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

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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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Leukemia	Drug: arsenic trioxide Drug: idarubicin Drug: tretinoin	Phase 2

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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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	1 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Masking:	None (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
Study Start Date :	September 2007
Actual Primary Completion Date :	January 2011
Actual Study Completion Date :	January 2011

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Familial acute myeloid leukemia with mutated CEBPA Acute promyelocytic leukemia Cytogenetically normal acute myeloid leukemia Core binding factor acute myeloid leukemia

MedlinePlus related topics: Arsenic Leukemia

Drug Information available for: Tretinoin Arsenic trioxide Arsenic Idarubicin hydrochloride Idarubicin

Genetic and Rare Diseases Information Center resources: Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Acute Promyelocytic Leukemia

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Tretinoin and Arsenic Trioxide With or Without Idarubicin See Outline for details	Drug: arsenic trioxide Drug: idarubicin Drug: tretinoin

Outcome Measures

Primary Outcome Measures :

Molecular Remission Rate [ Time Frame: 2 years ]
# of patients with Complete Remission

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 120 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
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

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00528450

Locations

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United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

National Cancer Institute (NCI)

Cephalon

Investigators

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Principal Investigator:	Joseph G. Jurcic, MD	Memorial Sloan Kettering Cancer Center
Principal Investigator:	Peter Maslak, MD	Memorial Sloan Kettering Cancer Center

More Information

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Responsible Party:	Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00528450
Other Study ID Numbers:	07-108 P30CA008748 ( U.S. NIH Grant/Contract ) MSKCC-07108 CEPHALONO-MSKCC-07108
First Posted:	September 12, 2007 Key Record Dates
Results First Posted:	January 29, 2016
Last Update Posted:	January 29, 2016
Last Verified:	December 2015

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:

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Leukemia Leukemia, Promyelocytic, Acute Neoplasms by Histologic Type Neoplasms Leukemia, Myeloid, Acute Leukemia, Myeloid Idarubicin Arsenic Trioxide Tretinoin	Antibiotics, Antineoplastic Antineoplastic Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Keratolytic Agents Dermatologic Agents

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