Cytarabine and Daunorubicin With or Without Gemtuzumab Ozogamicin in Treating Older Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

NCT ID: NCT00121303

Last Updated: 2016-09-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 600 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2016-06-30

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cytarabine and daunorubicin, 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 ozogamicin, 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. It is not yet known whether cytarabine and daunorubicin followed by gemtuzumab ozogamicin is more effective than cytarabine and daunorubicin in treating acute myeloid leukemia or myelodysplastic syndromes.

PURPOSE: This randomized phase III trial is studying cytarabine and two different doses of daunorubicin to see how well they work compared to cytarabine and daunorubicin followed by gemtuzumab ozogamicin in treating older patients with acute myeloid leukemia or myelodysplastic syndromes.

Detailed Description

OBJECTIVES:

Primary

• Compare the event-free and disease-free survival of older patients with acute myeloid leukemia, refractory anemia with excess blasts (RAEB), or RAEB in transformation treated with induction therapy comprising cytarabine in combination with two different doses of daunorubicin followed by cytarabine alone with or without post-induction therapy comprising gemtuzumab ozogamicin.

Secondary

• Compare the complete remission rate in patients treated with these regimens.
• Compare the overall survival of patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Determine the probability of relapse and death during first complete remission in patients treated with post-induction gemtuzumab ozogamicin.
• Correlate prognostic factors (e.g., CD33 positivity, multidrug resistance phenotype, or cytogenetics) with probability of complete remission and overall, event-free, and disease-free survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and diagnosis (acute myeloid leukemia [AML] vs myelodysplastic syndromes [MDS]) for induction therapy. Patients are stratified according to participating center, diagnosis (AML vs MDS), induction treatment arm (I vs II), and response to induction therapy (complete remission [CR] vs no CR) for post-induction therapy.

• Induction therapy (course 1): Patients are randomized to 1 of 2 induction treatment arms.

• Arm I: Patients receive cytarabine IV continuously on days 1-7 and daunorubicin IV over 3 hours on days 1-3.
• Arm II: Patients receive cytarabine as in arm I and daunorubicin as in arm I but at a higher dose.

Approximately 28-35 days after the start of course 1 (or sooner if the bone marrow shows evidence of resistant disease), patients in both arms proceed to course 2 of induction therapy.

• Induction therapy (course 2): All patients receive cytarabine IV over 6 hours twice daily on days 1-6.

After completion of course 2, patients undergo assessment of remission status. Patients who do not achieve CR are removed from the study. Patients achieving CR proceed to post-induction therapy and undergo a second randomization.

• Post-induction therapy: Patients are randomized to 1 of 2 post-induction treatment arms.

• Arm I: Patients receive no further chemotherapy.
• Arm II: Patients receive gemtuzumab ozogamicin IV over 2 hours on days 1, 29, and 57 in the absence of disease relapse or unacceptable toxicity.

After completion of study treatment, patients are followed monthly for 1 year, every 3 months for 2 years, every 4-6 months for 2 years, and then periodically thereafter.

PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study within 4-5 years.

Conditions

Leukemia; Myelodysplastic Syndromes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A low dose Dauno

Induction 45 mg Dauno

Group Type: ACTIVE_COMPARATOR

cytarabine

Intervention Type: DRUG

daunorubicin hydrochloride

Intervention Type: DRUG

ARM B high dose Dauno

Induction 90 mg Dauno

Group Type: EXPERIMENTAL

cytarabine

Intervention Type: DRUG

daunorubicin hydrochloride

Intervention Type: DRUG

Arm 1 no further treatment

Group Type: NO_INTERVENTION

No interventions assigned to this group

Arm 2 Mylotarg

Post induction treatment with Mylotarg

Group Type: EXPERIMENTAL

gemtuzumab ozogamicin

Intervention Type: DRUG

Interventions

cytarabine

Intervention Type: DRUG

daunorubicin hydrochloride

Intervention Type: DRUG

gemtuzumab ozogamicin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Refractory anemia with excess blasts (RAEB) or RAEB in transformation

• International Prognostic Scoring System score ≥ 1.5 NOTE: *Any prior hematological disease of ≥ 4 months duration
• No chronic myelogenous leukemia in blastic crisis
• No prior polycythemia rubra vera
• No primary myelofibrosis

PATIENT CHARACTERISTICS:

Age

• 61 and over

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• ALT and/or AST ≤ 2.5 times upper limit of normal (ULN)*
• Bilirubin ≤ 2 times ULN* NOTE: *Unless elevation is caused by organ infiltration by AML

Renal

• Creatinine ≤ 2 times ULN* NOTE: *Unless elevation is caused by organ infiltration by AML

Cardiovascular

• No myocardial infarction within the past 6 months
• LVEF > 50% by MUGA, echocardiogram, or other methods
• No unstable angina
• No unstable cardiac arrhythmia
• No severe and/or uncontrolled hypertension

Other

• No uncontrolled diabetes
• No severe and/or uncontrolled infection
• No other severe and/or uncontrolled medical condition

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• More than 6 months since prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No prior induction therapy for AML or myelodysplastic syndromes

• Minimum Eligible Age: 61 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stichting Hemato-Oncologie voor Volwassenen Nederland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonathan Kell, MRCPath

Role: STUDY_CHAIR

University Hospital of Wales

Locations

North Hampshire Hospital

Basingstoke, England, United Kingdom

Kent and Canterbury Hospital

Canterbury, England, United Kingdom

Medway Maritime Hospital

Gillingham Kent, England, United Kingdom

Maidstone Hospital

Maidstone, England, United Kingdom

Royal Cornwall Hospital

Truro, Cornwall, England, United Kingdom

University Hospital of Wales

Cardiff, Wales, United Kingdom

Countries

United Kingdom

Other Identifiers

SAKK-AML-43

Identifier Type: -

Identifier Source: secondary_id

EU-20514

Identifier Type: -

Identifier Source: secondary_id

HOVON-AML-43

Identifier Type: -

Identifier Source: secondary_id

CDR0000433422

Identifier Type: -

Identifier Source: org_study_id