Combination Chemotherapy in Treating Patients With Acute Promyelocytic Leukemia

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00276601
First received: January 12, 2006
Last updated: April 16, 2014
Last verified: April 2014
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy works in treating patients with acute promyelocytic leukemia.


Condition Intervention Phase
Leukemia
Drug: arsenic trioxide
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: mercaptopurine
Drug: methotrexate
Drug: tretinoin
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Pilot Study of Arsenic Trioxide-Based Consolidation Therapy for the Primary Treatment of Acute Promyelocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Disease-free survival at 2 and 5 years after study completion [ Designated as safety issue: No ]
  • Safety of arsenic trioxide following cytarabine and anthracycline immediately after study completion [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Validate peripheral blood real-time PCR for minimal disease monitoring as measured by real-time PCR for PML-RARalpha monthly for two years after study completion [ Designated as safety issue: No ]

Study Start Date: October 2004
Study Completion Date: June 2013
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine, preliminarily, the safety of incorporating arsenic trioxide (ATO) into cytarabine and daunorubicin hydrochloride-based consolidation therapy followed by tretinoin maintenance therapy in patients receiving induction tretinoin and daunorubicin hydrochloride with acute promyelocytic leukemia (APL) induced into remission with tretinoin and daunorubicin hydrochloride.
  • Determine, preliminarily, the efficacy of this strategy in inducing and maintaining molecular remissions in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study.

  • Induction therapy: Patients receive oral tretinoin twice daily on days 1-60 and daunorubicin hydrochloride IV on days 4, 6, and 8. Patients are evaluated between days 60-67 and proceed to consolidation therapy.
  • Consolidation therapy: Patients receive cytarabine IV continuously on days 1-3, daunorubicin hydrochloride IV on days 1-3, and arsenic trioxide IV over 1-2 hours once daily, 5 days a week, beginning on day 8 and continuing for 6 weeks. Patients with clinical and/or cytogenic, but not molecular, remission receive additional arsenic trioxide once daily, 5 days a week, for 30 doses (6 weeks). Patients achieving clinical and molecular remission after completion of 6 or 12 weeks of arsenic trioxide proceed to maintenance therapy.
  • Maintenance therapy: Patients receive oral tretinoin once daily on days 1-15. Treatment repeats every 3 months for 8 courses (2 years).

After completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   5 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of acute promyelocytic leukemia (APL) by morphologic and flow cytometric documentation (high orthogonal light scatter, lack of HLA-DR expression)

    • Patients with classical APL as well as the microgranular variant (M3V) are eligible

      • In cases where the diagnosis is unclear, consultation with a hematopathologist is required before enrolling the patient in the study
  • Patients found to have cytogenetic abnormalities that do not produce the PML-RARα gene rearrangement will be removed from study and will not be included in data analysis

PATIENT CHARACTERISTICS:

  • Patients will not be excluded because of performance status or comorbid disease
  • Premenopausal female patients must have a negative pregnancy test

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy for APL except hydroxyurea
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00276601

Locations
United States, Alabama
Comprehensive Cancer Center at University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Florida
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
United States, Georgia
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, United States, 30342
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-3330
United States, Pennsylvania
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Study Chair: Steven D. Gore, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Steven D. Gore, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00276601     History of Changes
Other Study ID Numbers: J0442, CDR0000449985, P30CA006973, JHOC-J0442, WIRB-20041058
Study First Received: January 12, 2006
Last Updated: April 16, 2014
Health Authority: United States: Federal Government

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
untreated adult acute myeloid leukemia
untreated childhood acute myeloid leukemia and other myeloid malignancies
adult acute promyelocytic leukemia (M3)
childhood acute promyelocytic leukemia (M3)
adult acute myeloid leukemia with t(15;17)(q22;q12)

Additional relevant MeSH terms:
Leukemia
Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid, Acute
Leukemia, Myeloid
6-Mercaptopurine
Cytarabine
Methotrexate
Arsenic trioxide
Daunorubicin
Tretinoin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Antiviral Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on April 22, 2014