Arsenic Trioxide in Treating Young Patients With Refractory Leukemia or Lymphoma

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00020111
First received: July 11, 2001
Last updated: May 14, 2011
Last verified: February 2005
  Purpose

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 Intervention Phase
Leukemia
Lymphoma
Drug: arsenic trioxide
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I Trial and Pharmacokinetic Study of Arsenic Trioxide in Pediatric Patients With Refractory Leukemia or Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: March 2000
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

Ages Eligible for Study:   2 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00020111

  Show 52 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Frank M. Balis, MD National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00020111     History of Changes
Obsolete Identifiers: NCT00004548
Other Study ID Numbers: CDR0000067717, NCI-00-C-0070J, NCI-T99-0080
Study First Received: July 11, 2001
Last Updated: May 14, 2011
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Lymphoma
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Arsenic trioxide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 02, 2014