Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

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.

Further Study Information

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.

Eligibility 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

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

Trial Contact Information

Trial Lead Organizations/Sponsors

Children's Oncology Group

Janet Franklin

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00070174
Information obtained from ClinicalTrials.gov on November 20, 2012

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