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

Leukemia Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00053014
• Other study ID #: S0125
• Secondary ID: S0125U10CA032102
• Status: Terminated
• Phase: Phase 2
• First received: January 27, 2003
• Last updated: March 5, 2015
• Start date: April 2003
• Est. completion date: June 2006

Study information

• Verified date: March 2015
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: June 2006
• Est. primary completion date: June 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 55 Years to 69 Years

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Biological:
• therapeutic allogeneic lymphocytes

Drug:
• cyclosporine

• fludarabine

• mycophenolate mofetil

Procedure:
• peripheral blood stem cell transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Veterans Affairs Medical Center - Albany	Albany	New York
United States	Veterans Affairs Medical Center - Albuquerque	Albuquerque	New Mexico
United States	Veterans Affairs Medical Center - Amarillo	Amarillo	Texas
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Aurora	Colorado
United States	Indiana Blood and Marrow Transplantation	Beech Grove	Indiana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Mountain States Tumor Institute - Boise	Boise	Idaho
United States	Cancer Research Center at Boston Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Veterans Affairs Medical Center - Charleston	Charleston	South Carolina
United States	Veterans Affairs Medical Center - Chicago Westside Hospital	Chicago	Illinois
United States	Veterans Affairs Medical Center - Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	CCOP - Dayton	Dayton	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia
United States	Veterans Affairs Medical Center - Denver	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Josephine Ford Cancer Center at Henry Ford Health System	Detroit	Michigan
United States	Veterans Affairs Medical Center - Detroit	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Dwight David Eisenhower Army Medical Center	Fort Gordon	Georgia
United States	CCOP - Greenville	Greenville	South Carolina
United States	Veterans Affairs Medical Center - Hines	Hines	Illinois
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	MBCCOP - Hawaii	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Veterans Affairs Medical Center - Jackson	Jackson	Mississippi
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Scripps Cancer Center at Scripps Clinic	La Jolla	California
United States	Wilford Hall Medical Center	Lackland Air Force Base	Texas
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Veterans Affairs Medical Center - Little Rock	Little Rock	Arkansas
United States	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	UMC Southwest Cancer and Research Center	Lubbock	Texas
United States	Veterans Affairs Outpatient Clinic - Martinez	Martinez	California
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	University of Tennessee Cancer Institute at Methodist Central Hospital	Memphis	Tennessee
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	New Orleans Cancer Institute at Memorial Medical Center	New Orleans	Louisiana
United States	Tulane Cancer Center at Tulane University Hospital and Clinic	New Orleans	Louisiana
United States	Veterans Affairs Medical Center - New Orleans	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York
United States	NYU Cancer Institute at New York University Medical Center	New York	New York
United States	Oklahoma University Medical Center	Oklahoma City	Oklahoma
United States	Veterans Affairs Medical Center - Oklahoma City	Oklahoma City	Oklahoma
United States	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center	Orange	California
United States	Banner Good Samaritan Medical Center	Phoenix	Arizona
United States	Cancer Institute at Oregon Health and Science University	Portland	Oregon
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Sutter Cancer Center	Sacramento	California
United States	University of California Davis Cancer Center	Sacramento	California
United States	Saint Louis University Cancer Center	Saint Louis	Missouri
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	Veterans Affairs Medical Center - Salt Lake City	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	Veterans Affairs Medical Center - Seattle	Seattle	Washington
United States	Feist-Weiller Cancer Center at Louisiana State University Health Sciences	Shreveport	Louisiana
United States	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana
United States	Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	Michigan
United States	Stanford Cancer Center at Stanford University Medical Center	Stanford	California
United States	CCOP - Northwest	Tacoma	Washington
United States	Madigan Army Medical Center	Tacoma	Washington
United States	Veterans Affairs Medical Center - Tampa (Haley)	Tampa	Florida
United States	Veterans Affairs Medical Center - Temple	Temple	Texas
United States	General Robert Huyser Cancer Center at David Grant Medical Center	Travis Air Force Base	California
United States	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona
United States	Veterans Affairs Medical Center - Tucson	Tucson	Arizona
United States	John Muir/Mt. Diablo Comprehensive Cancer Center	Walnut Creek	California
United States	CCOP - Wichita	Wichita	Kansas
United States	Veterans Affairs Medical Center - Wichita	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes