Arsenic Trioxide in Treating Young Patients With Refractory Leukemia or Lymphoma

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00020111
• Other study ID #: CDR0000067717
• Secondary ID: NCI-00-C-0070JNC
• Status: Completed
• Phase: Phase 1
• First received: July 11, 2001
• Last updated: April 28, 2015
• Start date: March 2000

Study information

• Verified date: February 2005
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00004548

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 21 Years

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Lymphoma

Intervention

Drug:
• arsenic trioxide

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	Montreal Children's Hospital at McGill University Health Center	Montreal	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Floating Hospital for Children	Boston	Massachusetts
United States	Children's Memorial Hospital - Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University	Cleveland	Ohio
United States	Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	MD Anderson Cancer Center at University of Texas	Houston	Texas
United States	Texas Children's Cancer Center	Houston	Texas
United States	Riley Children Cancer Center at Riley Hospital for Children	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	Vanderbilt Children's Hospital	Nashville	Tennessee
United States	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	Oklahoma University Medical Center	Oklahoma City	Oklahoma
United States	Children's Hospital of Orange County	Orange	California
United States	Lucile Packard Children's Hospital at Stanford University Medical Center	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	St. Louis Children's Hospital	Saint Louis	Missouri
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	County of Los Angeles Harbor-UCLA Medical Center	Torrance	California
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

References & Publications (2)

Fox E, Adamson PC, Murgo A, et al.: Phase 1 trial and pharmacokinetic study of arsenic trioxide in children with refractory leukemia. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1582, 2002.

Fox E, Razzouk BI, Widemann BC, Xiao S, O'Brien M, Goodspeed W, Reaman GH, Blaney SM, Murgo AJ, Balis FM, Adamson PC. Phase 1 trial and pharmacokinetic study of arsenic trioxide in children and adolescents with refractory or relapsed acute leukemia, inclu — View Citation