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Phase II Study of Tretinoin and Arsenic Trioxide With or Without Idarubicin in Patients With Acute Promyelocytic Leukemia
Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information
Alternate Title
Tretinoin and Arsenic Trioxide With or Without Idarubicin in Treating Patients With Acute Promyelocytic Leukemia
Basic Trial Information
| Phase | Type | Status | Age | Protocol IDs |
|---|
| Phase II | Treatment | Closed | 18 and over | MSKCC-07108
IRB 07-108, CEPHALONO-MSKCC-07108, NCT00528450 |
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.
Entry 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
Prior/Concurrent Therapy:
- No prior treatment for APL
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
Expected Enrollment 39Outcomes Primary Outcome(s)Molecular remission rate
Secondary Outcome(s)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
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.
After completion of study therapy, patients are followed periodically.
Trial Contact Information
Trial Lead Organizations Memorial Sloan-Kettering Cancer Center | | | | Joseph Jurcic, MD, Principal investigator | | | | | Peter Maslak, MD, Principal investigator | | | |
| Registry Information | | | Official Title | | Phase II Study of Combined All-Trans Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy | | | Trial Start Date | | 2007-09-20 | | | Trial Completion Date | | 2012-12-10 (estimated) | | | Registered in ClinicalTrials.gov | | NCT00528450 | | | Date Submitted to PDQ | | 2007-08-16 | | | Information Last Verified | | 2008-12-14 | | | NCI Grant/Contract Number | | CA08748 |
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.  Back to Top |
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