S0125, Chemotherapy, Total-Body Irradiation, and Peripheral Stem Cell Transplantation in Treating Older Patients With Acute Myeloid Leukemia

Study Overview
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Brief Summary
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RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Cyclosporine and mycophenolate mofetil may prevent this from happening. PURPOSE: Phase II trial to study the effectiveness of chemotherapy and total-body irradiation followed by donor peripheral stem cell transplantation, cyclosporine, and mycophenolate mofetil in treating older patients who have acute myeloid leukemia.

Detailed Description
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Primary objective: Determine whether allogeneic peripheral blood stem cell transplantation with pre-conditioning low dose total body irradiation and fludarabine followed by cyclosporine and mycophenolate mofetil, when given to elderly patients with acute myeloid leukemia in first complete remission, is sufficiently efficacious (in terms of survival 1 year after transplantation) to warrant a phase III investigation. Secondary objective: Determine the frequency and severity of toxic effects of this regimen in these patients. Other objectives as funding permits: Determine whether chimerism patterns in bone marrow and blood after transplantation are associated with relapse and/or graft-versus-host disease (GVHD) in these patients. Determine whether cytogenic, immunophenotypic, and molecular biologic features detected in pre- and post-transplantation specimens are related to transplant outcomes and risk of relapse in these patients. OUTLINE: This is an open-label study. Conditioning regimen: Patients receive fludarabine IV over 1 hour on days -4 to -2. Patients also undergo total body irradiation on day 0. Peripheral blood stem cell infusion (PBSC): Patients receive unmodified filgrastim transplantation (G-CSF)-mobilized donor PBSC on day 0. Post-transplantation immunosuppression: Patients receive oral cyclosporine on days -3 to 35 followed by a taper until day 180. Patients also receive oral mycophenolate mofetil on day 0 to 27 without tapering. Donor lymphocyte infusions (DLI): Patients with relapsed disease receive DLI IV over 30 minutes for up to 2 infusions. Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years. PROJECTED ACCRUAL: A total of 25-51 patients will be accrued for this study.

Official Title
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S0125, A Phase II Study Of Chimerism-Mediated Immunotherapy (CMI) Using Nonmyeloablative Allogeneic Peripheral Blood Stem Cell Transplantation In Older Patients With Acute Myeloid Leukemia (AML) In First Complete Remission (A BMT Study)

Conditions
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Leukemia

Intervention / Treatment
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* Biological: therapeutic allogeneic lymphocytes
* Drug: cyclosporine
* Drug: fludarabine
* Drug: mycophenolate mofetil
* Procedure: peripheral blood stem cell transplantation
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Morphologically confirmed acute myeloid leukemia (AML) (within 180 days of diagnosis) OR Secondary AML (secondary to myelodysplastic syndromes (MDS) or to prior leukemogenic therapy) Must have A1 marrow, B1 blood, and C1 extramedullary disease status Must have received prior remission induction chemotherapy Must have a genotypically HLA-identical sibling donor available that is not a monozygotic identical twin No M3 AML or blastic transformation of chronic myelogenous leukemia If history of CNS leukemia, no leukemia cells in CNS by lumbar puncture within past 7 days Must be concurrently enrolled on protocols SWOG-9007 and SWOG-S9910 PATIENT CHARACTERISTICS: Age 55 to 69 Performance status Zubrod 0-2 Life expectancy Not specified Hematopoietic See Disease Characteristics Hepatic Not specified Renal Not specified Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No other malignancy within the past 2 years except for the following: Adequately treated basal cell or squamous cell skin cancer Carcinoma in situ of the cervix Adequately treated stage I or II cancer in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy No prior allogeneic hematopoietic stem cell transplantation Chemotherapy See Disease Characteristics Prior consolidation therapy allowed Endocrine therapy Not specified Radiotherapy Not specified Surgery Prior organ transplantation allowed provided not concurrently receiving immunosuppressive therapy

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 69 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 |
| --- | --- |
| Experimental: treatment<br>patient conditioning - fludarabine 30 mg/m2 IV over 1 hour Days -4, -3, -2; TBI 6-7 cGy/min Day 0 post-transplant immunosuppression - cyclosporine 6.25 mg/kg bid PO D -3 to +180 (begin taper on D+35); mycophenolate mofetil 15mg/kg bid PO D0 to +27 | Biological: therapeutic allogeneic lymphocytes<br> <br> Drug: cyclosporine<br> <br> Drug: fludarabine<br> <br> Drug: mycophenolate mofetil<br> <br> * Other names: MMF;Procedure: peripheral blood stem cell transplantation<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | measured from date of registration to study until death from any cause with patients still alive censored at date of last contact | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious Adverse Events | Twice a week for the first two months, one time a week during month 3, one time every two weeks for months 4-9. | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult acute myeloid leukemia in remission, 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