Text Size

Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Patients With AML Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00049517
First received: November 12, 2002
Last updated: January 10, 2013
Last verified: January 2013
History of Changes
  Purpose

RATIONALE: Giving combination chemotherapy before a stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the transplanted stem cells. When the healthy stem cells are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. If the patient's stem cells are to be transplanted, the patient is also treated with a monoclonal antibody, such as gemtuzumab ozogamicin, to kill any remaining cancer cells or deliver cancer-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without gemtuzumab ozogamicin followed by stem cell transplant in treating acute myeloid leukemia.

PURPOSE: This randomized phase III trial is studying combination chemotherapy, gemtuzumab ozogamicin, and stem cell transplant to see how well they work compared to combination chemotherapy and peripheral stem cell transplant alone in treating patients with acute myeloid leukemia.


Condition Intervention Phase
Leukemia
 Biological: sargramostim
Drug: busulfan
Drug: cyclophosphamide
Drug: cytarabine
Drug: gemtuzumab ozogamicin (GO)
Drug: Daunorubicin
Procedure: Autologous HCT
Procedure: Allogeneic HCT
 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: A Phase III Trial in Adult Acute Myeloid Leukemia: Daunorubicin Dose-Intensification Prior to Risk-Allocated Autologous Stem Cell Transplantation

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Overall Survival (Induction Phase) [ Time Frame: Assessed during the first 4 months, then at least every three months for 2 years. then every six months until 5 years after study entry and every 12 months thereafter. ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from randomization in the induction phase to death.

  • Disease-free Survival (Consolidation Phase) [ Time Frame: Assessed during the first 4 months, then at least every three months for 2 years. then every six months until five years after study entry, and every 12 months thereafter. ] [ Designated as safety issue: No ]
    Disease-free survival is defined from the time of the confirmation of a complete remission via biopsy to the relapse of the disease.


Secondary Outcome Measures:
  • Overall Survival (Consolidation Phase) [ Time Frame: Assessed during the first 4 months, then at least every three months for 2 years. then every six months until five years after study entry, and every 12 months thereafter. ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from randomization in the consolidation phase to death.


Enrollment: 657
Study Start Date: December 2002
Estimated Study Completion Date: October 2016
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Standard Daunorubicin Then Autologous HCT

Induction: Patients receive standard-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course.

Consolidation/Transplant:

Before initiating consolidation therapy, patients with CR were randomized to a standard or an investigational arm. All patients received 2 cycles of high-dose cytarabine therapy (3 g/m2 given IV over a 3-hour period every 12 hours every other day for a total of 6 doses), followed by sargramostim 250 μg/m2 until recovery of blood counts.

The patients undergoing autologous hematopoietic cell transplantation (HCT) received intravenous busulfan 0.8 mg/kg every 6 hours for 16 doses (without pharmacokinetic sampling) followed by intravenous cyclophosphamide 60 mg/kg daily for 2 days.

 Biological: sargramostim
Given IV or as an injection
Other Name: Leukine
Drug: busulfan
Given IV
Other Name: Myleran
Drug: cyclophosphamide
Given IV
Other Names:
  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune
  • cytophosphane
Drug: cytarabine
Given as a continuous infusion
Other Name: cytosine arabinoside
Drug: Daunorubicin
Given intravenously daily for 3 days at a dose of either 45 or 90 mg/m2.
Other Names:
  • daunomycin
  • daunomycin cerubidine
Procedure: Autologous HCT
Autologous hematopoietic cell transplantation
Other Name: Autologous hematopoietic cell transplantation
Experimental: High-dose Daunorubicin Then Autologous HCT

Induction: Patients receive high-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course.

Consolidation/Transplant:

Before initiating consolidation therapy, patients with CR were randomized to a standard or an investigational arm. All patients received 2 cycles of high-dose cytarabine therapy (3 g/m2 given IV over a 3-hour period every 12 hours every other day for a total of 6 doses), followed by sargramostim 250 μg/m2 until recovery of blood counts.

The patients undergoing autologous hematopoietic cell transplantation (HCT) received intravenous busulfan 0.8 mg/kg every 6 hours for 16 doses (without pharmacokinetic sampling) followed by intravenous cyclophosphamide 60 mg/kg daily for 2 days.

