Overview

This trial is active, not recruiting.

Condition leukemia
Treatments mercaptopurine, methotrexate, tretinoin
Phase phase 3
Sponsor Southwest Oncology Group
Collaborator National Cancer Institute (NCI)
Start date June 2007
End date December 2013
Trial size 105 participants
Trial identifier NCT00492856, S0521, U10CA032102

Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as gemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Sometimes the cancer may not need more treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether combination chemotherapy is more effective than observation when given as maintenance therapy in treating acute promyelocytic leukemia.

PURPOSE: This randomized phase III trial is studying tretinoin, mercaptopurine, and methotrexate to see how well they work when given as maintenance therapy compared with observation after combination chemotherapy in treating patients with acute promyelocytic leukemia. (Randomization and observation group closed as of 8/15/10)

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive oral tretinoin twice daily on days 1-7, oral mercaptopurine once daily on days 1-14, and oral methotrexate on day 1. Treatment repeats every 2 weeks for up to 1 year.
mercaptopurine
Given orally
methotrexate
Given orally
tretinoin
Given orally
(No Intervention)
Patients receive no further chemotherapy. Patients are followed every 3 months for 1 year. (Randomization and observation arm closed as of 8/15/10)

Primary Outcomes

Measure
3-year Disease-free Survival (DFS) Rate
time frame: Up to 3 years

Secondary Outcomes

Measure
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
time frame: Up to 5 years

Eligibility Criteria

Male or female participants at least 18 years old.

DISEASE CHARACTERISTICS: - Cytologically confirmed acute promyelocytic leukemia (APL) or the variant form of APL - Previously untreated disease - Low- or intermediate-risk disease - Low-risk disease, defined as white blood cell (WBC) ≤ 10,000/mm^3 and platelet count > 40,000/mm^3 - Intermediate-risk disease, defined as WBC ≤ 10,000/mm^3 and platelet count ≤ 40,000/mm^3 - WBC and platelet count confirming low- or intermediate-risk disease must be obtained within 48 hours prior to study registration unless the patient received tretinoin therapy prior to study registration in which case the WBC and platelet count must be obtained within 48 hours prior to study therapy - PML-RARα fusion gene positive by reverse transcriptase-polymerase chain reaction (RT-PCR) assay - No recurrent disease - Must be registered on clinical trials SWOG-9007 and SWOG-S9910 - Specimens must be collected prior to tretinoin therapy and may be collected after tretinoin therapy PATIENT CHARACTERISTICS: - Zubrod performance status 0-3 - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception for ≥ 1 month prior to, during, and for 2 months after completion of study treatment - No unstable cardiac arrhythmia or unstable angina - No other malignancy within the past 5 years except for the following: - Adequately treated basal cell or squamous cell skin cancer - Carcinoma in situ of the cervix - Adequately treated stage I or II cancer (except for highly aggressive malignancies with a high rate of early relapse) currently in complete remission PRIOR CONCURRENT THERAPY: - See Disease Characteristics - No more than 1 prior dose of intrathecal chemotherapy for acute leukemia - No prior systemic chemotherapy, hydroxyurea, or leukapheresis for acute leukemia - Prior tretinoin at a dose of ≤ 45 mg/m^2/day allowed provided it was received ≤ 5 days prior to study registration

Additional Information

Official title S0521, A Randomized Trial of Maintenance Versus Observation for Patients With Previously Untreated Low and Intermediate Risk Acute Promyelocytic Leukemia (APL), Phase III
Description OBJECTIVES: - Compare disease-free survival (DFS) among patients with previously untreated low and intermediate risk acute promyelocytic leukemia (APL) who are PCR-negative for Promyelocytic-retinoic acid receptor alpha (PML-RARα) after consolidation therapy and receive maintenance therapy versus patients who receive no maintenance therapy. (Randomization and observation arm closed as of 8/15/10) - Assess the toxicity of induction, consolidation and maintenance in these patients. - Test whether gene expression profiles assessed prior to treatment are predictive of resistance to remission induction chemotherapy and correlate with detectable minimal residual disease post-consolidation therapy. (Only one patient was not in molecular remission after receiving consolidation. Therefore, the predictive value of pre-treatment gene expression profiling could not be determined and is not reported here). - Investigate in a preliminarily manner the outcomes of patients who fail to achieve or maintain PCR-negative PML-RARα fusion gene after consolidation therapy when treated with gemtuzumab ozogamicin. (Only one patient was treated with gemtuzumab ozogamicin as part of protocol treatment. Therefore, results for this objective are not reported). OUTLINE: This is a randomized, multicenter study. - Induction therapy: Patients receive oral tretinoin twice daily until morphologic complete remission (CR) or for a maximum of 90 days in the absence of disease progression or unacceptable toxicity. Patients also receive cytarabine IV continuously on days 3-9 and daunorubicin hydrochloride IV on days 3-6. - Consolidation therapy: Patients who achieve CR, CR with incomplete blood count recovery (CRi), or partial remission (PR) after induction therapy receive arsenic trioxide IV over 2 hours 5 days a week for 5 weeks. After a 2-week rest period, patients receive a second course of arsenic trioxide. Within 14-30 days after blood count recovery, patients receive oral tretinoin twice daily on days 1-7 and daunorubicin hydrochloride IV on days 1-3. Patients receive a second course of tretinoin and daunorubicin hydrochloride after adequate blood count recovery. - Post-consolidation therapy: Patients who do not achieve molecular CR (CRm), but do achieve CR or CRi and are still PML-RARα-positive after consolidation therapy, receive gemtuzumab ozogamicin IV over 2 hours on days 1 and 15. Treatment repeats every 14 days for up to 6 courses or until PML-RARα-negative by PCR. (closed as of 8/15/10)Patients are stratified according to age (18 to 60 years vs > 60 years), acute promyelocytic leukemia (APL) risk group (low vs intermediate), and if the patient received consolidation therapy courses 3 or 4 (yes vs no) regardless of their CRm response. These patients are randomized to 1 of 2 treatment arms. (Randomization and observation arm closed as of 8/15/10) All patients are non-randomly assigned to receive post-consolidation therapy. - Arm I: Beginning 14-30 days after blood count recovery, patients receive oral tretinoin twice daily on days 1-7, oral mercaptopurine once daily on days 1-14, and oral methotrexate on day 1. Treatment repeats every 2 weeks for up to 1 year. - Arm II: Patients receive no further chemotherapy. Patients are followed every 3 months for 1 year. (Randomization and observation arm closed as of 8/15/10) Patients undergo blood collection periodically for cytogenetic studies. Samples are analyzed for PML-RARα fusion gene via reverse transcriptase-polymerase chain reaction (RT-PCR) assay and gene expression profiling. After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.
Trial information was received from ClinicalTrials.gov and was last updated in August 2015.
Information provided to ClinicalTrials.gov by Southwest Oncology Group.