Amifostine in Treating Young Patients With Newly Diagnosed De Novo Myelodysplastic Syndromes

Sponsor

Children's Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00098683

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Duration (Months)

0.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as amifostine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well amifostine works in treating young patients with newly diagnosed de novo myelodysplastic syndromes.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms	Drug: amifostine trihydrate	Phase 2

Detailed Description

OBJECTIVES:

Primary

Determine the hematologic effects of amifostine, in terms of, complete and partial response, in pediatric patients with newly diagnosed de novo myelodysplastic syndromes (MDS).
Determine the safety and efficacy of this drug in these patients.

Secondary

Determine the efficacy of this drug in preventing conversion of MDS to acute myeloid leukemia (AML) in terms of the proportion of patients who remain free of AML at the completion of study treatment.
Determine the duration of progression-free remission from MDS conversion to AML in patients treated with this drug.
Determine the effect of karyotypic abnormalities on survival and the duration from diagnosis of MDS until conversion to AML in patients treated with this drug.
Determine the effect of bone marrow blast count on survival and the duration from diagnosis of MDS until conversion to AML in patients treated with this drug.
Determine the effect of the number of cytopenias on survival in patients treated with this drug.
Correlate the duration of time from diagnosis of MDS until conversion to AML with survival in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive amifostine IV over 1-3 minutes on days 1, 3, 5, 8, 10, 12, 15, 17, and 19. Treatment repeats every 5 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease who are planning to undergo matched donor bone marrow or cord blood transplantation continue therapy until transplantation. Patients with stable or responding disease who are not undergoing transplantation may receive up to 4 additional courses of amifostine in the absence of disease progression or unacceptable toxicity.

Following completion of therapy with amifostine, patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 10-20 patients will be accrued for this study within 5-10 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study Of Amifostine In Children With Myelodysplastic Syndrome

Study Start Date :

Jan 1, 2005

Actual Primary Completion Date :

Oct 1, 2007

Actual Study Completion Date :

Oct 1, 2009

Outcome Measures

Primary Outcome Measures

Hematological effects (complete and partial response) []
Safety and efficacy []

Secondary Outcome Measures

Efficacy []
Duration of progression-free remission []
Effect of karyotypic abnormalities on survival []
Effect of the number of cytopenias on survival []
Correlation of the duration of time from diagnosis of myelodysplastic syndromes until conversion to acute myeloid leukemia []

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed diagnosis of myelodysplastic syndromes (MDS)
One of the following subtypes:
Refractory anemia (RA)
RA with ringed sideroblasts
RA with excess blasts
Refractory cytopenia with multilineage dysplasia (RCMD)
RCMD and ringed sideroblasts
MDS, unclassified
MDS associated with isolated del 5(q)
De novo disease
No treatment-induced MDS
No juvenile myelomonocytic leukemia
No Down syndrome, Fanconi's anemia, or other inherited forms of hypoplastic bone marrow failure

PATIENT CHARACTERISTICS:

Age

1 to 21 at original diagnosis

Performance status

Karnofsky 50-100% (patients > 16 years of age)
Lansky 50-100% (patients 1 to 16 years of age)

Life expectancy

At least 8 weeks

Hematopoietic

See Disease Characteristics

Hepatic

Bilirubin ≤ 1.5 times upper limit of normal (ULN)
ALT < 2.5 times ULN

Renal

Radioisotope glomerular filtration rate ≥ 60 mL/min OR
Creatinine clearance > 60 mL/min (based on Schwartz formula)
Calcium normal

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Serum electrolytes normal
Phosphorus normal
Magnesium normal
Glucose normal
No other concurrent malignancy

PRIOR CONCURRENT THERAPY:

Biologic therapy

More than 8 weeks since prior growth factors
No concurrent growth factors
No concurrent hematopoietic stem cell transplantation
No concurrent immunomodulating agents