 Biological: sargramostim
Given IV or as an injection
Other Name: Leukine
Drug: busulfan
Given IV
Other Name: Myleran
Drug: cyclophosphamide
Given IV
Other Names:
  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune
  • cytophosphane
Drug: cytarabine
Given as a continuous infusion
Other Name: cytosine arabinoside
Drug: Daunorubicin
Given intravenously daily for 3 days at a dose of either 45 or 90 mg/m2.
Other Names:
  • daunomycin
  • daunomycin cerubidine
Procedure: Autologous HCT
Autologous hematopoietic cell transplantation
Other Name: Autologous hematopoietic cell transplantation
Experimental: Standard Daunorubicin Then GO/Autologous HCT

Induction: Patients receive standard-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course.

Consolidation/Transplant:

Before initiating consolidation therapy, patients with CR were randomized to a standard or an investigational arm. All patients received 2 cycles of high-dose cytarabine therapy (3 g/m2 given IV over a 3-hour period every 12 hours every other day for a total of 6 doses), followed by sargramostim 250 μg/m2 until recovery of blood counts. patients randomized to the investigational arm received a single dose of Gemtuzumab ozogamicin (GO) at 6 mg/m2 followed by sargramostim 250 μ/m2 until recovery of counts.

The patients undergoing autologous HCT received intravenous busulfan 0.8 mg/kg every 6 hours for 16 doses followed by intravenous cyclophosphamide 60 mg/kg daily for 2 days.

 Biological: sargramostim
Given IV or as an injection
Other Name: Leukine
Drug: busulfan
Given IV
Other Name: Myleran
Drug: cyclophosphamide
Given IV
Other Names:
  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune
  • cytophosphane
Drug: cytarabine
Given as a continuous infusion
Other Name: cytosine arabinoside
Drug: gemtuzumab ozogamicin (GO)
Given IV
Other Name: Mylotarg
Drug: Daunorubicin
Given intravenously daily for 3 days at a dose of either 45 or 90 mg/m2.
Other Names:
  • daunomycin
  • daunomycin cerubidine
Procedure: Autologous HCT
Autologous hematopoietic cell transplantation
Other Name: Autologous hematopoietic cell transplantation
Experimental: High-dose Daunorubicin Then GO/Autologous HCT

Induction: Patients receive high-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course.

Consolidation/Transplant:

Before initiating consolidation therapy, patients with CR were randomized to a standard or an investigational arm. All patients received 2 cycles of high-dose cytarabine therapy (3 g/m2 given IV over a 3-hour period every 12 hours every other day for a total of 6 doses), followed by sargramostim 250 μg/m2 until recovery of blood counts. patients randomized to the investigational arm received a single dose of Gemtuzumab ozogamicin (GO) at 6 mg/m2 followed by sargramostim 250 μ/m2 until recovery of counts.

The patients undergoing autologous HCT received intravenous busulfan 0.8 mg/kg every 6 hours for 16 doses followed by intravenous cyclophosphamide 60 mg/kg daily for 2 days.

 Biological: sargramostim
Given IV or as an injection
Other Name: Leukine
Drug: busulfan
Given IV
Other Name: Myleran
Drug: cyclophosphamide
Given IV
Other Names:
  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune
  • cytophosphane
Drug: cytarabine
Given as a continuous infusion
Other Name: cytosine arabinoside
Drug: gemtuzumab ozogamicin (GO)
Given IV
Other Name: Mylotarg
Drug: Daunorubicin
Given intravenously daily for 3 days at a dose of either 45 or 90 mg/m2.
Other Names:
  • daunomycin
  • daunomycin cerubidine
Procedure: Autologous HCT
Autologous hematopoietic cell transplantation
Other Name: Autologous hematopoietic cell transplantation
Active Comparator: Standard Daunorubicin Then Allogeneic HCT or no Consolidation

Induction: Patients receive standard-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course.

Consolidation/Transplant:

Patients without CR did not receive any consolidation treatment. Patients in CR with an unfavorable cytogenetic profile or an initial white blood cell count > 100,000/μL were to proceed to allogeneic HCT if they had a suitable human leukocyte antigen (HLA)-matched sibling donor available.

 Drug: cytarabine
Given as a continuous infusion
Other Name: cytosine arabinoside
Drug: Daunorubicin
Given intravenously daily for 3 days at a dose of either 45 or 90 mg/m2.
Other Names:
  • daunomycin
  • daunomycin cerubidine
Procedure: Allogeneic HCT
Allogeneic hematopoietic cell transplantation
Other Name: Allogeneic hematopoietic cell transplantation
Experimental: High-dose Daunorubicin Then Allogeneic HCT or no Consolidation

Induction: Patients receive high-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course.

Consolidation/Transplant:

Patients without CR did not receive any consolidation treatment. Patients in CR with an unfavorable cytogenetic profile or an initial white blood cell count > 100,000/μL were to proceed to allogeneic HCT if they had a suitable human leukocyte antigen (HLA)-matched sibling donor available.

 Drug: cytarabine
Given as a continuous infusion
Other Name: cytosine arabinoside
Drug: Daunorubicin
Given intravenously daily for 3 days at a dose of either 45 or 90 mg/m2.
Other Names:
  • daunomycin
  • daunomycin cerubidine
Procedure: Allogeneic HCT
Allogeneic hematopoietic cell transplantation
Other Name: Allogeneic hematopoietic cell transplantation

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   16 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Morphologically confirmed acute myeloid leukemia (AML) (greater than 20% blasts in the peripheral blood or marrow) meeting any of the following criteria:

    • Recurrent cytogenetic translocations

      • t(8;21)(q22;q22)

      • Bone marrow eosinophil abnormalities

        • inv(16)(p13;q22)
        • t(16;16)(p13;q22)
      • 11q23 abnormalities
    • Multilineage dysplasia without presence of myelodysplastic syndromes (MDS)
    • Minimally differentiated AML
    • AML without maturation
    • AML with maturation
    • AML not otherwise categorized
    • Acute myelomonocytic leukemia
    • Acute monocytic leukemia
    • Acute erythroid leukemia
    • Acute megakaryocytic leukemia
    • Acute basophilic leukemia
  • Patients undergoing allogeneic transplantation must have a sibling donor match defined as human leukocyte antigen (HLA) match or haplotype match with one locus mismatch on other haplotype
  • Age 16 to 60
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-4
  • Aspartate aminotransferase (AST) less than 4 times upper limit of normal (ULN)
  • Alkaline phosphatase less than 4 times ULN
  • Creatinine no greater than 2.0 mg/dL
  • Creatinine clearance at least 50 mL/min
  • Left ventricular ejection fraction (LVEF) at least 45% by post-induction multigated acquisition (MUGA) scan
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative
  • Prior hydroxyurea allowed
  • Prior corticosteroids allowed

Exclusion Criteria:

  • Recurrent cytogenetic translocations

    • Acute promyelocytic leukemia (PML) with t(15;17)(q22;q21)
    • Variant acute PML with t(v;17)
  • Multilineage dysplasia with prior MDS

  • Acute panmyelosis with myelofibrosis

    • Blastic transformation of chronic myelogenous leukemia
    • Secondary AML (chemotherapy-induced or evolved from MDS)
    • Pregnant or nursing
    • Bilirubin greater than 2.0 mg/dL (unless related to Gilbert's syndrome or hemolysis)
    • Significant cardiac disease requiring active therapy (e.g., digoxin, diuretics, antiarrhythmics, or antianginal medications)
    • Prior biologic therapy
    • Prior cytotoxic chemotherapy for any malignancy
    • Prior radiotherapy for any malignancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00049517

  Show 99 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Hugo F. Fernandez, MD H. Lee Moffitt Cancer Center and Research Institute
  More Information

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

Publications:
Fernandez HF, Sun Z, Bennett JM, et al.: A single dose of gemtuzumab-ozogamicin (GO) in consolidation prior to autologous transplant for younger patients with newly diagnosed acute myeloid (AML) is safe but has no effect on disease free survival: interim results of Eastern Cooperative Oncology Group study (E1900). [Abstract] Biol Blood Marrow Transplant 14 (2): A-52, 21-2, 2008.
Fernandez HF, Kim HT, Bennett JM, et al.: Gemtuzumab-ozogamicin (GO; mylotarg®) as part of consolidation therapy for AML before autograft: low incidence of hepatic veno-occlusive disease. [Abstract] Biol Blood Marrow Transplant 11 (2 Suppl 1): A-187, 2005.

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00049517     History of Changes
Other Study ID Numbers: CDR0000258113, U10CA021115, E1900
Study First Received: November 12, 2002
Results First Received: January 10, 2013
Last Updated: January 10, 2013
Health Authority: United States: Federal Government

Keywords provided by Eastern Cooperative Oncology Group:
acute myeloid leukemia
autologous transplantation
gemtuzumab ozogamicin

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Busulfan
Cyclophosphamide
Cytarabine
Gemtuzumab
Daunorubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
 Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antirheumatic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on June 13, 2013