Clinical trial NCT00020111: Arsenic Trioxide in Treating Young Patients With Refractory Leukemia or Lymphoma
Official title: Phase I Trial and Pharmacokinetic Study of Arsenic Trioxide in Pediatric Patients With Refractory Leukemia or Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia
Lymphoma
Keywords: recurrent childhood acute myeloid leukemia
childhood acute promyelocytic leukemia (M3)
recurrent childhood acute lymphoblastic leukemia
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
recurrent childhood small noncleaved cell lymphoma
recurrent/refractory childhood Hodgkin lymphoma
childhood chronic myelogenous leukemia
atypical chronic myeloid leukemia, BCR-ABL1 negative
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital at Stanford University Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
city: Torrance
country: United States
facility: County of Los Angeles Harbor-UCLA Medical Center
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Atlanta
country: United States
facility: AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus
state: Georgia
city: Chicago
country: United States
facility: Children's Memorial Hospital - Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Children Cancer Center at Riley Hospital for Children
state: Indiana
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
city: Boston
country: United States
facility: Floating Hospital for Children
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Cardinal Glennon Children's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Hackensack
country: United States
facility: Cancer Center at Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Medical Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Children's Hospital
state: Tennessee
city: Dallas
country: United States
facility: Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center - Fort Worth
state: Texas
city: Houston
country: United States
facility: Texas Children's Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center at University of Texas
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at University of Utah
state: Utah
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center
state: Wisconsin
city: Parkville
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Montreal Children's Hospital at McGill University Health Center
state: Quebec
city: Montreal
country: Canada
facility: Hopital Sainte Justine
state: Quebec
Study officials:
affiliation: National Cancer Institute (NCI)
name: Frank M. Balis, MD
role: STUDY_CHAIR
References:
citation: 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, including acute promyelocytic leukemia or lymphoma. Blood. 2008 Jan 15;111(2):566-73. doi: 10.1182/blood-2007-08-107839. Epub 2007 Oct 24.
citation: 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.