Cytarabine and Daunorubicin With or Without Gemtuzumab Ozogamicin in Treating Older Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

NCT00121303 | Completed Phase 3

• 4 other identifiers: CDR0000433422SAKK-AML-43EU-20514HOVON-AML-43
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 6

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cytarabine and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as gemtuzumab ozogamicin, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether cytarabine and daunorubicin followed by gemtuzumab ozogamicin is more effective than cytarabine and daunorubicin in treating acute myeloid leukemia or myelodysplastic syndromes. PURPOSE: This randomized phase III trial is studying cytarabine and two different doses of daunorubicin to see how well they work compared to cytarabine and daunorubicin followed by gemtuzumab ozogamicin in treating older patients with acute myeloid leukemia or myelodysplastic syndromes.

Conditions

Leukemia; Myelodysplastic Syndromes

Keywords

adult acute monocytic leukemia (M5b); adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); adult acute megakaryoblastic leukemia (M7); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myelomonocytic leukemia (M4); adult acute monoblastic leukemia (M5a); refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; secondary acute myeloid leukemia; untreated adult acute myeloid leukemia; de novo myelodysplastic syndromes; adult acute minimally differentiated myeloid leukemia (M0); 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); secondary myelodysplastic syndromes

Outcome Measures

Primary Outcomes (2)

• Event-free survival after induction therapy

• Disease-free survival after maintenance therapy

Secondary Outcomes (6)

• Complete remission (CR) rate after induction therapy

• Overall survival after induction therapy

• Toxicity after induction therapy

• Toxicity after maintenance therapy

• Probability of relapse and death in first CR after maintenance therapy

Study Arms (4)

Arm A low dose Dauno

ACTIVE COMPARATOR

Induction 45 mg Dauno

Drug: cytarabine; Drug: daunorubicin hydrochloride

ARM B high dose Dauno

EXPERIMENTAL

Induction 90 mg Dauno

Drug: cytarabine; Drug: daunorubicin hydrochloride

Arm 1 no further treatment

NO INTERVENTION

Arm 2 Mylotarg

EXPERIMENTAL

Post induction treatment with Mylotarg

Drug: gemtuzumab ozogamicin

Interventions

cytarabine DRUG

ARM B high dose Dauno; Arm A low dose Dauno

daunorubicin hydrochloride DRUG

ARM B high dose Dauno; Arm A low dose Dauno

gemtuzumab ozogamicin DRUG

Arm 2 Mylotarg

Eligibility Criteria

• Age: 61 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed diagnosis of 1 of the following: * Acute myeloid leukemia (AML) * M0-M2 or M4-M7 FAB subtype * No AML with cytogenetic abnormality t(15;17) (M3) * Patients with secondary AML progressing from prior myelodysplasia\* or biphenotypic leukemia are eligible * Refractory anemia with excess blasts (RAEB) or RAEB in transformation * International Prognostic Scoring System score ≥ 1.5 NOTE: \*Any prior hematological disease of ≥ 4 months duration * No chronic myelogenous leukemia in blastic crisis * No prior polycythemia rubra vera * No primary myelofibrosis PATIENT CHARACTERISTICS: Age * 61 and over Performance status * WHO 0-2 Life expectancy * Not specified Hematopoietic * Not specified Hepatic * ALT and/or AST ≤ 2.5 times upper limit of normal (ULN)\* * Bilirubin ≤ 2 times ULN\* NOTE: \*Unless elevation is caused by organ infiltration by AML Renal * Creatinine ≤ 2 times ULN\* NOTE: \*Unless elevation is caused by organ infiltration by AML Cardiovascular * No myocardial infarction within the past 6 months * LVEF \> 50% by MUGA, echocardiogram, or other methods * No unstable angina * No unstable cardiac arrhythmia * No severe and/or uncontrolled hypertension Other * No uncontrolled diabetes * No severe and/or uncontrolled infection * No other severe and/or uncontrolled medical condition PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * More than 6 months since prior chemotherapy Endocrine therapy * Not specified Radiotherapy * Not specified Surgery * Not specified Other * No prior induction therapy for AML or myelodysplastic syndromes

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Stichting Hemato-Oncologie voor Volwassenen Nederland: lead

Study Sites (6)

North Hampshire Hospital

Basingstoke, England, RG24 9NA, United Kingdom

Location

Kent and Canterbury Hospital

Canterbury, England, CT2 7NR, United Kingdom

Location

Medway Maritime Hospital

Gillingham Kent, England, ME7 5NY, United Kingdom

Location

Maidstone Hospital

Maidstone, England, ME16 9QQ, United Kingdom

Location

Royal Cornwall Hospital

Truro, Cornwall, England, TR1 3LJ, United Kingdom

Location

University Hospital of Wales

Cardiff, Wales, CF14 4XW, United Kingdom

Location

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Leukemia, Monocytic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Anemia, Refractory, with Excess of Blasts; Congenital Abnormalities

Interventions

Cytarabine; Daunorubicin; Gemtuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Anemia, Refractory; Anemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Calicheamicins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jonathan Kell, MRCPath

  University Hospital of Wales

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2005
• First Posted: July 21, 2005
• Study Start: January 1, 2005
• Primary Completion: January 1, 2009
• Study Completion: June 1, 2016
• Last Updated: September 20, 2016

Record last verified: 2016-09

Locations

GB (6)