Arsenic Trioxide in Treating Young Patients With Refractory Leukemia or Lymphoma

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00020111

Collaborator

(none)

Locations

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.

PURPOSE: This phase I trial is studying the side effects and best dose of arsenic trioxide in treating young patients with leukemia or lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Lymphoma	Drug: arsenic trioxide	Phase 1

Detailed Description

OBJECTIVES:

Determine the toxic effects of arsenic trioxide in pediatric patients with refractory leukemia or lymphoma.
Determine the maximum tolerated dose of this drug in this patient population.
Determine the plasma pharmacokinetics of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to disease (acute promyelocytic leukemia [APL] vs non-APL).

Stratum I (APL patients): Patients receive standard-dose arsenic trioxide IV over 2 hours daily 5 days a week for 4 weeks. Treatment continues every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Stratum II (Non-APL patients): Cohorts of 3-6 patients receive escalating doses of arsenic trioxide (according to the stratum 1 schedule above) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with arsenic trioxide at the recommended phase II dose.

Leukemia patients in both strata without progressive disease who have not achieved complete remission after the first 20 doses may continue to receive arsenic trioxide for 2 additional weeks.

Patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A maximum of 18 patients will be accrued for stratum I of this study within 2-3 years. A total of 3-30 patients will be accrued for stratum II of this study within 1-2 years.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

Phase I Trial and Pharmacokinetic Study of Arsenic Trioxide in Pediatric Patients With Refractory Leukemia or Lymphoma

Study Start Date :

Mar 1, 2000

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed leukemia or lymphoma refractory to standard curative treatment regimens
Measurable or evaluable disease
No meningeal leukemia or lymphoma
No HIV-related lymphoma
No lymphoproliferative diseases

PATIENT CHARACTERISTICS:

Age:

2 to 21
Acute promyelocytic leukemia (APL) patients (stratum I) must be age 2 to 12

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

Bilirubin normal
SGPT less than 2 times upper limit of normal
No significant hepatic dysfunction that would preclude study therapy

Renal:

Creatinine normal (age adjusted) OR
Creatinine clearance at least 60 mL/min
Potassium, magnesium, and calcium at least lower limit of normal (oral or IV supplementation allowed)
No significant renal dysfunction that would preclude study therapy

Cardiovascular:

Rate corrected QTc interval no greater than 0.48 on EKG
No significant cardiac dysfunction that would preclude study therapy
No cardiac disease, including dysrhythmias

Pulmonary:

No significant pulmonary dysfunction that would preclude study therapy

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No persistent grade 3 or greater sensory or motor neuropathy
No prior grand mal seizures (grade 3 or greater) within the past 2 years other than febrile seizures (except for patients with APL at discretion of investigator)
No clinically significant unrelated systemic illness that would preclude study therapy (e.g., serious infection)
HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

At least 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], and epoetin alfa)
No concurrent immunotherapy

Chemotherapy:

No prior arsenic trioxide
At least 2 weeks since prior chemotherapy (4 weeks for nitrosoureas) and recovered
No concurrent intrathecal chemotherapy except for acute promyelocytic leukemia (APL) patients experiencing progressive meningeal leukemia and demonstrating benefit from arsenic trioxide for systemic disease
No other concurrent anticancer chemotherapy

Endocrine therapy:

No concurrent steroids (except corticosteroids for retinoic acid syndrome)

Radiotherapy:

At least 4 weeks since prior radiotherapy and recovered
No concurrent radiotherapy

Surgery:

Not specified

Other:

At least 6 months since prior anticonvulsants
At least 1 week since prior retinoid therapy
No concurrent retinoids
No other concurrent investigational agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
2	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
3	Rebecca and John Moores UCSD Cancer Center	La Jolla	California	United States	92103-8447
4	Children's Hospital Los Angeles	Los Angeles	California	United States	90027-0700
5	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
6	Children's Hospital of Orange County	Orange	California	United States	92868
7	Lucile Packard Children's Hospital at Stanford University Medical Center	Palo Alto	California	United States	94304
8	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94143
9	County of Los Angeles Harbor-UCLA Medical Center	Torrance	California	United States	90509
10	Children's National Medical Center	Washington	District of Columbia	United States	20010-2970
11	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus	Atlanta	Georgia	United States	30342
12	Children's Memorial Hospital - Chicago	Chicago	Illinois	United States	60614
13	Riley Children Cancer Center at Riley Hospital for Children	Indianapolis	Indiana	United States	46202-5225
14	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
15	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
16	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland	United States	20892-1182
17	Floating Hospital for Children	Boston	Massachusetts	United States	02111
18	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
19	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0914
20	Children's Hospital of Michigan	Detroit	Michigan	United States	48201
21	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
22	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
23	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
24	Cardinal Glennon Children's Hospital	Saint Louis	Missouri	United States	63104
25	St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110
26	Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
27	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York	United States	10016
28	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
29	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York	United States	10032
30	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
31	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
32	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229-2899
33	Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University	Cleveland	Ohio	United States	44106-5065
34	Oklahoma University Medical Center	Oklahoma City	Oklahoma	United States	73126
35	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
36	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
37	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105-2794
38	Vanderbilt Children's Hospital	Nashville	Tennessee	United States	37232-6310
39	Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390-9063
40	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas	United States	76104
41	Texas Children's Cancer Center	Houston	Texas	United States	77030-2399
42	MD Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
43	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-7811
44	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah	United States	84112
45	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105
46	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
47	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
48	Royal Children's Hospital	Parkville	Victoria	Australia	3052
49	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6001
50	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
51	Montreal Children's Hospital at McGill University Health Center	Montreal	Quebec	Canada	H3H 1P3
52	Hopital Sainte Justine	Montreal	Quebec	Canada	H3T 1C5