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

Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00121303
• Other study ID #: CDR0000433422
• Secondary ID: SAKK-AML-43EU-20
• Status: Completed
• Phase: Phase 3
• First received: July 19, 2005
• Last updated: September 19, 2016
• Start date: January 2005
• Est. completion date: June 2016

Study information

• Verified date: September 2016
• Source: Stichting Hemato-Oncologie voor Volwassenen Nederland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Independent Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 600
• Est. completion date: June 2016
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 61 Years to 120 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia, Refractory, with Excess of Blasts
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• cytarabine

• daunorubicin hydrochloride

• gemtuzumab ozogamicin

Locations

Country	Name	City	State
United Kingdom	North Hampshire Hospital	Basingstoke	England
United Kingdom	Kent and Canterbury Hospital	Canterbury	England
United Kingdom	University Hospital of Wales	Cardiff	Wales
United Kingdom	Medway Maritime Hospital	Gillingham Kent	England
United Kingdom	Maidstone Hospital	Maidstone	England
United Kingdom	Royal Cornwall Hospital	Truro, Cornwall	England

Sponsors (1)

Lead Sponsor	Collaborator
Stichting Hemato-Oncologie voor Volwassenen Nederland

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival after induction therapy			No
Primary	Disease-free survival after maintenance therapy			No
Secondary	Complete remission (CR) rate after induction therapy			No
Secondary	Overall survival after induction therapy			No
Secondary	Toxicity after induction therapy			Yes
Secondary	Toxicity after maintenance therapy			Yes
Secondary	Probability of relapse and death in first CR after maintenance therapy			No
Secondary	Overall survival after maintenance therapy			No