Overview

This trial is active, not recruiting.

Conditions leukemia, myelodysplastic syndromes
Treatments cytarabine, daunorubicin hydrochloride, gemtuzumab ozogamicin
Phase phase 3
Sponsor Stichting Hemato-Oncologie voor Volwassenen Nederland
Start date January 2005
End date January 2009
Trial size 600 participants
Trial identifier NCT00121303, CDR0000433422, EU-20514, HOVON-AML-43, SAKK-AML-43

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Induction 45 mg Dauno
cytarabine
daunorubicin hydrochloride
(Experimental)
Induction 90 mg Dauno
cytarabine
daunorubicin hydrochloride
(No Intervention)
(Experimental)
Post induction treatment with Mylotarg
gemtuzumab ozogamicin

Primary Outcomes

Measure
Event-free survival after induction therapy
time frame:
Disease-free survival after maintenance therapy
time frame:

Secondary Outcomes

Measure
Complete remission (CR) rate after induction therapy
time frame:
Overall survival after induction therapy
time frame:
Toxicity after induction therapy
time frame:
Toxicity after maintenance therapy
time frame:
Probability of relapse and death in first CR after maintenance therapy
time frame:
Overall survival after maintenance therapy
time frame:

Eligibility Criteria

Male or female participants at least 61 years old.

DISEASE CHARACTERISTICS: - Histologically or cytologically confirmed diagnosis of 1 of the following: - Acute myeloid leukemia (AML) - M0-M2 or M4-M7 FAB subtype - No AML with cytogenetic abnormality t(15;17) (M3) - Patients with secondary AML progressing from prior myelodysplasia* or biphenotypic leukemia are eligible - 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

Additional Information

Official title Randomised Induction and Post Induction Therapy in Older Patients (≥61 Years of Age) With Acute Myeloid Leukemia (AML) and Refractory Anemia With Excess Blasts (RAEB, RAEB-t)
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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by Stichting Hemato-Oncologie voor Volwassenen Nederland.