NCT00085709

S0106 Cytarabine and Daunorubicin w/ or w/o Gemtuzumab Followed By HD Cytarabine and Either Gemtuzumab or Nothing in de Novo AML

A Phase III Study of the Addition of Gemtuzumab Ozogamicin (Mylotarg®) During Induction Therapy Versus Standard Induction With Daunomycin and Cytosine Arabinoside Followed by Consolidation and Subsequent Randomization to Post-Consolidation Therapy With Gemtuzumab Ozogamicin (Mylotarg®) or No Additional Therapy For Patients Under Age 61 With Previously Untreated De Novo Acute Myeloid Leukemia (AML)

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 637 (actual)
• Sponsor: SWOG Cancer Research Network · Network
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Leukemia

Interventions

Type	Name	Description
DRUG	gemtuzumab ozogamicin	Given IV, induction Arm1 6mg/m2 D4; post-consolidation 5mg/m2 3 doses \>/= 28 days apart
OTHER	observation	No treatment given
DRUG	Cytosine arabinoside	IV; induction Arms1/2 and reinduction 100 mg/m2/d days 1-7; consolidation 3gm/m2 q3hrs D1, 3, 5
DRUG	Daunomycin	IV; induction Arm1 45mg/m2 D1-3; Arm2 and reinduction 60 mg/m2 D1-3;

Timeline

• Start date: 2004-07-01
• Primary completion: 2010-03-01
• Completion: 2014-08-01
• First posted: 2004-06-16
• Last updated: 2015-09-30
• Results posted: 2012-08-27

Locations

279 sites across 3 countries: United States, Canada, Sweden