Chemotherapy

No prior amifostine
No other concurrent anticancer chemotherapy

Endocrine therapy

No concurrent daily steroid therapy

Radiotherapy

Not specified

Surgery

Not specified

Other

No prior therapy for MDS

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016-7710
2	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
3	Jonathan Jaques Children's Cancer Center at Miller Children's Hospital	Long Beach	California	United States	90801
4	Children's Hospital Central California	Madera	California	United States	93638-8762
5	Kaiser Permanente Medical Center - Oakland	Sacramento	California	United States	95825
6	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut	United States	06360-2875
7	Lee Cancer Care of Lee Memorial Health System	Fort Myers	Florida	United States	33901
8	University of Florida Shands Cancer Center	Gainesville	Florida	United States	32610-0232
9	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida	United States	33021
10	Miami Children's Hospital	Miami	Florida	United States	33155
11	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida	United States	32504
12	All Children's Hospital	St. Petersburg	Florida	United States	33701
13	St. Joseph's Cancer Institute at St. Joseph's Hospital	Tampa	Florida	United States	33607
14	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida	United States	33407
15	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
16	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	95813
17	Advocate Christ Medical Center	Oak Lawn	Illinois	United States	60453
18	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202-5289
19	St. Vincent Indianapolis Hospital	Indianapolis	Indiana	United States	46260
20	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
21	Kosair Children's Hospital	Louisville	Kentucky	United States	40232
22	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
23	CancerCare of Maine at Eastern Maine Medial Center	Bangor	Maine	United States	04401
24	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland	United States	21215
25	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
26	Hurley Medical Center	Flint	Michigan	United States	48503
27	Spectrum Health Hospital - Butterworth Campus	Grand Rapids	Michigan	United States	49503-2560
28	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
29	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan	United States	48910
30	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
31	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
32	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
33	Siteman Cancer Center at Barnes-Jewish Hospital	St. Louis	Missouri	United States	63110
34	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-6805
35	Sunrise Hospital and Medical Center	Las Vegas	Nevada	United States	89109-2306
36	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey	United States	07601
37	Overlook Hospital	Morristown	New Jersey	United States	07962
38	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08901
39	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08903
40	University of New Mexico Cancer Research and Treatment Center	Albuquerque	New Mexico	United States	87131-5636
41	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York	United States	10461
42	Maimonides Cancer Center at Maimonides Medical Center	Brooklyn	New York	United States	11219
43	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York	United States	10032
44	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
45	New York Medical College	Valhalla	New York	United States	10595
46	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
47	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
48	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308-1062
49	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
50	Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106-5000
51	Columbus Children's Hospital	Columbus	Ohio	United States	43205-2696
52	Children's Medical Center - Dayton	Dayton	Ohio	United States	45404-1815
53	Tod Children's Hospital - Forum Health	Youngstown	Ohio	United States	44501
54	Oklahoma University Medical Center	Oklahoma City	Oklahoma	United States	73104
55	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
56	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104-9786
57	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134-1095
58	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
59	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
60	Greenville Hospital System Cancer Center	Greenville	South Carolina	United States	29605
61	East Tennessee Children's Hospital	Knoxville	Tennessee	United States	37916
62	Texas Tech University Health Sciences Center School of Medicine - Amarillo	Amarillo	Texas	United States	79106
63	Children's Hospital of Austin	Austin	Texas	United States	78701
64	Medical City Dallas Hospital	Dallas	Texas	United States	75230
65	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas	United States	76104-9958
66	Baylor University Medical Center - Houston	Houston	Texas	United States	77030-2399
67	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78207
68	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229-3993
69	Primary Children's Medical Center	Salt Lake City	Utah	United States	84113-1100
70	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105
71	West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division	Charleston	West Virginia	United States	25302
72	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia	United States	25701
73	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
74	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
75	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6001
76	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 1Z2
77	Children's & Women's Hospital of British Columbia	Vancouver	British Columbia	Canada	V6H 3V4
78	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
79	IWK Health Centre	Halifax	Nova Scotia	Canada	B3K 6R8
80	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8N 3Z5
81	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario	Canada	K7L 3N6
82	Montreal Children's Hospital at McGill University Health Center	Montreal	Quebec	Canada	H3H 1P3
83	Hopital Sainte Justine	Montreal	Quebec	Canada	H3T 1C5
84	Centre Hospitalier Universitaire de Quebec	Quebec		Canada	G1V 4G2
85	San Jorge Children's Hospital	Santurce		Puerto Rico	00912

Sponsors and Collaborators

Children's Oncology Group
National Cancer Institute (NCI)

Investigators

Study Chair: Prasad Mathew, MD, University of New Mexico Cancer Center
: Robert J. Arceci, MD, PhD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins