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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Stichting Hemato-Oncologie voor Volwassenen Nederland
ClinicalTrials.gov Identifier:
NCT00121303
First received: July 19, 2005
Last updated: June 26, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: gemtuzumab ozogamicin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomised Induction and Post Induction Therapy in Older Patients (≥61 Years of Age) With Acute Myeloid Leukemia (AML) and Refractory Anemia With Excess Blasts (RAEB, RAEB-t)

Resource links provided by NLM:


Further study details as provided by Stichting Hemato-Oncologie voor Volwassenen Nederland:

Primary Outcome Measures:
  • Event-free survival after induction therapy [ Designated as safety issue: No ]
  • Disease-free survival after maintenance therapy [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete remission (CR) rate after induction therapy [ Designated as safety issue: No ]
  • Overall survival after induction therapy [ Designated as safety issue: No ]
  • Toxicity after induction therapy [ Designated as safety issue: Yes ]
  • Toxicity after maintenance therapy [ Designated as safety issue: Yes ]
  • Probability of relapse and death in first CR after maintenance therapy [ Designated as safety issue: No ]
  • Overall survival after maintenance therapy [ Designated as safety issue: No ]

Estimated Enrollment: 600
Study Start Date: January 2005
Arms Assigned Interventions
Active Comparator: Arm A low dose Dauno
Induction 45 mg Dauno
Drug: cytarabine Drug: daunorubicin hydrochloride
Experimental: ARM B high dose Dauno
Induction 90 mg Dauno
Drug: cytarabine Drug: daunorubicin hydrochloride
No Intervention: Arm 1 no further treatment
Experimental: Arm 2 Mylotarg
Post induction treatment with Mylotarg
Drug: gemtuzumab ozogamicin

  Hide Detailed Description

Detailed Description:

OBJECTIVES:

Primary

  • Compare the event-free and disease-free survival of older patients with acute myeloid leukemia, refractory anemia with excess blasts (RAEB), or RAEB in transformation treated with induction therapy comprising cytarabine in combination with two different doses of daunorubicin followed by cytarabine alone with or without post-induction therapy comprising gemtuzumab ozogamicin.

Secondary

  • Compare the complete remission rate in patients treated with these regimens.
  • Compare the overall survival of patients treated with these regimens.
  • Compare the toxicity of these regimens in these patients.
  • Determine the probability of relapse and death during first complete remission in patients treated with post-induction gemtuzumab ozogamicin.
  • Correlate prognostic factors (e.g., CD33 positivity, multidrug resistance phenotype, or cytogenetics) with probability of complete remission and overall, event-free, and disease-free survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and diagnosis (acute myeloid leukemia [AML] vs myelodysplastic syndromes [MDS]) for induction therapy. Patients are stratified according to participating center, diagnosis (AML vs MDS), induction treatment arm (I vs II), and response to induction therapy (complete remission [CR] vs no CR) for post-induction therapy.

  • Induction therapy (course 1): Patients are randomized to 1 of 2 induction treatment arms.

    • Arm I: Patients receive cytarabine IV continuously on days 1-7 and daunorubicin IV over 3 hours on days 1-3.
    • Arm II: Patients receive cytarabine as in arm I and daunorubicin as in arm I but at a higher dose.

Approximately 28-35 days after the start of course 1 (or sooner if the bone marrow shows evidence of resistant disease), patients in both arms proceed to course 2 of induction therapy.

  • Induction therapy (course 2): All patients receive cytarabine IV over 6 hours twice daily on days 1-6.

After completion of course 2, patients undergo assessment of remission status. Patients who do not achieve CR are removed from the study. Patients achieving CR proceed to post-induction therapy and undergo a second randomization.

  • Post-induction therapy: Patients are randomized to 1 of 2 post-induction treatment arms.

    • Arm I: Patients receive no further chemotherapy.
    • Arm II: Patients receive gemtuzumab ozogamicin IV over 2 hours on days 1, 29, and 57 in the absence of disease relapse or unacceptable toxicity.

After completion of study treatment, patients are followed monthly for 1 year, every 3 months for 2 years, every 4-6 months for 2 years, and then periodically thereafter.

PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study within 4-5 years.

  Eligibility

Ages Eligible for Study:   61 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00121303

Locations
United Kingdom
North Hampshire Hospital
Basingstoke, England, United Kingdom, RG24 9NA
Kent and Canterbury Hospital
Canterbury, England, United Kingdom, CT2 7NR
Medway Maritime Hospital
Gillingham Kent, England, United Kingdom, ME7 5NY
Maidstone Hospital
Maidstone, England, United Kingdom, ME16 9QQ
Royal Cornwall Hospital
Truro, Cornwall, England, United Kingdom, TR1 3LJ
University Hospital of Wales
Cardiff, Wales, United Kingdom, CF14 4XW
Sponsors and Collaborators
Stichting Hemato-Oncologie voor Volwassenen Nederland
Investigators
Study Chair: Jonathan Kell, MRCPath University Hospital of Wales
  More Information

Additional Information:
No publications provided

Responsible Party: Stichting Hemato-Oncologie voor Volwassenen Nederland
ClinicalTrials.gov Identifier: NCT00121303     History of Changes
Other Study ID Numbers: CDR0000433422, SAKK-AML-43, EU-20514, HOVON-AML-43
Study First Received: July 19, 2005
Last Updated: June 26, 2013
Health Authority: Netherlands: Independent Ethics Committee

Keywords provided by Stichting Hemato-Oncologie voor Volwassenen Nederland:
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

Additional relevant MeSH terms:
Anemia, Refractory
Anemia, Refractory, with Excess of Blasts
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Anemia
Hematologic Diseases
Bone Marrow Diseases
Neoplasms by Histologic Type
Neoplasms
Precancerous Conditions
Cytarabine
Gemtuzumab
Daunorubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on July 26, 2014