Monoclonal Antibody Plus Chemotherapy in Treating Young Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes

Sponsor

Children's Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00028899

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

116

Duration (Months)

0.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as gemtuzumab ozogamicin can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with combination chemotherapy may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of combining gemtuzumab ozogamicin with combination chemotherapy in treating children who have relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Myelodysplastic Syndromes	Drug: asparaginase Drug: cytarabine Drug: gemtuzumab ozogamicin Drug: mitoxantrone hydrochloride	Phase 1

Detailed Description

OBJECTIVES:

Determine the safety and maximum tolerated dose of gemtuzumab ozogamicin in combination with conventional chemotherapy in patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndromes.
Determine the efficacy of this regimen in these patients.
Correlate the likelihood of leukemic blast cells to undergo apoptosis in vitro with the efficacy of this regimen in these patients.
Correlate drug resistance as manifested by dye efflux or multiple drug resistance-1 expression by leukemic blast cells with the efficacy of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study of gemtuzumab ozogamicin. Patients are assigned by cohort to 1 of 2 treatment regimens.

Regimen A: Patients receive cytarabine IV over 2 hours every 12 hours on days 1-4, mitoxantrone IV over 1 hour on days 3-6, and gemtuzumab ozogamicin IV over 2 hours on day 7.
Regimen B: Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 2, 8, and 9, asparaginase intramuscularly on days 2 and 9, and gemtuzumab ozogamicin IV over 2 hours on day 3.

Cohorts of 3-6 patients receive de-escalating doses of gemtuzumab ozogamicin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose below that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed monthly for 6 months, every 2 months for 6 months, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study within 1.5 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

47 participants

Primary Purpose:

Treatment

Official Title:

A Dose Finding Study of the Safety of Gemtuzumab Ozogamicin Combined With Conventional Chemotherapy for Patients With Relapsed or Refractory Acute Myeloid Leukemia

Study Start Date :

Jul 1, 2002

Actual Primary Completion Date :

Sep 1, 2006

Actual Study Completion Date :

Mar 1, 2012

Outcome Measures

Primary Outcome Measures

Event Free Survival [Length of study]

Secondary Outcome Measures

Toxicity []
Toxicity will be monitored through study chair notification and end course reports
Remission Rate [Length of study]
The remission rate in each arm will be estimated by the proportion of patients who achieved remission among patients who received GMTZ at the MTD level.
Prognostic Factor Analysis []
The predictive value of the likelihood of leukemia blast cells to undergo apoptosis and drug resistance of leukemia blast cells will be assessed by logistic regression

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of primary acute myeloid leukemia (AML) or myelodysplastic syndromes
Relapsed (remission duration less than 1 year) OR
Failed induction (failed to achieve an initial complete response)
Patients with AML as a second malignant neoplasm allowed provided no other prior therapy for AML
M2 or M3 bone marrow aspirate at time of study entry
No Fanconi's anemia
No known CNS leukemia

PATIENT CHARACTERISTICS:

Age:

21 and under

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

Bilirubin no greater than 1.5 times normal
AST or ALT less than 2.5 times upper limit of normal
No history of veno-occlusive disease of the liver defined as weight increase of more than 5% over baseline and serum bilirubin greater than 5 mg/dL within 20 days after receipt of chemotherapy

Renal:

Creatinine no greater than 1.5 times normal OR
Creatinine clearance or radioisotope glomerular filtration rate (GFR) at least 70 mL/min OR
Equivalent GFR by institutional normal range

Cardiovascular:

Shortening fraction more than 27% by echocardiogram or normal for institution OR
Ejection fraction more than 50% by MUGA

Other:

Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy:

At least 180 days since prior hematopoietic stem cell transplantation

Chemotherapy:

Not specified

Endocrine therapy:

Not specified

Radiotherapy:

Not specified

Surgery:

Not specified

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Comprehensive Cancer Center at University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016-7710
3	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	Jonathan Jaques Children's Cancer Center at Miller Children's Hospital	Long Beach	California	United States	90801
5	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
6	Children's Hospital of Orange County	Orange	California	United States	92868
7	Children's Hospital and Health Center - San Diego	San Diego	California	United States	92123-4282
8	Stanford Cancer Center at Stanford University Medical Center	Stanford	California	United States	94305
9	Children's Hospital Cancer Center	Denver	Colorado	United States	80218-1088
10	Children's National Medical Center	Washington	District of Columbia	United States	20010-2970
11	University of Florida Shands Cancer Center	Gainesville	Florida	United States	32610-0232
12	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida	United States	32803-1273
13	All Children's Hospital	St. Petersburg	Florida	United States	33701
14	St. Joseph's Cancer Institute at St. Joseph's Hospital	Tampa	Florida	United States	33607
15	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida	United States	33407
16	Emory University Hospital - Atlanta	Atlanta	Georgia	United States	30322
17	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	95813
18	Children's Memorial Hospital - Chicago	Chicago	Illinois	United States	60614
19	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202-5289
20	St. Vincent Indianapolis Hospital	Indianapolis	Indiana	United States	46260
21	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536-0084
22	CancerCare of Maine at Eastern Maine Medial Center	Bangor	Maine	United States	04401
23	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland	United States	21215
24	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
25	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
26	C.S. Mott Children's Hospital at University of Michigan	Ann Arbor	Michigan	United States	48109-0238
27	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
28	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
29	Children's Hospital of Minnesota - Minneapolis	Minneapolis	Minnesota	United States	55404
30	Fairview University Medical Center - University Campus	Minneapolis	Minnesota	United States	55455
31	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
32	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
33	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
34	Siteman Cancer Center at Barnes-Jewish Hospital	St. Louis	Missouri	United States	63110
35	Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
36	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08903
37	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
38	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York	United States	10032
39	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
40	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
41	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
42	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
43	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308-1062
44	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
45	Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106-5000
46	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195-5217
47	Columbus Children's Hospital	Columbus	Ohio	United States	43205-2696
48	Children's Medical Center - Dayton	Dayton	Ohio	United States	45404-1815
49	Tod Children's Hospital - Forum Health	Youngstown	Ohio	United States	44501
50	Oklahoma University Medical Center	Oklahoma City	Oklahoma	United States	73104
51	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104-9786
52	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
53	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
54	Greenville Hospital System Cancer Center	Greenville	South Carolina	United States	29605
55	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
56	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232-6310
57	Texas Tech University Health Sciences Center School of Medicine	Amarillo	Texas	United States	79106
58	Children's Hospital of Austin	Austin	Texas	United States	78701
59	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390
60	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas	United States	76104-9958
61	M.D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
62	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229-3993
63	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-7811
64	Massey Cancer Center at Virginia Commonwealth University	Richmond	Virginia	United States	23298-0037
65	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105
66	Providence Cancer Center at Sacred Heart Medical Center	Spokane	Washington	United States	99220-2555
67	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia	United States	25701
68	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
69	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
70	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
71	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6001
72	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8N 3Z5
73	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
74	McGill Cancer Centre at McGill University	Montreal	Quebec	Canada	H3H 1P3
75	Hopital Sainte Justine	Montreal	Quebec	Canada	H3T 1C5
76	Centre Hospitalier Universitaire de Quebec	Ste-Foy	Quebec	Canada	G1V 4G2