Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Cytarabine and Daunorubicin With or Without Gemtuzumab Ozogamicin Followed By High-Dose Cytarabine Followed By Either Gemtuzumab Ozogamicin or No Additional Therapy in Treating Patients With Previously Untreated De Novo Acute Myeloid Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 to 60	NCI	SWOG-S0106 S0106, NCT00085709

Special Category: CTSU trial, NCI Web site featured trial

Objectives

1. 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.
2. Compare the complete remission rate in patients treated with these regimens.
3. Compare the frequency and severity of the toxic effects of these regimens in these patients.
4. Determine the prognostic significance of CD33 expression on the response rate in patients receiving gemtuzumab ozogamicin.
5. Determine the prognostic significance of FLT3 mutations in these patients before treatment with these regimens.
6. Determine the prognostic significance of minimal residual disease in remission specimens from these patients treated with these regimens.
7. Determine the prognostic significance of the flow cytometric detection of minimal residual disease in specimens collected from these patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Morphologically confirmed acute myeloid leukemia (AML) by bone marrow aspiration and biopsy* within the past 14 days
  • No M3 disease

   [Note: *Patients with marked leukocytosis may be registered before the availability of biopsy results if the absolute blast count is ≥ 100,000 cells/µL]

• No blastic transformation of chronic myelogenous leukemia
• No pre-existing hematologic disorder evolving to AML (e.g., myelodysplasia or secondary leukemia)

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• No prior systemic chemotherapy
  • Prior hydroxyurea to control high cell counts allowed
• No more than 1 prior dose of intrathecal chemotherapy for acute leukemia
• Concurrent intrathecal chemotherapy allowed during induction therapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Patient Characteristics:

Age

• 18 to 60

Performance status

• Zubrod 0-3

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN
• No known hepatitis B or C infection
• No known liver disease

Renal

• Not specified

Cardiovascular

• LVEF ≥ 50% by MUGA or echocardiogram
• No unstable cardiac arrhythmias
• No unstable angina

Other

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission
• Not pregnant or nursing
• Fertile patients must use effective contraception

Expected Enrollment

A total of 684 patients (342 per treatment arm) will be accrued for this study within 4.5-5 years.

Outcomes

Disease-free survival
Induction complete remission rate

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.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Stephen Petersdorf, MD, Study coordinator		Ph: 206-288-2036

Related Information

Featured trial article

Registry Information
Official Title		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)
Trial Start Date		2004-07-22
Trial Completion Date		2010-03-01 (estimated)
Registered in ClinicalTrials.gov		NCT00085709
Date Submitted to PDQ		2004-03-02
Information Last Verified		2009-08-22
NCI Grant/Contract Number		CA32102

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