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

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00053014
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 5
• Locations: 83
• Arm: 1
• Duration (Months): 38
• Patients Per Site: 0.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: therapeutic allogeneic lymphocytes; Drug: cyclosporine; Drug: fludarabine; Drug: mycophenolate mofetil; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Study Start Date: Apr 1, 2003
• Actual Primary Completion Date: Jun 1, 2005
• Actual Study Completion Date: Jun 1, 2006

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Overall Survival [1 year]

   measured from date of registration to study until death from any cause with patients still alive censored at date of last contact

Secondary Outcome Measures

1. Serious Adverse Events [9 months]

   Twice a week for the first two months, one time a week during month 3, one time every two weeks for months 4-9.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 69 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner Good Samaritan Medical Center	Phoenix	Arizona	United States	85006
2	Veterans Affairs Medical Center - Tucson	Tucson	Arizona	United States	85723
3	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona	United States	85724
4	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
5	Veterans Affairs Medical Center - Little Rock	Little Rock	Arkansas	United States	72205
6	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
7	Scripps Cancer Center at Scripps Clinic	La Jolla	California	United States	92037-1027
8	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90033
9	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095-1678
10	Veterans Affairs Outpatient Clinic - Martinez	Martinez	California	United States	94553
11	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center	Orange	California	United States	92868
12	Sutter Cancer Center	Sacramento	California	United States	95816
13	University of California Davis Cancer Center	Sacramento	California	United States	95817
14	Stanford Cancer Center at Stanford University Medical Center	Stanford	California	United States	94305-5408
15	General Robert Huyser Cancer Center at David Grant Medical Center	Travis Air Force Base	California	United States	94535
16	John Muir/Mt. Diablo Comprehensive Cancer Center	Walnut Creek	California	United States	94598
17	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Aurora	Colorado	United States	80010
18	Veterans Affairs Medical Center - Denver	Denver	Colorado	United States	80220
19	Veterans Affairs Medical Center - Tampa (Haley)	Tampa	Florida	United States	33612
20	CCOP - Atlanta Regional	Atlanta	Georgia	United States	30342-1701
21	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia	United States	30033
22	Dwight David Eisenhower Army Medical Center	Fort Gordon	Georgia	United States	30905-5650
23	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	96813
24	MBCCOP - Hawaii	Honolulu	Hawaii	United States	96813
25	Mountain States Tumor Institute - Boise	Boise	Idaho	United States	83712
26	Veterans Affairs Medical Center - Chicago Westside Hospital	Chicago	Illinois	United States	60612
27	Veterans Affairs Medical Center - Hines	Hines	Illinois	United States	60141
28	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153-5500
29	Indiana Blood and Marrow Transplantation	Beech Grove	Indiana	United States	46107
30	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7353
31	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
32	Veterans Affairs Medical Center - Wichita	Wichita	Kansas	United States	67218
33	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky	United States	40502-2236
34	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536-0084
35	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana	United States	70112
36	Tulane Cancer Center at Tulane University Hospital and Clinic	New Orleans	Louisiana	United States	70112
37	Veterans Affairs Medical Center - New Orleans	New Orleans	Louisiana	United States	70112
38	New Orleans Cancer Institute at Memorial Medical Center	New Orleans	Louisiana	United States	70115
39	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana	United States	71101-4295
40	Feist-Weiller Cancer Center at Louisiana State University Health Sciences	Shreveport	Louisiana	United States	71130-3932
41	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
42	Cancer Research Center at Boston Medical Center	Boston	Massachusetts	United States	02118
43	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0948
44	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
45	Veterans Affairs Medical Center - Detroit	Detroit	Michigan	United States	48201-1932
46	Josephine Ford Cancer Center at Henry Ford Health System	Detroit	Michigan	United States	48202
47	Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	Michigan	United States	48075
48	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
49	Veterans Affairs Medical Center - Jackson	Jackson	Mississippi	United States	39216
50	CCOP - Kansas City	Kansas City	Missouri	United States	64131
51	Saint Louis University Cancer Center	Saint Louis	Missouri	United States	63110
52	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
53	Veterans Affairs Medical Center - Albuquerque	Albuquerque	New Mexico	United States	87108-5138
54	Veterans Affairs Medical Center - Albany	Albany	New York	United States	12208
55	NYU Cancer Institute at New York University Medical Center	New York	New York	United States	10016
56	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York	United States	10032
57	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
58	Veterans Affairs Medical Center - Cincinnati	Cincinnati	Ohio	United States	45220-2288
59	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195-9001
60	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428-1002
61	CCOP - Dayton	Dayton	Ohio	United States	45429
62	Oklahoma University Medical Center	Oklahoma City	Oklahoma	United States	73104
63	Veterans Affairs Medical Center - Oklahoma City	Oklahoma City	Oklahoma	United States	73104
64	Cancer Institute at Oregon Health and Science University	Portland	Oregon	United States	97201-3098
65	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
66	Veterans Affairs Medical Center - Charleston	Charleston	South Carolina	United States	29401-5799
67	CCOP - Greenville	Greenville	South Carolina	United States	29615
68	University of Tennessee Cancer Institute at Methodist Central Hospital	Memphis	Tennessee	United States	38104
69	Veterans Affairs Medical Center - Amarillo	Amarillo	Texas	United States	79106
70	Baylor College of Medicine	Houston	Texas	United States	77030
71	Wilford Hall Medical Center	Lackland Air Force Base	Texas	United States	78236-5300
72	UMC Southwest Cancer and Research Center	Lubbock	Texas	United States	79415-3364
73	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229-3900
74	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas	United States	78229
75	Veterans Affairs Medical Center - Temple	Temple	Texas	United States	76504
76	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah	United States	84132
77	Veterans Affairs Medical Center - Salt Lake City	Salt Lake City	Utah	United States	84148
78	CCOP - Virginia Mason Research Center	Seattle	Washington	United States	98101
79	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98104
80	Veterans Affairs Medical Center - Seattle	Seattle	Washington	United States	98108
81	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109-1024
82	CCOP - Northwest	Tacoma	Washington	United States	98405-0986
83	Madigan Army Medical Center	Tacoma	Washington	United States	98431-5000

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Peter McSweeney, MD, Rocky Mountain Cancer Centers - Denver Midtown

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00053014
• Other Study ID Numbers: S0125; S0125; U10CA032102
• First Posted: Jan 28, 2003
• Last Update Posted: Mar 25, 2015
• Last Verified: Mar 1, 2015

• Keywords provided by Southwest Oncology Group: 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
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Cyclosporine; Mycophenolic Acid; Fludarabine; Cyclosporins

Study Results

Participant Flow

Arm/Group Title	Treatment
Arm/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 - CSP 6.25 mg/kg bid PO D -3 to +180 (begin taper on D+35); MMF 15mg/kg bid PO D0 to +27
Period Title: Overall Study
STARTED	5
COMPLETED	5
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment
Arm/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 - CSP 6.25 mg/kg bid PO D -3 to +180 (begin taper on D+35); MMF 15mg/kg bid PO D0 to +27
Overall Participants	5
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62
Sex: Female, Male (Count of Participants)
Female	1 20%
Male	4 80%
Region of Enrollment (participants) [Number]
United States	5 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/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 - CSP 6.25 mg/kg bid PO D -3 to +180 (begin taper on D+35); MMF 15mg/kg bid PO D0 to +27
Measure Participants	5
Number [participants]	1 20%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All patients

Arm/Group Title	Treatment
Arm/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 - CSP 6.25 mg/kg bid PO D -3 to +180 (begin taper on D+35); MMF 15mg/kg bid PO D0 to +27
Measure Participants	5
Number [participants]	0 0%

Adverse Events

Arm/Group Title	Treatment
Arm/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 - CSP 6.25 mg/kg bid PO D -3 to +180 (begin taper on D+35); MMF 15mg/kg bid PO D0 to +27
All Cause Mortality
	Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Other (Not Including Serious) Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	1/5 (20%)
Respiratory, thoracic and mediastinal disorders
Infection and dyspnea	1/5 (20%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.