Gemtuzumab Ozogamicin (GO) Monotherapy Versus Standard Supportive Care for Previously Untreated AML in Elderly Patients Who Are Not Eligible for Intensive Chemotherapy: A Randomized Phase II/III Trial (AML-19) of the EORTC-LG and GIMEMA-ALWP
61 Years
N/A
Both
Leukemia
Trial Information
Gemtuzumab Ozogamicin (GO) Monotherapy Versus Standard Supportive Care for Previously Untreated AML in Elderly Patients Who Are Not Eligible for Intensive Chemotherapy: A Randomized Phase II/III Trial (AML-19) of the EORTC-LG and GIMEMA-ALWP
OBJECTIVES:
- Compare the feasibility, toxicity, and antileukemic activity of two different dosing
regimens of gemtuzumab ozogamicin (GO) vs standard supportive care in older patients
with previously untreated acute myeloid leukemia who are not candidates for intensive
chemotherapy. (phase II)
- Compare the efficacy and toxicity of the best dosing regimen of GO selected from phase
II vs standard supportive care, in terms of overall survival, in these patients. (phase
III)
OUTLINE: This is a randomized, open-label, multicenter phase II study followed by a phase
III study. Patients are stratified according to age (61 to 75 vs 76 to 80 vs 81 and over),
CD33-positivity of bone marrow blasts (< 20% vs 20-80% vs > 80% vs unknown), initial WBC
before hydroxyurea administration (< 30,000/mm^3 vs ≥ 30,000/mm^3), WHO performance status
(0-1 vs 2 vs 3-4), and participating center.
- Phase II: Patients are randomized to 1 of 3 treatment arms.
- Arm I: Patients receive gemtuzumab ozogamicin (GO) IV over 2 hours on days 1 and
8. Patients with stable or responding disease at day 36 receive GO IV over 2 hours
every 4 weeks for up to 8 courses in the absence of disease progression or
unacceptable toxicity.
- Arm II: Patients receive GO IV over 2 hours on days 1, 3, and 5. Patients with
stable or responding disease at day 36 receive GO IV over 2 hours every 4 weeks
for up to 8 courses in the absence of disease progression or unacceptable
toxicity.
- Arm III: Patients receive standard supportive care.
- Phase III: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive the selected treatment (arm I or arm II) from phase II.
- Arm II: Patients receive standard supportive care. Patients who receive GO
treatment are followed monthly for 1 year and then every 3 months thereafter.
Patients who receive standard supportive care are followed at least every 4 weeks.
PROJECTED ACCRUAL: A total of 259 patients (75 for phase II [25 per treatment arm] and 184
for phase III [92 per treatment arm]) will be accrued for this study within 2.5 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed acute myeloid leukemia (AML)
- At least 20% bone marrow blasts by bone marrow aspiration or biopsy
- All subtypes except M3 (acute promyelocytic leukemia) are allowed
- Previously untreated primary or secondary disease (including AML after
myelodysplastic syndromes)
- Ineligible for intensive chemotherapy, as defined by 1 of the following criteria:
- 61 to 75 years old AND WHO performance status > 2 AND/OR unwilling to receive
intensive chemotherapy
- Over 75 years old
- No blast crisis of chronic myeloid leukemia
- No AML supervention after other myeloproliferative disease
- WBC < 30,000/mm^3 and meets 1 of the following criteria:
- WBC < 30,000/mm^3 at diagnosis AND had no prior treatment with hydroxyurea
- WBC ≥ 30,000/mm^3 at diagnosis AND received mandatory pretreatment with
hydroxyurea (up to 14 days duration) until WBC < 30,000/mm^3
- No active CNS leukemia
PATIENT CHARACTERISTICS:
Age
- See Disease Characteristics
- 61 and over
Performance status
- See Disease Characteristics
Life expectancy
- Not specified
Hematopoietic
- See Disease Characteristics
Hepatic
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
Renal
- Creatinine ≤ 1.5 times ULN
Cardiovascular
- No arrhythmia requiring chronic treatment
- No congestive heart failure
- No symptomatic ischemic heart disease
- No other severe cardiovascular disease
Pulmonary
- No severe pulmonary dysfunction ≥ grade 3
Other
- No alcohol abuse
- No severe neurological or psychiatric disease
- No active uncontrolled infection or severe systemic infection
- No other malignancy
- No psychological, familial, sociological, or geographical condition that would
preclude study compliance and follow-up
- HIV negative
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)
- No concurrent antiangiogenic drugs
Chemotherapy
- See Disease Characteristics
- Concurrent low-dose cytostatic agents (i.e., thioguanine or mercaptopurine) allowed
for palliative care (standard supportive care arm only)
Endocrine therapy
- Prior corticosteroids (duration ≤ 14 days ) for primary or secondary AML allowed
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- No other concurrent cytotoxic drugs
- No other concurrent experimental therapy
- No concurrent tyrosine kinase inhibitors
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Proportion of patients able to start continuation therapy (Phase II)
Safety Issue:
No
Principal Investigator
Sergio Amadori, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
EORTC - AZIENDA OSPEDALLERA UNIVERSITARIA - POLICLINICO TOR VERGATA, IT
Authority:
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Study ID:
EORTC-06031
NCT ID:
NCT00091234
Start Date:
June 2004
Completion Date:
Related Keywords:
- 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)
- untreated adult acute myeloid leukemia
- secondary acute myeloid leukemia
- adult acute basophilic leukemia
- adult acute eosinophilic leukemia
- adult erythroleukemia (M6a)
- adult pure erythroid leukemia (M6b)
- adult acute megakaryoblastic leukemia (M7)
- adult acute minimally differentiated myeloid leukemia (M0)
- adult acute monoblastic leukemia (M5a)
- adult acute monocytic leukemia (M5b)
- adult acute myeloblastic leukemia with maturation (M2)
- adult acute myeloblastic leukemia without maturation (M1)
- adult acute myelomonocytic leukemia (M4)
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
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