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
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Purpose
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
| Condition | Intervention | Phase |
|---|---|---|
|
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 |
Drug: tretinoin Drug: daunorubicin hydrochloride Drug: cytarabine Drug: mercaptopurine Drug: methotrexate Drug: arsenic trioxide |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase III Randomized Study of Concurrent Tretinoin and Chemotherapy With or Without Arsenic Trioxide (AS2O3) (NSC # 706363) as Initial Consolidation Therapy Followed by Maintenance Therapy With Intermittent Tretinoin Versus Intermittent Tretinoin Plus Mercaptopurine and Methotrexate for Patients With Untreated Acute Promyelocytic Leukemia |
- Response rates [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
- Distributions of event-free survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
- Disease-free survival [ Time Frame: Time from the date of the maintenance randomization to relapse or death, assessed up to 10 years ] [ Designated as safety issue: No ]
- Survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
- Toxicities for the various therapies graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 [ Time Frame: Up to 30 days after last dose of study treatment ] [ Designated as safety issue: Yes ]
| Enrollment: | 420 |
| Study Start Date: | June 1999 |
| Primary Completion Date: | November 2006 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I
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
Given orally
Other Names:
Drug: daunorubicin hydrochloride
Given IV
Other Names:
Drug: cytarabine
Given IV
Other Names:
Drug: arsenic trioxide
Given IV
Other Names:
|
|
Experimental: Arm II
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
Given orally
Other Names:
Drug: daunorubicin hydrochloride
Given IV
Other Names:
Drug: cytarabine
Given IV
Other Names:
Drug: mercaptopurine
Given IV
Other Names:
Drug: methotrexate
Given IV
Other Names:
Drug: arsenic trioxide
Given IV
Other Names:
|
Show Detailed Description Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
Contacts and Locations| United States, North Carolina | |
| Comprehensive Cancer Center of Wake Forest University | |
| Winston-Salem, North Carolina, United States, 27157 | |
| Principal Investigator: | Bayard Powell | Cancer and Leukemia Group B (CALGB) Research Base |
More Information
No publications provided by National Cancer Institute (NCI)
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00003934 History of Changes |
| Other Study ID Numbers: | NCI-2012-02811, CALGB C9710, U10CA031946, CDR0000067126 |
| Study First Received: | November 1, 1999 |
| Last Updated: | January 4, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Neoplasms Leukemia Leukemia, Myeloid, Acute Leukemia, Myeloid Leukemia, Promyelocytic, Acute Neoplasms by Histologic Type 6-Mercaptopurine Cytarabine Methotrexate Arsenic trioxide Daunorubicin Tretinoin Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
Antimetabolites, Antineoplastic Antineoplastic Agents Therapeutic Uses Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Antiviral Agents Anti-Infective Agents Antibiotics, Antineoplastic Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Dermatologic Agents |
ClinicalTrials.gov processed this record on May 16, 2013