Idarubicin, Cytarabine, and Gemtuzumab Ozogamicin in Treating Patients With Previously Untreated High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia Secondary to Myelodysplastic Syndrome

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Completed

CT.gov ID

NCT00077116

Collaborator

(none)

Enrollment

Locations

3.4

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as gemtuzumab ozogamicin, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Giving monoclonal antibody therapy together with chemotherapy may kill more cancer cells. Giving healthy stem cells from a donor whose blood closely resembles the patient's blood will help the patient's bone marrow make new stem cells that become red blood cells, white blood cells, and platelets.

PURPOSE: This phase II trial is studying how well giving idarubicin and cytarabine together with gemtuzumab ozogamicin works in treating patients with previously untreated high-risk myelodysplastic syndrome or acute myeloid leukemia secondary to myelodysplastic syndrome.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Myelodysplastic Syndromes	Drug: busulfan Drug: cyclophosphamide Drug: cytarabine Drug: gemtuzumab ozogamicin Drug: idarubicin Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

31 participants

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2003

Actual Primary Completion Date :

Nov 1, 2006

Outcome Measures

Primary Outcome Measures

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 []
Severe toxicity after the start of treatment []

Secondary Outcome Measures

Disease-free survival from CR/CRp []
Duration of overall survival []
Severity of pancytopenia and duration of recovery in patients who reached CR/CRp after the start of treatment []

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	AZ Sint-Jan	Brugge	Belgium	8000
2	Institut Jules Bordet	Brussels	Belgium	1000
3	Cliniques Universitaires Saint-Luc	Brussels	Belgium	1200
4	H. Hartziekenhuis - Roeselaere.	Roeselare	Belgium	8800
5	Ruprecht - Karls - Universitaet Heidelberg	Heidelberg	Germany	D-69117
6	Onze Lieve Vrouwe Gasthuis	Amsterdam	Netherlands	1091 HA
7	Leiden University Medical Center	Leiden	Netherlands	2300 CA
8	Universitair Medisch Centrum St. Radboud - Nijmegen	Nijmegen	Netherlands	NL-6500 HB
9	Universitaetsspital-Basel	Basel	Switzerland	CH-4031