Chemotherapy With or Without Gemtuzumab Ozogamicin in Treating Older Patients With Acute Myeloid Leukemia (AML-17)

This study has been completed.
Sponsor:
Collaborator:
Gruppo Italiano Malattie EMatologiche dell'Adulto
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00052299
First received: January 24, 2003
Last updated: August 24, 2012
Last verified: August 2012
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known if combining combination chemotherapy with monoclonal antibody therapy will kill more cancer cells.

PURPOSE: Randomized phase III trial to determine the effectiveness of combination chemotherapy with or without gemtuzumab ozogamicin in treating patients who have acute myeloid leukemia.


Condition Intervention Phase
Leukemia
Drug: cytarabine
Drug: etoposide
Drug: gemtuzumab ozogamicin
Drug: idarubicin
Drug: mitoxantrone hydrochloride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Gemtuzumab Ozogamicin (GO) Combined With Standard Intensive Chemotherapy Versus Standard Intensive Chemotherapy Alone For Induction/Consolidation In Patients 61-75 Years Old With Previously Untreated AML: A Randomized Phase III Trial (AML-17) Of The EORTC-LG and the GIMEMA-ALWP

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response (complete remission [CR] or complete remission with incomplete recovery of platelet count [CRp]) rate after induction [ Designated as safety issue: No ]
  • Disease-free survival after CR/CRp [ Designated as safety issue: No ]
  • Incidence of relapse after CR/CRp [ Designated as safety issue: No ]
  • Incidence of death without relapse after CR/CRp [ Designated as safety issue: No ]
  • Event-free survival [ Designated as safety issue: No ]
  • Toxicity (highest grade) assessed by International Working Group CTC v2.0 [ Designated as safety issue: Yes ]

Enrollment: 472
Study Start Date: September 2002
Study Completion Date: February 2012
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ARM A
GO + MICE for remission induction followed by GO + mini-ICE for consolidation
Drug: cytarabine Drug: etoposide Drug: gemtuzumab ozogamicin Drug: idarubicin Drug: mitoxantrone hydrochloride
Active Comparator: ARM B
MICE for remission induction followed by mini-ICE for consolidation
Drug: cytarabine Drug: etoposide Drug: idarubicin Drug: mitoxantrone hydrochloride

Detailed Description:

OBJECTIVES:

  • Determine the antileukemic activity of standard induction chemotherapy with or without gemtuzumab ozogamicin in elderly patients with previously untreated acute myeloid leukemia.
  • Determine the overall survival of patients treated with these regimens.
  • Determine the rate of response, disease-free survival, event-free survival, incidence of relapse, and incidence of death of patients treated with these regimens.
  • Determine the rate, type, and grade of toxicity of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to age (61-69 vs 70-75), CD33 positivity (less than 5% vs 5-19% vs 20-80% vs more than 80% vs unknown), initial WBC before hydroxyurea administration if needed (less than 30,000/mm^3 vs at least 30,000/mm^3), and participating center. Patients are randomized to 1 of 2 treatment arms.

  • Arm I:

    • Induction (phase I): Patients receive gemtuzumab ozogamicin IV over 2 hours on days 1 and 15.
    • Induction (phase II/MICE regimen): Beginning between days 50 and 53, patients receive mitoxantrone IV over 30 minutes on days 1, 3, and 5; etoposide IV over 1 hour on days 1-3; and cytarabine IV continuously on days 1-7. Bone marrow evaluation is performed on day 29. Patients with partial remission (PR) receive a second course of MICE chemotherapy regimen. Patients with complete remission (CR) after 1 or 2 courses of MICE regimen proceed to consolidation therapy. Patients with progressive disease go off therapy.
    • Consolidation: Beginning within 4 weeks of documentation of CR, patients receive gemtuzumab ozogamicin IV over 2 hours on day 0; idarubicin IV on days 1, 3, and 5; etoposide IV over 1 hour on days 1-3; and cytarabine IV continuously on days 1-5. After at least day 30, patients receive a second consolidation course in the absence of disease progression or unacceptable toxicity.
  • Arm II:

    • Induction (MICE regimen): Patients receive mitoxantrone, etoposide, and cytarabine as in arm I induction. Bone marrow evaluation is performed on day 29. Patients with PR receive a second course of MICE chemotherapy regimen. Patients with CR after 1 or 2 courses of MICE regimen proceed to consolidation therapy. Patients with progressive disease go off therapy.
    • Consolidation: Patients receive idarubicin, etoposide, and cytarabine as in arm I consolidation.

Patients are followed monthly for 1 year, every 3 months for 2 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 450 patients (225 per treatment arm) will be accrued for this study within 3.75 years.

  Eligibility

Ages Eligible for Study:   61 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of acute myeloid leukemia (AML)

    • Bone marrow blasts at least 20% by bone marrow aspiration or biopsy
    • FAB subtypes M0-M2 and M4-M7

      • No acute promyelocytic leukemia (FAB subtype M3)
  • Previously untreated primary or secondary AML, including AML after myelodysplastic syndromes

    • Hydroxyurea and/or corticosteroid therapy for no more than 14 days allowed
  • No blast crisis of chronic myelogenous leukemia
  • No AML supervening after other myeloproliferative diseases
  • No active CNS leukemia

PATIENT CHARACTERISTICS:

Age

  • 61 to 75

Performance status

  • WHO 0-2

Life expectancy

  • Not specified

Hematopoietic

  • WBC less than 30,000/mm^3 (pretreatment with hydroxyurea for no more than 14 days allowed)

Hepatic

  • Bilirubin no greater than 3 times upper limit of normal (ULN)

Renal

  • Creatinine no greater than 3 times ULN

Cardiovascular

  • No concurrent severe cardiovascular disease
  • No arrhythmias requiring chronic treatment
  • No congestive heart failure
  • No symptomatic ischemic heart disease

Pulmonary

  • No severe pulmonary dysfunction (CTC grade 3-4)

Other

  • HIV negative
  • No other uncontrolled infection
  • No other concurrent malignant disease
  • No severe concurrent neurological or psychiatric disease
  • No prior alcohol abuse
  • No psychological, familial, sociological, or geographical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent hematopoietic growth factors (filgrastim [G-CSF] or sargramostim [GM-CSF]) except for life-threatening infection due to neutropenia

Chemotherapy

  • See Disease Characteristics

Endocrine therapy

  • See Disease Characteristics

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • No prior enrollment in this trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00052299

  Show 55 Study Locations
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Gruppo Italiano Malattie EMatologiche dell'Adulto
Investigators
Study Chair: Sergio Amadori, MD Azienda Ospedallera Universitaria - Policlinico Tor Vergata, Roma
  More Information

Additional Information:
No publications provided by European Organisation for Research and Treatment of Cancer - EORTC

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00052299     History of Changes
Other Study ID Numbers: EORTC-06012, EORTC-06012, AML-17, GIMEMA-AML-17
Study First Received: January 24, 2003
Last Updated: August 24, 2012
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
adult acute monocytic leukemia (M5b)
adult acute erythroid leukemia (M6)
adult acute megakaryoblastic leukemia (M7)
adult acute minimally differentiated myeloid leukemia (M0)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
untreated adult acute myeloid leukemia
secondary acute myeloid leukemia
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)

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Gemtuzumab
Mitoxantrone
Analgesics
Antineoplastic Agents
Central Nervous System Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014