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Tretinoin and Arsenic Trioxide With or Without Idarubicin in Treating Patients With Acute Promyelocytic Leukemia

This study has been completed.
Sponsor:
Collaborators:
Cephalon
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00528450
First received: September 10, 2007
Last updated: March 15, 2013
Last verified: March 2013

September 10, 2007
March 15, 2013
September 2007
January 2011   (final data collection date for primary outcome measure)
Molecular remission rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Molecular remission rate
Complete list of historical versions of study NCT00528450 on ClinicalTrials.gov Archive Site
  • Clinical complete remission rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Proportion of patients who negative for disease by RT-PCR at study entry, after induction therapy, after each course of tretinoin (ATRA) and arsenic trioxide, and after each course of ATRA and idarubicin [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Median time to clinical and molecular remissions [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Toxicity as measured by NCI CTCAE version 3.0 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Number of hospitalizations and number of hospital days [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Incidence of secondary myelodysplastic syndromes/acute myeloid leukemia [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Comparison of the results of quantitative real-time RT-PCR assays for the PML-RARα transcript on bone marrow and peripheral blood [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Correlation of immunophenotyping of peripheral blood during induction therapy with expression of surface antigens, including CD33 and CD11b, over time [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Clinical complete remission rate
  • Proportion of patients who negative for disease by RT-PCR at study entry, after induction therapy, after each course of tretinoin (ATRA) and arsenic trioxide, and after each course of ATRA and idarubicin
  • Median time to clinical and molecular remissions
  • Disease-free survival
  • Overall survival
  • Toxicity as measured by NCI CTCAE version 3.0
  • Number of hospitalizations and number of hospital days
  • Incidence of secondary myelodysplastic syndromes/acute myeloid leukemia
  • Comparison of the results of quantitative real-time RT-PCR assays for the PML-RARα transcript on bone marrow and peripheral blood
  • Correlation of immunophenotyping of peripheral blood during induction therapy with expression of surface antigens, including CD33 and CD11b, over time
Not Provided
Not Provided
 
Tretinoin and Arsenic Trioxide With or Without Idarubicin in Treating Patients With Acute Promyelocytic Leukemia
Phase II Study of Combined All-Trans Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy

RATIONALE: Tretinoin may help cancer cells become more like normal cells, and to grow and spread more slowly. Drugs used in chemotherapy, such as arsenic trioxide and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving tretinoin together with arsenic trioxide with or without idarubicin may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving tretinoin together with arsenic trioxide with or without idarubicin works in treating patients with acute promyelocytic leukemia.

OBJECTIVES:

Primary

  • To determine the rate of molecular remission after induction therapy comprising tretinoin (ATRA) and arsenic trioxide (ATO) (along with idarubicin in patients with leukocytosis) in patients with acute promyelocytic leukemia (APL).

Secondary

  • To determine the rate of clinical complete remission and the time to remission after induction therapy.
  • To determine the proportion of patients in molecular remission after each course of postremission therapy and to use these findings to direct the number of consolidation courses with ATRA and idarubicin that are administered.
  • To determine the disease-free survival and overall survival of patients treated with this regimen.
  • To determine the toxicity of this treatment regimen, including the number and length of hospitalizations, the incidence of secondary myelodysplastic syndromes or acute myeloid leukemia, and the effects of treatment on LVEF.
  • To characterize the differentiation of APL cells during treatment with combined ATRA and ATO using serial immunophenotyping studies of peripheral blood and bone marrow.
  • To compare the results of quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assays performed on bone marrow and peripheral blood.

