Idarubicin and Ara-C in Combination With Gemtuzumab-Ozogamicin (IAGO) for Young Untreated Patients, Without an HLA Identical Sibling, With High Risk MDS or AML Developing After a Preceding Period With MDS During 6 Months Duration: A Phase II Study
16 Years
70 Years
Both
Leukemia, Myelodysplastic Syndromes
Trial Information
Idarubicin and Ara-C in Combination With Gemtuzumab-Ozogamicin (IAGO) for Young Untreated Patients, Without an HLA Identical Sibling, With High Risk MDS or AML Developing After a Preceding Period With MDS During 6 Months Duration: A Phase II Study
OBJECTIVES:
Primary
- Determine the feasibility of combining gemtuzumab ozogamicin with idarubicin and
cytarabine with or without cyclophosphamide with total body irradiation vs busulfan
followed by allogeneic stem cell transplantation in patients with previously untreated
high-risk myelodysplastic syndromes (MDS) or acute myeloid leukemia secondary to MDS.
- Determine the toxicity profile of this regimen in these patients.
- Determine the antileukemic/anti-MDS activity of this regimen in these patients.
Secondary
- Determine the hepatotoxicity of this regimen, in terms of veno-occlusive disease, in
these patients.
- Determine the severity of pancytopenia and duration of recovery in patients treated
with this regimen.
OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 treatment groups.
- Group 1 (for patients with no HLA-matched sibling donor): Patients receive
remission-induction chemotherapy comprising idarubicin IV over 5 minutes on days 1, 3,
and 5; cytarabine IV continuously over 24 hours on days 1-10; and gemtuzumab ozogamicin
IV over 2 hours on day 7. Treatment continues for a second course in the absence of
unacceptable toxicity.
- Group 2 (for patients with an HLA-matched sibling donor): Patients are randomized to 1
of 2 treatment arms.
- Arm I: Patients receive myeloablative consolidation chemotherapy comprising
cyclophosphamide on days -6 and -5 and total body irradiation twice daily on days
-4 to -2.
- Arm II: Patients receive myeloablative consolidation chemotherapy comprising
busulfan on days -8 to -5 and cyclophosphamide on days -4 and -3.
Patients in both arms may alternatively undergo T-cell depletion and/or a reduced-intensity
conditioning regimen.
Approximately 4-8 weeks after completion of consolidation chemotherapy, all patients in
group 2 undergo allogeneic bone marrow transplantation or allogeneic peripheral blood stem
cell transplantation. Patients in group 2 then proceed to remission-induction chemotherapy
as in group 1.
Patients achieving complete remission are recommended for consolidation therapy off study.
Patients are followed monthly for 6 months, every 2 months for 6 months, and then every 3
months thereafter.
PROJECTED ACCRUAL: A total of 28 patients will be accrued for this study within 10 months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed diagnosis of 1 of the following:
- High-risk myelodysplastic syndromes (MDS), including any of the following:
- Refractory anemia with excess blasts (RAEB) with > 10% blast cells in the
bone marrow
- RAEB in transformation
- Other forms of MDS with multiple (3 or more) chromosomal abnormalities or
chromosome 7 abnormalities AND/OR profound cytopenias, defined as
neutrophil count < 500/mm^3 and/or platelet count < 20,000/mm^3
- Chronic myelomonocytic leukemia with > 5% blast cells in the bone marrow
- Chronic myelomonocytic leukemia with neutrophil count > 16,000/mm^3 OR
monocyte count > 2,600/mm^3
- Secondary acute myeloid leukemia supervening after overt MDS of more than 6
months in duration
- Patients with or without an HLA-identical sibling
- No active CNS leukemia
PATIENT CHARACTERISTICS:
Age
- 16 to 70
Performance status
- WHO 0-2
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 severe cardiovascular disease
- No arrhythmias requiring chronic treatment
- No congestive heart failure
- No symptomatic ischemic heart disease
Pulmonary
- No severe lung disease
Other
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No HIV positivity
- No other concurrent malignant disease
- No active uncontrolled infection
- No history of alcohol abuse (i.e., averaged less than 5 alcoholic consumptions daily
for the past year)
- No concurrent severe neurological or psychiatric disease
- No other psychological, familial, sociological, or geographical condition that would
preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- More than 6 weeks since prior growth factors
Chemotherapy
- No prior intensive chemotherapy
- More than 6 weeks since prior low-dose chemotherapy or hydroxyurea
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- More than 6 weeks since prior immunosuppressants
- No prior participation in this clinical study
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Rate of complete remission (CR) or complete remission with incomplete recovery of platelets (CRp) as measured by Cheson response criteria after the start of treatment
Safety Issue:
No
Principal Investigator
Theo De Witte, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
Universitair Medisch Centrum St. Radboud - Nijmegen
Authority:
United States: Federal Government
Study ID:
EORTC-06013
NCT ID:
NCT00077116
Start Date:
November 2003
Completion Date:
Related Keywords:
- Leukemia
- Myelodysplastic Syndromes
- untreated adult acute myeloid leukemia
- refractory anemia with excess blasts
- refractory anemia with excess blasts in transformation
- chronic myelomonocytic leukemia
- de novo myelodysplastic syndromes
- secondary myelodysplastic syndromes
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- childhood myelodysplastic syndromes
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
- Myelodysplastic Syndromes
- Preleukemia
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