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

SWOG Cancer Research Network

Status and phase: Terminated; Phase 2

Conditions: Leukemia

Treatments: Radiation: radiation therapy; Drug: fludarabine; Drug: cyclosporine; Procedure: peripheral blood stem cell transplantation; Biological: therapeutic allogeneic lymphocytes; Drug: mycophenolate mofetil

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00053014

S0125 (Other Identifier)

U10CA032102 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 5 patients

Sex: All

Ages: 55 to 69 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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5 participants in 1 patient group

treatment

Experimental group

Description:

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

Treatment:

Drug: mycophenolate mofetil

Procedure: peripheral blood stem cell transplantation

Biological: therapeutic allogeneic lymphocytes

Radiation: radiation therapy

Drug: fludarabine

Drug: cyclosporine