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

Sponsors and Collaborators:	Children's Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00070174

Purpose

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.

Condition	Intervention	Phase
Leukemia	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	Phase II

MedlinePlus related topics: Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Cyclophosphamide Cytarabine Cytarabine hydrochloride Etoposide L-Asparaginase Daunorubicin hydrochloride Daunorubicin Methotrexate Mitoxantrone hydrochloride Mitoxantrone Cyclosporin Cyclosporine Gemtuzumab ozogamicin Etoposide phosphate Busulfan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Treatment of Newly Diagnosed Childhood Acute Myeloid Leukemia (AML) Using Intensive MRC-Based Therapy and Gemtuzumab Ozogamicin (GMTZ): A COG Pilot Study

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety [ Designated as safety issue: Yes ]
Complete remission rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Feasibility [ Designated as safety issue: No ]
Effect of karyotypic abnormalities [ Designated as safety issue: No ]

Study Start Date:

December 2003

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.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00070174

Show 148 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Janet Franklin, MD, MPH

Children's Hospital Los Angeles

More Information

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

Publications of Results:

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.

Other Publications:

Sung L, Alonzo TA, Gerbing RB, Aplenc R, Lange BJ, Woods WG, Feusner J, Franklin J, Patterson MJ, Gamis AS. Respiratory syncytial virus infections in children with acute myeloid leukemia: A report from the Children's Oncology Group. Pediatr Blood Cancer. 2008 Aug 4; [Epub ahead of print]

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.

Study ID Numbers:	CDR0000330133, COG-AAML03P1
Study First Received:	October 3, 2003
Last Updated:	December 31, 2008
ClinicalTrials.gov Identifier:	NCT00070174
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

untreated childhood acute myeloid leukemia and other myeloid malignancies
childhood acute monocytic leukemia (M5b)
childhood acute megakaryocytic leukemia (M7)
childhood acute minimally differentiated myeloid leukemia (M0)
childhood acute myeloblastic leukemia with maturation (M2)

childhood acute myeloblastic leukemia without maturation (M1)
childhood acute myelomonocytic leukemia (M4)
childhood acute monoblastic leukemia (M5a)
childhood acute erythroleukemia (M6)

Study placed in the following topic categories:

Leukemia, Monocytic, Acute
Daunorubicin
Cyclosporine
Clotrimazole
Miconazole
Acute myelomonocytic leukemia
Cyclophosphamide
Di Guglielmo's syndrome
Leukemia, Myeloid, Acute
Etoposide phosphate
Cyclosporins
Antibodies, Monoclonal
Leukemia
Methotrexate
Acute erythroblastic leukemia

Acute myelocytic leukemia
Etoposide
Cytarabine
Immunoglobulins
Asparaginase
Tioconazole
Acute myelogenous leukemia
Myeloproliferative Disorders
Leukemia, Myeloid
Gemtuzumab
Folic Acid
Leukemia, Myelomonocytic, Acute
Antibodies
Leukemia, Erythroblastic, Acute
Busulfan

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Reproductive Control Agents
Antibiotics, Antineoplastic
Sensory System Agents
Therapeutic Uses
Antifungal Agents
Abortifacient Agents
Analgesics
Alkylating Agents

Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Neoplasms by Histologic Type
Enzyme Inhibitors
Abortifacient Agents, Nonsteroidal
Folic Acid Antagonists
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Neoplasms
Myeloablative Agonists
Peripheral Nervous System Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009