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Gemtuzumab Ozogamicin in Treating Young Patients With Newly Diagnosed Acute Myeloid Leukemia Undergoing Remission Induction and Intensification Therapy

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ClinicalTrials.gov Identifier: NCT00070174
Recruitment Status : Completed
First Posted : October 7, 2003
Last Update Posted : February 20, 2014
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date  ICMJE October 3, 2003
First Posted Date  ICMJE October 7, 2003
Last Update Posted Date February 20, 2014
Study Start Date  ICMJE December 2003
Actual Primary Completion Date September 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 9, 2007)
  • Safety
  • Complete remission rate
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2007)
  • Feasibility
  • Effect of karyotypic abnormalities
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gemtuzumab Ozogamicin in Treating Young Patients With Newly Diagnosed Acute Myeloid Leukemia Undergoing Remission Induction and Intensification Therapy
Official Title  ICMJE Treatment of Newly Diagnosed Childhood Acute Myeloid Leukemia (AML) Using Intensive MRC-Based Therapy and Gemtuzumab Ozogamicin (GMTZ): A COG Pilot Study
Brief Summary

RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as gemtuzumab ozogamicin, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

PURPOSE: This phase II trial is studying how well gemtuzumab ozogamicin works in treating young patients who are undergoing remission induction, intensification therapy, and allogeneic bone marrow transplant for newly diagnosed acute myeloid leukemia.

Detailed Description

OBJECTIVES:

Primary

  • Determine the safety of gemtuzumab ozogamicin in children with newly diagnosed acute myeloid leukemia undergoing intensive remission induction and intensification therapy.
  • Determine the complete remission rate of patients treated with this regimen.

Secondary

  • Determine the feasibility of performing biological studies (e.g., FLT3-ITD and MRD) for risk group stratification in these patients.
  • Determine the effect of karyotypic abnormalities on survival in patients treated with this regimen.

OUTLINE: This is a multicenter study.

  • Induction I: Patients receive high-dose cytarabine (ARA-C) IV twice daily on days 1-10; daunorubicin IV over 6 hours on days 1, 3, and 5; etoposide IV over 4 hours on days 1-5; and gemtuzumab ozogamicin IV over 2 hours on day 6. Patients with CNS-negative disease receive ARA-C intrathecally (IT) on day 1. Patients with CNS-positive disease receive ARA-C IT twice weekly for 2-3 weeks. Between days 28-35, patients are evaluated. Patients achieving remission or who have no more than 20% blasts proceed to induction II.
  • Induction II: Patients receive ARA-C IV twice daily on days 1-8; ARA-C IT on day 1; and daunorubicin IV and etoposide IV as in induction I. Between days 28-35 patients are evaluated. Patients achieving complete remission proceed to intensification course I.
  • Intensification course I: Patients receive ARA-C IV over 1 hour twice daily on days 1-5; ARA-C IT as in induction II; and etoposide IV over 1 hour on days 1-5. Patients are evaluated at day 28. Patients with a 5/6 or 6/6 matched family donor proceed to allogeneic bone marrow transplantation. All other patients in complete remission proceed to intensification course II.
  • Intensification course II: Patients receive ARA-C IV over 2 hours twice daily on days 1-4; ARA-C IT as in induction II; mitoxantrone IV over 1 hour on days 3-6; and gemtuzumab ozogamicin IV over 2 hours on day 7. Patients are evaluated on day 28 and then proceed to intensification course III.
  • Intensification course III: Patients receive ARA-C IV over 3 hours twice daily on days 1, 2, 8, and 9 and asparaginase intramuscularly on days 2 and 9.
  • Allogeneic bone marrow transplantation: Patients receive a preparative regimen comprising busulfan IV over 2 hours 4 times daily on days -9 to -6 and cyclophosphamide IV over 1 hour once daily on days -5 to -2. Allogeneic stem cells are infused on day 0.
  • Graft-versus-host disease prophylaxis: Patients receive oral or IV cyclosporine twice daily on days -1 to 50 and methotrexate IV once daily on days 1, 3, 6, and 11.

In all courses, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly for 6 months, every 2 months for 6 months, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 330 patients will be accrued for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leukemia
Intervention  ICMJE
  • Drug: asparaginase
  • Drug: busulfan
  • Drug: cyclophosphamide
  • Drug: cyclosporine
  • Drug: cytarabine
  • Drug: daunorubicin hydrochloride
  • Drug: etoposide
  • Drug: gemtuzumab ozogamicin
  • Drug: methotrexate
  • Drug: mitoxantrone hydrochloride
  • Procedure: allogeneic bone marrow transplantation
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 19, 2014)
350
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE December 2013
Actual Primary Completion Date September 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Newly diagnosed primary acute myeloid leukemia (AML)

    • At least 20% bone marrow blasts
    • Meets the customary FAB criteria for AML

      • Patients with cytopenias and bone marrow blasts who do not meet the FAB criteria are eligible provided they have a karyotypic abnormality characteristic of de novo AML (e.g., t[8;21], inv16, or t[16;16]) OR they have the unequivocal presence of megakaryoblasts
    • Isolated granulocytic sarcoma (myeloblastoma) allowed regardless of the results outlined above
  • Previously untreated disease
  • No promyelocytic leukemia (FAB M3)
  • No documented myelodysplastic syndromes (preleukemia) (e.g., chronic myelomonocytic leukemia, refractory anemia [RA], RA with excess blasts, or RA with ringed sideroblasts)
  • No juvenile myelomonocytic leukemia
  • No Fanconi's anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndrome
  • No Down syndrome

PATIENT CHARACTERISTICS:

Age

  • 1 month to 21 years* NOTE: *Children under 1 month of age who have progressive disease are allowed

Performance status

  • Karnofsky 50-100% (over 16 years of age) OR
  • Lansky 50-100% (ages 1 to 16)* NOTE: Children under 1 year of age do not require a performance status

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • No inadequate liver function

Renal

  • No inadequate renal function
  • No hyperuricemia (greater than 8.0 mg/dL)
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) at least 70 mL/min OR an equivalent normal GFR OR
  • Creatinine no greater than 1.5 times normal

Cardiovascular

  • Shortening fraction at least 27% by echocardiogram OR
  • Ejection fraction at least 50% by MUGA

Pulmonary

  • No proven or suspected pneumonia

Other

  • Not pregnant or nursing
  • No proven or suspected sepsis or meningitis

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy except intrathecal cytarabine administered that was administered at diagnosis

Endocrine therapy

  • Prior topical and inhalation steroids allowed
  • No concurrent steroids as antiemetics

Radiotherapy

  • No prior radiotherapy

Surgery

  • Not specified

Other

  • No prior antileukemic therapy
  • No concurrent pressor agent or ventilatory support unless approved by the study chair
  • No concurrent participation in another COG therapeutic study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Puerto Rico,   Switzerland,   United States
Removed Location Countries Netherlands,   New Zealand
 
Administrative Information
NCT Number  ICMJE NCT00070174
Other Study ID Numbers  ICMJE AAML03P1
CDR0000330133 ( Other Identifier: Clinical Trials.gov )
COG-AAML03P1 ( Other Identifier: Children's Oncology Group )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Oncology Group
Study Sponsor  ICMJE Children's Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Janet Franklin, MD, MPH Children's Hospital Los Angeles
PRS Account Children's Oncology Group
Verification Date February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP