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

Phase 1
2 Years
21 Years
Not Enrolling
Leukemia, Lymphoma

Thank you

Trial Information

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


- 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

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.

Inclusion Criteria


- 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



- 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


- Not specified


- Bilirubin normal

- SGPT less than 2 times upper limit of normal

- No significant hepatic dysfunction that would preclude study therapy


- 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


- 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


- No significant pulmonary dysfunction that would preclude study therapy


- 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


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


- 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)


- At least 4 weeks since prior radiotherapy and recovered

- No concurrent radiotherapy


- Not specified


- At least 6 months since prior anticonvulsants

- At least 1 week since prior retinoid therapy

- No concurrent retinoids

- No other concurrent investigational agents

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Frank M. Balis, MD

Investigator Role:

Study Chair

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

March 2000

Completion Date:

Related Keywords:

  • Leukemia
  • Lymphoma
  • 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
  • Leukemia
  • Lymphoma



Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Jonsson Comprehensive Cancer Center, UCLALos Angeles, California  90095-1781
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Children's Hospital of MichiganDetroit, Michigan  48201
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Midwest Children's Cancer CenterMilwaukee, Wisconsin  53226
NYU School of Medicine's Kaplan Comprehensive Cancer CenterNew York, New York  10016
University of Wisconsin Comprehensive Cancer CenterMadison, Wisconsin  53792
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's Hospital of Orange CountyOrange, California  92668
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Mercy HospitalKansas City, Missouri  64108
Children's Hospital of PittsburghPittsburgh, Pennsylvania  15213
Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105
Rebecca and John Moores UCSD Cancer CenterLa Jolla, California  92093-0658
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, Massachusetts  02115
Floating Hospital for ChildrenBoston, Massachusetts  02111
Cardinal Glennon Children's HospitalSaint Louis, Missouri  63104
St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794
Cook Children's Medical Center - Fort WorthFort Worth, Texas  76104
Texas Children's Cancer CenterHouston, Texas  77030-2399
City of Hope Comprehensive Cancer CenterDuarte, California  91010
UCSF Comprehensive Cancer CenterSan Francisco, California  94115
St. Louis Children's HospitalSaint Louis, Missouri  63110
Arkansas Cancer Research Center at University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Kansas Masonic Cancer Research Institute at the University of Kansas Medical CenterKansas City, Kansas  66160-7353
Herbert Irving Comprehensive Cancer Center at Columbia UniversityNew York, New York  10032
Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve UniversityCleveland, Ohio  44106
Oklahoma University Medical CenterOklahoma City, Oklahoma  73104
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Lucile Packard Children's Hospital at Stanford University Medical CenterPalo Alto, California  95798
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite CampusAtlanta, Georgia  30342
Riley Children Cancer Center at Riley Hospital for ChildrenIndianapolis, Indiana  46202-5225
Cancer Center at Hackensack University Medical CenterHackensack, New Jersey  07601
Vanderbilt Children's HospitalNashville, Tennessee  37232-6310
Simmons Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390-9063
Huntsman Cancer Institute at University of UtahSalt Lake City, Utah  84112
Warren Grant Magnuson Clinical Center - NCI Clinical Studies SupportBethesda, Maryland  20892-1182
MD Anderson Cancer Center at University of TexasHouston, Texas  77030-4009
County of Los Angeles Harbor-UCLA Medical CenterTorrance, California  90509