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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)


Phase 3
61 Years
N/A
Open (Enrolling)
Both
Leukemia, Myelodysplastic Syndromes

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Trial Information

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)


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.

Inclusion Criteria


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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Event-free survival after induction therapy

Safety Issue:

No

Principal Investigator

Jonathan Kell, MRCPath

Investigator Role:

Study Chair

Investigator Affiliation:

The University of New South Wales

Authority:

Netherlands: Independent Ethics Committee

Study ID:

CDR0000433422

NCT ID:

NCT00121303

Start Date:

January 2005

Completion Date:

Related Keywords:

  • Leukemia
  • Myelodysplastic Syndromes
  • adult acute monocytic leukemia (M5b)
  • adult erythroleukemia (M6a)
  • adult pure erythroid leukemia (M6b)
  • adult acute megakaryoblastic leukemia (M7)
  • adult acute myeloblastic leukemia with maturation (M2)
  • adult acute myeloblastic leukemia without maturation (M1)
  • adult acute myelomonocytic leukemia (M4)
  • adult acute monoblastic leukemia (M5a)
  • refractory anemia with excess blasts in transformation
  • refractory anemia with excess blasts
  • secondary acute myeloid leukemia
  • untreated adult acute myeloid leukemia
  • de novo myelodysplastic syndromes
  • adult acute minimally differentiated myeloid leukemia (M0)
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with t(8;21)(q22;q22)
  • secondary myelodysplastic syndromes
  • Anemia, Refractory
  • Anemia, Refractory, with Excess of Blasts
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia

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