV adult lymphoblastic lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, recurrent adult acute myeloid leukemia, untreated adult acute myeloid leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, meningeal chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, noncontiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, recurrent mycosis fungoides/Sezary syndrome, secondary acute myeloid leukemia, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III grade 3 follicular lymphoma, stage III adult diffuse large cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage III mantle cell lymphoma, stage IV grade 3 follicular lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV mantle cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, recurrent adult acute lymphoblastic leukemia, untreated adult acute lymphoblastic leukemia, atypical chronic myeloid leukemia, myelodysplastic/myeloproliferative disease, unclassifiable, noncontiguous stage II small lymphocytic lymphoma, noncontiguous stage II marginal zone lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage III marginal zone lymphoma, stage IV small lymphocytic lymphoma, stage IV marginal zone 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)