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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Leukemia
• Intervention / Treatment: Radiation: radiation therapy; Biological: therapeutic allogeneic lymphocytes; Procedure: peripheral blood stem cell transplantation; Drug: cyclosporine; Drug: mycophenolate mofetil; Drug: fludarabine

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Good Samaritan Medical Center
    • Tucson, Arizona, United States, 85723
      • Veterans Affairs Medical Center - Tucson
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center at University of Arizona Health Sciences Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
    • Little Rock, Arkansas, United States, 72205
      • Veterans Affairs Medical Center - Little Rock
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center
    • La Jolla, California, United States, 92037-1027
      • Scripps Cancer Center at Scripps Clinic
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Los Angeles, California, United States, 90095-1678
      • Jonsson Comprehensive Cancer Center at UCLA
    • Martinez, California, United States, 94553
      • Veterans Affairs Outpatient Clinic - Martinez
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
    • Sacramento, California, United States, 95816
      • Sutter Cancer Center
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • Stanford, California, United States, 94305-5408
      • Stanford Cancer Center at Stanford University Medical Center
    • Travis Air Force Base, California, United States, 94535
      • General Robert Huyser Cancer Center at David Grant Medical Center
    • Walnut Creek, California, United States, 94598
      • John Muir/Mt. Diablo Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80010
      • University of Colorado Cancer Center at University of Colorado Health Sciences Center
    • Denver, Colorado, United States, 80220
      • Veterans Affairs Medical Center - Denver
  • Florida
    • Tampa, Florida, United States, 33612
      • Veterans Affairs Medical Center - Tampa (Haley)
  • Georgia
    • Atlanta, Georgia, United States, 30342-1701
      • CCOP - Atlanta Regional
    • Decatur, Georgia, United States, 30033
      • Charles B. Eberhart Cancer Center at DeKalb Medical Center
    • Fort Gordon, Georgia, United States, 30905-5650
      • Dwight David Eisenhower Army Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Cancer Research Center of Hawaii
    • Honolulu, Hawaii, United States, 96813
      • MBCCOP - Hawaii
  • Idaho
    • Boise, Idaho, United States, 83712
      • Mountain States Tumor Institute - Boise
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Veterans Affairs Medical Center - Chicago Westside Hospital
    • Hines, Illinois, United States, 60141
      • Veterans Affairs Medical Center - Hines
    • Maywood, Illinois, United States, 60153-5500
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • Indiana Blood and Marrow Transplantation
  • Kansas
    • Kansas City, Kansas, United States, 66160-7353
      • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67218
      • Veterans Affairs Medical Center - Wichita
  • Kentucky
    • Lexington, Kentucky, United States, 40502-2236
      • Veterans Affairs Medical Center - Lexington
    • Lexington, Kentucky, United States, 40536-0084
      • Markey Cancer Center at University of Kentucky Chandler Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Veterans Affairs Medical Center - New Orleans
    • New Orleans, Louisiana, United States, 70112
      • MBCCOP - LSU Health Sciences Center
    • New Orleans, Louisiana, United States, 70115
      • New Orleans Cancer Institute at Memorial Medical Center
    • New Orleans, Louisiana, United States, 70112
      • Tulane Cancer Center at Tulane University Hospital and Clinic
    • Shreveport, Louisiana, United States, 71130-3932
      • Feist-Weiller Cancer Center at Louisiana State University Health Sciences
    • Shreveport, Louisiana, United States, 71101-4295
      • Veterans Affairs Medical Center - Shreveport
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Boston, Massachusetts, United States, 02118
      • Cancer Research Center at Boston Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0948
      • University of Michigan Comprehensive Cancer Center
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48201-1932
      • Veterans Affairs Medical Center - Detroit
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Health System
    • Southfield, Michigan, United States, 48075
      • Providence Cancer Institute at Providence Hospital - Southfield Campus
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Medical Center
    • Jackson, Mississippi, United States, 39216
      • Veterans Affairs Medical Center - Jackson
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University Cancer Center
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108-5138
      • Veterans Affairs Medical Center - Albuquerque
  • New York
    • Albany, New York, United States, 12208
      • Veterans Affairs Medical Center - Albany
    • New York, New York, United States, 10016
      • NYU Cancer Institute at New York University Medical Center
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center at Columbia University
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45220-2288
      • Veterans Affairs Medical Center - Cincinnati
    • Cleveland, Ohio, United States, 44195-9001
      • Cleveland Clinic Taussig Cancer Center
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
    • Dayton, Ohio, United States, 45428-1002
      • Veterans Affairs Medical Center - Dayton
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Veterans Affairs Medical Center - Oklahoma City
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97225
      • CCOP - Columbia River Oncology Program
    • Portland, Oregon, United States, 97201-3098
      • Cancer Institute at Oregon Health and Science University
  • South Carolina
    • Charleston, South Carolina, United States, 29401-5799
      • Veterans Affairs Medical Center - Charleston
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • University of Tennessee Cancer Institute at Methodist Central Hospital
  • Texas
    • Amarillo, Texas, United States, 79106
      • Veterans Affairs Medical Center - Amarillo
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Lackland Air Force Base, Texas, United States, 78236-5300
      • Wilford Hall Medical Center
    • Lubbock, Texas, United States, 79415-3364
      • UMC Southwest Cancer and Research Center
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78229
      • Veterans Affairs Medical Center - San Antonio (Murphy)
    • Temple, Texas, United States, 76504
      • Veterans Affairs Medical Center - Temple
  • Utah
    • Salt Lake City, Utah, United States, 84148
      • Veterans Affairs Medical Center - Salt Lake City
    • Salt Lake City, Utah, United States, 84132
      • Huntsman Cancer Institute at University of Utah
  • Washington
    • Seattle, Washington, United States, 98101
      • CCOP - Virginia Mason Research Center
    • Seattle, Washington, United States, 98108
      • Veterans Affairs Medical Center - Seattle
    • Seattle, Washington, United States, 98109-1024
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
    • Tacoma, Washington, United States, 98431-5000
      • Madigan Army Medical Center
    • Tacoma, Washington, United States, 98405-0986
      • CCOP - Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treatment; 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	Radiation: radiation therapy; Biological: therapeutic allogeneic lymphocytes; Procedure: peripheral blood stem cell transplantation; Drug: cyclosporine; Drug: mycophenolate mofetil; Other Names: MMF; Drug: fludarabine

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Peter McSweeney, MD, Rocky Mountain Cancer Centers - Denver Midtown

Study record dates

Study Major Dates

• Study Start: April 1, 2003
• Primary Completion (Actual): June 1, 2005
• Study Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: January 27, 2003
• First Submitted That Met QC Criteria: January 27, 2003
• First Posted (Estimate): January 28, 2003

Study Record Updates

• Last Update Posted (Estimate): March 25, 2015
• Last Update Submitted That Met QC Criteria: March 5, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myeloid leukemia in remission
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Fludarabine; Mycophenolic Acid; Cyclosporine; Cyclosporins
• Other Study ID Numbers: S0125 (Other Identifier: SWOG); U10CA032102 (U.S. NIH Grant/Contract)