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

Sponsor:	European Organization for Research and Treatment of Cancer
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00077116

Purpose

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	Intervention	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 II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control
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

Resource links provided by NLM:

MedlinePlus related topics: Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Cyclophosphamide Busulfan Cytarabine hydrochloride Idarubicin hydrochloride Idarubicin Gemtuzumab ozogamicin Cytarabine

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

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 [ Designated as safety issue: No ]
Severe toxicity after the start of treatment [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Disease-free survival from CR/CRp [ Designated as safety issue: No ]
Duration of overall survival [ Designated as safety issue: No ]
Severity of pancytopenia and duration of recovery in patients who reached CR/CRp after the start of treatment [ Designated as safety issue: No ]

Estimated Enrollment:	28
Study Start Date:	November 2003

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.

Eligibility

Ages Eligible for Study:	16 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00077116

Locations

Belgium
AZ Sint-Jan
Brugge, Belgium, 8000
Cliniques Universitaires Saint-Luc
Brussels, Belgium, 1200
H. Hartziekenhuis - Roeselaere.
Roeselare, Belgium, 8800
Institut Jules Bordet
Brussels, Belgium, 1000
Germany
Ruprecht - Karls - Universitaet Heidelberg
Heidelberg, Germany, D-69117
Netherlands
Leiden University Medical Center
Leiden, Netherlands, 2300 CA
Onze Lieve Vrouwe Gasthuis
Amsterdam, Netherlands, 1091 HA
Universitair Medisch Centrum St. Radboud - Nijmegen
Nijmegen, Netherlands, NL-6500 HB
Switzerland
Universitaetsspital-Basel
Basel, Switzerland, CH-4031

Sponsors and Collaborators

European Organization for Research and Treatment of Cancer

Investigators

Investigator:

Theo De Witte, MD, PhD

Universitair Medisch Centrum St. Radboud - Nijmegen

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000349501, EORTC-06013
Study First Received:	February 10, 2004
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00077116 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Precancerous Conditions
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Antibiotics, Antineoplastic
Leukemia, Myeloid, Acute
Antibodies, Monoclonal
Leukemia
Preleukemia
Pathologic Processes

Syndrome
Therapeutic Uses
Alkylating Agents
Cytarabine
Disease
Neoplasms by Histologic Type
Hematologic Diseases
Myelodysplastic Syndromes
Leukemia, Myeloid
Gemtuzumab
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Idarubicin

ClinicalTrials.gov processed this record on November 27, 2009