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Clinical Trials (PDQ®)

  • First Published: 3/19/2009
  • Last Modified: 11/6/2012

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Phase III Study of Risk-Adapted Induction Chemotherapy, Risk-Adapted Consolidation Combination Chemotherapy Including Arsenic Trioxide, and Maintenance Combination Chemotherapy in Young Patients With Newly Diagnosed Acute Promyelocytic Leukemia

Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Promyelocytic Leukemia

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIIBiomarker/Laboratory analysis, TreatmentTemporarily closed2 to 21NCICOG-AAML0631
COG-AAML0631, AAML0631, NCT00866918

Objectives

Primary

  1. To decrease the total anthracycline dose from the best current published results in patients with standard-risk childhood acute promyelocytic leukemia (APL) while still maintaining a comparable event-free survival (EFS).

Secondary

  1. To assign treatment based on risk stratification by WBC at diagnosis.
  2. To estimate the induction failure rate, toxic death rate, disease-free survival rate, and overall survival rate in both standard- and high-risk APL patients.
  3. To monitor for cardiotonicity in an idarubicin/mitoxantrone hydrochloride-based regimen.
  4. To document the toxicity of a traditional chemotherapy/tretinoin-based regimen combined with arsenic trioxide therapy.
  5. To compare the EFS of children enrolled on this study with the EFS of children enrolled on CALGB-C9710 who were between the ages of 2 and 21 and did not receive arsenic trioxide.
  6. To estimate the proportion of patients who carry a cryptic t(15;17), i.e., those who are positive for a PML-RARA fusion transcript by PCR analysis but have normal chromosomes.
  7. To estimate the proportion of patients with variant RARA partners.
  8. To compare the outcome of patients with only a t(15;17) with that of patients who carry a t(15;17) and other chromosomal abnormalities.

Entry Criteria

Disease Characteristics:

  • New clinically and morphologically confirmed diagnosis of acute promyelocytic leukemia (APL) (bone marrow or peripheral blood)
    • Bone marrow is highly preferred but in cases where marrow cannot be obtained at diagnosis, peripheral blood will be accepted

  • If the real-time quantitative (RQ)-PCR results are known, the patient must demonstrate PML-RARA and/or RARA-PML transcripts by RQ-PCR

  • Patients without evidence of APL by bone marrow or peripheral blood morphology but with isolated myeloid sarcoma (myeloblastoma; chloroma, including leukemia cutis) are eligible provided that the t(15;17) translocation is documented on either marrow or tumor tissue by cytogenetics, FISH, or PCR prior to study enrollment (in this situation, touch preps from the tumor site can be evaluated by FISH with PML-RARA probes)

Prior/Concurrent Therapy:

  • Prior intrathecal cytarabine prior to the diagnosis of acute promyelocytic leukemia (APL) allowed
  • Prior corticosteroids, hydroxyurea, and leukapheresis allowed
  • No prior systemic definitive treatment for APL or other suspected leukemia, including cytotoxic chemotherapy, retinoids, or arsenic

Patient Characteristics:

  • No minimal performance status criteria
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No pre-existing prolonged QT syndrome

Expected Enrollment

132

Outcomes

Primary Outcome(s)

Event-free survival

Secondary Outcome(s)

Hematologic, molecular, and cytogenetic remission rates after each phase of therapy
Overall survival
Percentage of patients experiencing grade 3 or 4 toxicity, or cardiac toxicity of any grade
Time to blood count recovery
Duration of hospitalization

Outline

This is a multicenter study. Patients are treated based on risk factor (standard-risk [WBC < 10,000/mm3] or high-risk [WBC ≥ 10,000/mm3]).

  • Induction therapy:
    • Standard-risk: Patients receive oral tretinoin twice daily on days 1-30 and idarubicin IV over 15 minutes once on days 3, 5, and 7.
    • High-risk: Patients receive oral tretinoin twice daily on days 1-30 and idarubicin IV over 15 minutes once on days 1, 3, and 5.

    Patients proceed to consolidation therapy one week later or when blood counts recover.

  • Consolidation therapy:
    • Consolidation 1: Patients receive arsenic trioxide IV over 2 hours on days 1-5, 8-12, 15-19, 22-26, and 29-33 and oral tretinoin twice daily on days 1-14. Treatment repeats every 5 weeks for 2 courses, followed by a 2-week break, and then treatment repeats for 2 more courses. Beginning 1 week later or when blood counts recover, patients proceed to consolidation 2.
    • Consolidation 2: Patients receive cytarabine intrathecally (IT) on day 1, oral tretinoin twice daily on days 1-14, high-dose cytarabine IV over 3 hours every 12 hours on days 1-3, and mitoxantrone hydrochloride IV over 15-30 minutes once on days 3 and 4. Patients proceed to consolidation 3 one week later or when blood counts recover.
    • Consolidation 3: Patients receive cytarabine IT on day 1, oral tretinoin twice daily on days 1-14, and idarubicin IV over 15 minutes once daily on days 1, 3, and 5. High-risk patients and those standard-risk patients who are positive for minimal residual disease by real-time quantitative (RQ)-PCR receive consolidation 4 one week later or when blood counts recover. All other standard-risk patients proceed to maintenance therapy.
    • Consolidation 4 (patients with high-risk cytology): Patients receive cytarabine IT on day 1, oral tretinoin twice daily on days 1-14, high-dose cytarabine IV over 3 hours every 12 hours on days 1-3, and idarubicin IV over 15 minutes once on day 4. Patients who demonstrate molecular complete remission (CR) and remain in hematological CR proceed to maintenance therapy 1 week later or when blood counts recover.

  • Maintenance therapy: Patients receive cytarabine IT on day 1 (course 1 only), oral tretinoin twice daily on days 1-14, oral mercaptopurine once daily on days 1-84, oral methotrexate once on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for 9 courses.

Bone marrow or blood is collected at baseline and then periodically during the study for RQ-PCR analysis. Tumor tissue is collected at baseline for cytogenetic analysis.

After completion of study treatment, patients are followed every month for 1 year, every 3 months for 2 years, every 6 months for 2 years, and then annually for 5 years.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

John Gregory, MD, Protocol chair
Ph: 973-971-6720
Email: john.gregoryjr@atlantichealth.org

Related Information

PDQ® clinical trial NCI-2012-02811

Registry Information
Official Title Risk Adapted Treatment of Newly Diagnosed Childhood Acute Promyelocytic Leukemia (APL) Using Arsenic Trioxide (Trisenox® IND #103331) During Consolidation
Trial Start Date 2009-03-09
Trial Completion Date 2015-06-09 (estimated)
Registered in ClinicalTrials.gov NCT00866918
Date Submitted to PDQ 2009-03-03
Information Last Verified 2012-11-06
NCI Grant/Contract Number CA98543

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.

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