Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	1 month to 21 years	NCI	COG-AAML03P1 NCT00070174, AAML03P1

Objectives

Primary

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

Secondary

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

Entry Criteria

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

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

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

Expected Enrollment

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

Outcomes

Safety
Complete remission rate

Feasibility
Effect of karyotypic abnormalities

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.

Franklin J, Alonzo T, Hurwitz CA, et al.: COG AAML03P1: efficacy and safety in a pilot study of intensive chemotherapy including gemtuzumab in children newly diagnosed with acute myeloid leukemia (AML). [Abstract] Blood 112 (11): A- 136, 2008.

Pollard JA, Alonzo T, Gerbing R, et al.: Correlation of CD 33 expression level with disease characteristics and response to gemtuzumab ozogamycin-containing chemotherapy in childhood AML. [Abstract] Blood 112 (11): A-148, 2008.

Ho PA, Alonzo TA, Gerbing RB, et al.: Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group. Blood 113 (26): 6558-66, 2009.[PUBMED Abstract]

Sung L, Alonzo TA, Gerbing RB, et al.: Respiratory syncytial virus infections in children with acute myeloid leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer 51 (6): 784-6, 2008.[PUBMED Abstract]

Pollard J, Alonzo T, Gerbing R, et al.: Prevalence and prognostic significance of c-KIT mutations in pediatric CBF AML patients enrolled on serial CCG/COG protocols. [Abstract] Blood 110 (11): A-1442, 2007.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Janet Franklin, MD, MPH, Protocol chair		Ph: 323-669-5600

Registry Information
Official Title		Treatment of Newly Diagnosed Childhood Acute Myeloid Leukemia (AML) Using Intensive MRC-Based Therapy and Gemtuzumab Ozogamicin (GMTZ): A COG Pilot Study
Trial Start Date		2003-12-29
Registered in ClinicalTrials.gov		NCT00070174
Date Submitted to PDQ		2003-08-15
Information Last Verified		2005-11-17
NCI Grant/Contract Number		CA98543

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