Tretinoin, Cytarabine, and Daunorubicin Hydrochloride With or Without Arsenic Trioxide Followed by Tretinoin With or Without Mercaptopurine and Methotrexate in Treating Patients With Acute Promyelocytic Leukemia

NCT00003934 | Completed Phase 3

• 5 other identifiers: NCI-2012-02811C9710CDR0000067126CALGB-C9710U10CA031946
• Study Type: interventional
• Target: 420
• Locations: 1 country
• Sites: 2

Brief Summary

This randomized phase III trial is studying tretinoin and combination chemotherapy to see how well they work compared to tretinoin, combination chemotherapy, and arsenic trioxide in treating patients with acute promyelocytic leukemia that has not been treated previously. Drugs used in chemotherapy, such as daunorubicin, cytarabine, mercaptopurine, methotrexate, and arsenic trioxide, work in different ways to stop cancer cells from dividing so they stop growing or die. Tretinoin may help leukemia cells develop into normal white blood cells. It is not yet known which regimen is more effective for acute promyelocytic leukemia.

Conditions

Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

Outcome Measures

Primary Outcomes (5)

• Response rates

  Up to 10 years

• Distributions of event-free survival

  Up to 10 years

• Disease-free survival

  Time from the date of the maintenance randomization to relapse or death, assessed up to 10 years

• Survival

  Up to 10 years

• Toxicities for the various therapies graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0

  Up to 30 days after last dose of study treatment

Study Arms (2)

Arm I

EXPERIMENTAL

Induction: All patients receive oral tretinoin every 12 hours beginning on day 1 until complete response or for a maximum of 90 days. Patients also receive daunorubicin IV on days 3-6 and cytarabine IV continuously on days 3-9. Consolidation: All patients achieving CR or PR after completion of tretinoin, proceed to consolidation within 2 weeks of achieving CR or PR, but not prior to 30 days from the start of induction. Patients are randomized to 1 of 2 treatment arms. Patients receive oral tretinoin every 12 hours on days 1-7 and daunorubicin IV on days 1-2 or days 1-3, depending on age. Patients may receive an additional course. Treatment begins no earlier than 2 weeks and no later than 4 weeks after hematopoietic recovery.

Drug: tretinoin; Drug: daunorubicin hydrochloride; Drug: cytarabine; Drug: arsenic trioxide

Arm II

EXPERIMENTAL

Induction: All patients receive oral tretinoin every 12 hours beginning on day 1 until complete response or for a maximum of 90 days. Patients also receive daunorubicin IV on days 3-6 and cytarabine IV continuously on days 3-9. Consolidation: All patients achieving CR or PR after completion of tretinoin, proceed to consolidation within 2 weeks of achieving CR or PR, but not prior to 30 days from the start of induction. Patients are randomized to 1 of 2 treatment arms. Patients receive oral tretinoin as in arm I above. Patients also receive oral mercaptopurine once a day and oral methotrexate once weekly for up to 1 year.

Drug: tretinoin; Drug: daunorubicin hydrochloride; Drug: cytarabine; Drug: mercaptopurine; Drug: methotrexate; Drug: arsenic trioxide

Interventions

tretinoin DRUG

Given orally

Also known as: ATRA, Retin-A, TRA

Arm I; Arm II

daunorubicin hydrochloride DRUG

Given IV

Also known as: Cerubidin, Cerubidine, daunomycin hydrochloride, daunorubicin, RP-13057

Arm I; Arm II

cytarabine DRUG

Given IV

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside

Arm I; Arm II

mercaptopurine DRUG

Given IV

Also known as: 6-mercaptopurine, 6-MP, Leukerin, MP

Arm II

methotrexate DRUG

Given IV

Also known as: amethopterin, Folex, methylaminopterin, Mexate, MTX

Arm II

arsenic trioxide DRUG

Given IV

Also known as: Arsenic (III) Oxide, Arsenic Sesquioxide, Arsenous Acid Anhydride, AS2O3, Trisenox

Arm I; Arm II

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a clinical diagnosis of acute promyelocytic leukemia (APL) with proof of APL morphology (FAB-M3) confirmed by RT-PCR assay; a patient may be entered prior to completion of RT-PCR studies, but a patient who is subsequently found to be PML-RARα negative and RARα-PML negative will be removed from protocol treatment
• FAB clasification: the aspirate smear must show M3 characteristics and at least 30% of cells must be abnormal promyelocytes with heavy granulation; the overall marrow cellularity must be normocellular or hypercellular; patients with the microgranular variant (M3V) are eligible, and the diagnosis will be based on characteristic morphologic findings (e.g., reniform or bilobed nuclei)
• RT-PCR assay: submission of samples for RT-PCR assays for PML-RARα/RARα-PML transcripts is mandatory; the results do not have to be known prior to initiation of therapy; if the assay is subsequently found to be negative, the patient will be removed from protocol treatment and treated at the discretion of the responsible physician
• Prior treatment: the patient must not have received any systemic definitive treatment for APL, including cytotoxic chemotherapy or retinoids; prior therapy with corticosteroids, hydroxyurea or leukapheresis will not exclude the patient
• Non-pregnant, non-nursing: treatment under this protocol would expose an unborn child to significant risks; patients should not be pregnant or plan to become pregnant while on treatment; women and men of reproductive potential should agree to use an effective means of birth control; there is an extremely high risk of fetal malformation if pregnancy occurs while on ATRA in any amount even for short periods

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Cancer and Leukemia Group B

Chicago, Illinois, 60606, United States

Location

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

Related Publications (1)

• Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. doi: 10.1182/blood-2010-02-269621. Epub 2010 Aug 12.

  PMID: 20705755 DERIVED

MeSH Terms

Conditions

Leukemia, Promyelocytic, Acute

Interventions

Tretinoin; Daunorubicin; Cytarabine; Mercaptopurine; Methotrexate; merphos; Arsenic Trioxide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid, Acute; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sulfhydryl Compounds; Sulfur Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Aminopterin; Pterins; Pteridines; Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds

Study Officials

• Bayard Powell

  Cancer and Leukemia Group B

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: January 27, 2003
• Study Start: June 1, 1999
• Primary Completion: November 1, 2006
• Last Updated: June 5, 2013

Record last verified: 2013-06

Locations

US (2)