S0106 Cytarabine and Daunorubicin w/ or w/o Gemtuzumab Followed By HD Cytarabine and Either Gemtuzumab or Nothing in de Novo AML
- Conditions
- Leukemia
- Interventions
- Registration Number
- NCT00085709
- Lead Sponsor
- SWOG Cancer Research Network
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as cytarabine and daunorubicin, work in different ways to stop cancer cells from dividing so they stop growing and die. Monoclonal antibodies, such as gemtuzumab ozogamicin, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining chemotherapy with gemtuzumab ozogamicin may kill more cancer cells. It is not yet known whether induction therapy using cytarabine and daunorubicin is more effective with or without gemtuzumab ozogamicin or whether postconsolidation therapy using gemtuzumab ozogamicin is more effective than no additional therapy in treating de novo (first occurrence) acute myeloid leukemia.
PURPOSE: This randomized phase III trial is comparing two different regimens of chemotherapy and monoclonal antibody therapy to see how well they work in treating patients with previously untreated de novo acute myeloid leukemia.
- Detailed Description
OBJECTIVES:
* Compare disease-free survival of patients with previously untreated de novo acute myeloid leukemia treated with induction therapy comprising cytarabine and daunorubicin with vs without gemtuzumab ozogamicin followed by consolidation therapy comprising high-dose cytarabine and post-consolidation therapy comprising gemtuzumab ozogamicin vs no additional therapy.
* Compare the complete remission rate in patients treated with these regimens.
* Compare the frequency and severity of the toxic effects of these regimens in these patients.
Other objectives (if funding allows):
* Determine the prognostic significance of CD33 expression on the response rate in patients receiving gemtuzumab ozogamicin.
* Determine the prognostic significance of FLT3 mutations in these patients before treatment with these regimens.
* Determine the prognostic significance of minimal residual disease in remission specimens from these patients treated with these regimens.
* Determine the prognostic significance of the flow cytometric detection of minimal residual disease in specimens collected from these patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified during induction therapy according to age (\< 35 years vs ≥ 35 years) and during post-consolidation therapy according to preinduction cytogenetic risk group.
* Induction therapy: Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive daunorubicin IV on days 1-3, cytarabine IV continuously on days 1-7, and gemtuzumab ozogamicin IV over 2 hours on day 4. Patients receive filgrastim (G-CSF) or sargramostim (GM-CSF) IV or subcutaneously once daily beginning on day 15 and continuing until blood counts recover.
* Arm II: Patients receive daunorubicin, cytarabine, and G-CSF or GM-CSF as in arm I.
Patients in both arms undergo bone marrow aspiration and biopsy on day 14 (and on day 19, if applicable) and then proceed to reinduction therapy.
* Reinduction therapy: Patients receive daunorubicin IV on days 1-3 and cytarabine IV continuously on days 1-7. Patients also receive G-CSF or GM-CSF as in induction therapy.
Patients who achieve A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status proceed to consolidation therapy.
* Consolidation therapy: Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1, 3, and 5. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Patients who maintain A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status after consolidation therapy proceed to post-consolidation therapy.
* Post-consolidation therapy: Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive gemtuzumab ozogamicin IV over 2 hours on day 1. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive no additional therapy. Patients are observed at days 30 and 60 after randomization.
Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.
PROJECTED ACCRUAL: A total of 684 patients (342 per treatment arm) will be accrued for this study within 4.5-5 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 637
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Post-consolidation observation observation Patients receive no additional therapy. Patients are observed at days 30 and 60 after randomization. Induction 7+3 Cytosine arabinoside Standard induction regimen of 7 days of Ara-C (cytosine arabinoside) and 3 days of daunomycin Post-consolidation GO gemtuzumab ozogamicin Patients receive gemtuzumab ozogamicin IV over 2 hours on day 1. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. Induction 7+3 Daunomycin Standard induction regimen of 7 days of Ara-C (cytosine arabinoside) and 3 days of daunomycin Induction 7+3+GO Cytosine arabinoside Gemtuzumab (GO) added to the standard induction regimen of 7 days of Ara-C and 3 days of daunomycin Induction 7+3+GO Daunomycin Gemtuzumab (GO) added to the standard induction regimen of 7 days of Ara-C and 3 days of daunomycin
- Primary Outcome Measures
Name Time Method 2-year Disease-free Survival (DFS) After completing any treatment, every 6 months for 2 years, than annually for years 3-5 Measured from data of randomization to post-consolidation therapy until relapse from complete response or death from any cause, with observations censored at the date of last contact for patients last known to be alive without report of relapse.
Complete Remission After induction therapy was completed (1 or 2 months)
- Secondary Outcome Measures
Name Time Method Toxicity For induction, daily for the first 10 days, then twice weekly until consolidation treatment. Weekly during consolidation treatment. Weekly if randomized to post-consolidation G.O. Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event
Related Research Topics
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Trial Locations
- Locations (277)
Providence Cancer Center
🇺🇸Anchorage, Alaska, United States
Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
🇺🇸Ft. Smith, Arkansas, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Alta Bates Summit Comprehensive Cancer Center
🇺🇸Berkeley, California, United States
Peninsula Medical Center
🇺🇸Burlingame, California, United States
Marin Cancer Institute at Marin General Hospital
🇺🇸Greenbrae, California, United States
Sutter Health - Western Division Cancer Research Group
🇺🇸Greenbrae, California, United States
USC/Norris Comprehensive Cancer Center and Hospital
🇺🇸Los Angeles, California, United States
California Pacific Medical Center - California Campus
🇺🇸San Francisco, California, United States
Sutter Solano Medical Center
🇺🇸Vallejo, California, United States
Scroll for more (267 remaining)Providence Cancer Center🇺🇸Anchorage, Alaska, United States