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
  Purpose

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.


Condition Intervention Phase
Leukemia
Drug: arsenic trioxide
Drug: idarubicin
Drug: tretinoin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Combined All-Trans Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Molecular remission rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 1
Study Start Date: September 2007
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tretinoin and Arsenic Trioxide With or Without Idarubicin
See Outline for details
Drug: arsenic trioxide Drug: idarubicin Drug: tretinoin

  Hide Detailed Description

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00528450

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Cephalon
Investigators
Principal Investigator: Joseph G. Jurcic, MD Memorial Sloan-Kettering Cancer Center
Principal Investigator: Peter Maslak, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00528450     History of Changes
Other Study ID Numbers: 07-108, P30CA008748, MSKCC-07108, CEPHALONO-MSKCC-07108
Study First Received: September 10, 2007
Last Updated: March 15, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
adult acute promyelocytic leukemia (M3)
adult acute myeloid leukemia with t(15;17)(q22;q12)
untreated adult acute myeloid leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Idarubicin
Arsenic trioxide
Tretinoin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Keratolytic Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on July 23, 2014