Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 16 of 34 for:    "Acute Promyelocytic Leukemia" | "Arsenic trioxide"

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00528450
Recruitment Status : Terminated (Lack of accrual)
First Posted : September 12, 2007
Results First Posted : January 29, 2016
Last Update Posted : January 29, 2016
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Cephalon
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE September 10, 2007
First Posted Date  ICMJE September 12, 2007
Results First Submitted Date  ICMJE December 23, 2015
Results First Posted Date  ICMJE January 29, 2016
Last Update Posted Date January 29, 2016
Study Start Date  ICMJE September 2007
Actual Primary Completion Date January 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 23, 2015)
Molecular Remission Rate [ Time Frame: 2 years ]
# of patients with Complete Remission
Original Primary Outcome Measures  ICMJE
 (submitted: September 10, 2007)
Molecular Remission Rate
Change History Complete list of historical versions of study NCT00528450 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2007)
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tretinoin and Arsenic Trioxide With or Without Idarubicin in Treating Patients With Acute Promyelocytic Leukemia
Official Title  ICMJE Phase II Study of Combined All-Trans Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy
Brief Summary

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.

Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leukemia
Intervention  ICMJE
  • Drug: arsenic trioxide
  • Drug: idarubicin
  • Drug: tretinoin
Study Arms  ICMJE Experimental: Tretinoin and Arsenic Trioxide With or Without Idarubicin
See Outline for details
Interventions:
  • Drug: arsenic trioxide
  • Drug: idarubicin
  • Drug: tretinoin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 15, 2013)
1
Original Enrollment  ICMJE
 (submitted: September 10, 2007)
39
Actual Study Completion Date  ICMJE January 2011
Actual Primary Completion Date January 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00528450
Other Study ID Numbers  ICMJE 07-108
P30CA008748 ( U.S. NIH Grant/Contract )
MSKCC-07108
CEPHALONO-MSKCC-07108
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Cephalon
Investigators  ICMJE
Principal Investigator: Joseph G. Jurcic, MD Memorial Sloan Kettering Cancer Center
Principal Investigator: Peter Maslak, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date December 2015

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