Tretinoin and Arsenic Trioxide With or Without Idarubicin in Treating Patients With Acute Promyelocytic Leukemia - Full Text View

Sponsor:	Memorial Sloan-Kettering Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00528450

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 II

Study Type:	Interventional
Study Design:	Treatment, Open Label
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:

MedlinePlus related topics: Arsenic Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Idarubicin hydrochloride Idarubicin Tretinoin Arsenic trioxide

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Molecular remission rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Clinical complete remission rate [ 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 [ Designated as safety issue: No ]
Median time to clinical and molecular remissions [ Designated as safety issue: No ]
Disease-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Toxicity as measured by NCI CTCAE version 3.0 [ Designated as safety issue: Yes ]
Number of hospitalizations and number of hospital days [ Designated as safety issue: No ]
Incidence of secondary myelodysplastic syndromes/acute myeloid leukemia [ 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 [ 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 [ Designated as safety issue: No ]

Estimated Enrollment:	39
Study Start Date:	September 2007
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

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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.

After completion of study therapy, patients are followed periodically.

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

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

National Cancer Institute (NCI)

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:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center ( Joseph G. Jurcic )
Study ID Numbers:	CDR0000563793, MSKCC-07108, CEPHALONO-MSKCC-07108
Study First Received:	September 10, 2007
Last Updated:	February 7, 2009
ClinicalTrials.gov Identifier:	NCT00528450 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adult acute promyelocytic leukemia (M3)
adult acute myeloid leukemia with t(15;17)(q22;q12)
untreated adult acute myeloid leukemia

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Antineoplastic Agents
Arsenic trioxide
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Antibiotics, Antineoplastic
Pharmacologic Actions
Keratolytic Agents

Leukemia
Neoplasms
Idarubicin
Therapeutic Uses
Leukemia, Promyelocytic, Acute
Tretinoin
Dermatologic Agents

ClinicalTrials.gov processed this record on November 27, 2009