OUTLINE:

  • Induction therapy: Patients receive tretinoin orally twice daily and arsenic trioxide IV over 1-4 hours once daily until a marrow remission is documented or for 60 days, whichever comes first. Patients with leukocytosis (WBC > 10,000/μL) also receive idarubicin IV over 10-15 minutes beginning on day 2 and continuing every other day for 4 doses. Patients who achieve a clinical complete remission (CR) proceed to consolidation therapy. If a marrow remission is not achieved after 60 days, the patient is removed from the study.
  • Consolidation therapy:

    • Consolidation courses 1, 2, and 3: Beginning 3-6 weeks after documentation of clinical CR, patients receive consolidation therapy comprising tretinoin orally twice daily for 15 days and arsenic trioxide IV over 1-4 hours once daily 5 days a week for 5 weeks. Consolidation therapy repeats every 3-6 weeks for 3 courses.

Patients who have a negative PML-RARα transcript by reverse transcriptase-polymerase chain reaction (RT-PCR) assay after consolidation course 2 proceed to maintenance therapy after receiving consolidation course 3. Patients who have a negative PML-RARα transcript by RT-PCR assay after consolidation course 3, proceed to consolidation course 4 followed by maintenance therapy. Patients who have a positive PML-RARα transcript by RT-PCR assay after consolidation courses 2 and 3 proceed to consolidation courses 4 and 5.

  • Consolidation course 4: Beginning 3-6 weeks after completion of consolidation course 3, patients receive tretinoin orally twice daily for 15 days and idarubicin IV over 10-15 minutes once daily for 4 days.
  • Consolidation course 5: Beginning 3-6 weeks after completion of consolidation course 4, patients receive tretinoin orally twice daily for 15 days and idarubicin IV over 10-15 minutes once daily for 3 days.

Patients who remain positive for the PML-RARα transcript after 5 courses of consolidation therapy are removed from the study. Patients who have a negative PML-RARα transcript after 5 courses of consolidation therapy proceed to maintenance therapy.

  • Maintenance therapy: Beginning approximately 3 months after completion of the final consolidation course, patients receive tretinoin orally twice daily for 15 days. Treatment repeats every 3 months for up to 2 years.

Disease status will be monitored with serial analyses of bone marrow and peripheral blood samples using RT-PCR for PML-RARα mRNA. Patients will be followed until relapse, death, loss to follow-up, or removal from study.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Leukemia
  • Drug: arsenic trioxide
  • Drug: idarubicin
  • Drug: tretinoin
Experimental: Tretinoin and Arsenic Trioxide With or Without Idarubicin
See Outline for details
Interventions:
  • Drug: arsenic trioxide
  • Drug: idarubicin
  • Drug: tretinoin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1
January 2011
January 2011   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Morphologic diagnosis of acute promyelocytic leukemia (APL), confirmed by one of the following:

    • Demonstration of t(15;17) using conventional cytogenetics or fluorescence in situ hybridization (FISH)
    • Positive PML-RARα transcript by reverse transcriptase-polymerase chain reaction (RT-PCR) assay
  • Patients with CNS involvement by APL are eligible

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 60-100%
  • Creatinine ≤ 2.0 mg/dL or creatinine clearance > 60 mL/min
  • Bilirubin < 2.0 mg/dL (unless attributed to Gilbert disease)
  • Alkaline phosphatase ≤ 2.5 times the upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 ULN
  • LVEF ≥ 50% on echocardiogram or MUGA scan
  • QTc ≤ 500 msec on baseline ECG
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 4 months after the completion of study treatment
  • No active serious infections not controlled by antibiotics
  • No other concurrent active malignancy requiring immediate therapy
  • No clinically significant cardiac disease (New York Heart Association class III or IV heart disease), including chronic arrhythmias
  • No pulmonary disease
  • No other serious or life-threatening condition deemed unacceptable by the principal investigator

PRIOR CONCURRENT THERAPY:

  • No prior treatment for APL
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00528450
07-108, P30CA008748, MSKCC-07108, CEPHALONO-MSKCC-07108
Not Provided
Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
  • National Cancer Institute (NCI)
  • Cephalon
Principal Investigator: Joseph G. Jurcic, MD Memorial Sloan-Kettering Cancer Center
Principal Investigator: Peter Maslak, MD Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP