Gemtuzumab Ozogamicin in Treating Patients With Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This clinical trial studies the side effects of gemtuzumab ozogamicin and how well it works in treating patients with acute myeloid leukemia. Monoclonal antibodies, such as gemtuzumab ozogamicin, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them

Detailed Description
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PRIMARY OBJECTIVES: I. To study safety and efficacy single agent Gemtuzumab Ozogamicin (Mylotarg®) as induction therapy for patients with Acute Myeloid Leukemia (AML) who have relapsed after standard treatments or who are not candidates for standard consolidation treatment after Daunorubicin and cytosine arabinoside. SECONDARY OBJECTIVES: I. To correlate morbidity and mortality with the use of gemtuzumab (gemtuzumab ozogamicin) to specific subtypes of leukemia. II. To correlate gemtuzumab response to degree of cluster of differentiation (CD) 33 positivity. III. To correlate FMS-Related Tyrosine Kinase 3 (FLT 3)/nucleophosmin (NPM) status and CD 33 positivity to gemtuzumab response. IV. To document incidence of sinusoidal obstruction syndrome with the use of gemtuzumab. OUTLINE: Patients receive gemtuzumab ozogamicin intravenously (IV) over 2 hours on days 1 and 15. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up monthly for 1 year.

Official Title
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Safety and Efficacy of Gemtuzumab Ozogamicin (Mylotarg®) as for Treatment of Patients With CD33-Positive Acute Myeloid Leukemia (AML)

Conditions
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Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Promyelocytic Leukemia (M3), Recurrent Adult Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: gemtuzumab ozogamicin
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have confirmed relapsed or refractory acute myeloid leukemia and not a candidate for standard induction treatment after daunorubicin and cytosine arabinoside OR acute promyelocytic leukemia relapsed after all-trans retinoic acid (ATRA) or Arsenic trioxide therapy Patients must have an initial diagnosis of acute myeloid leukemia or biphenotypic acute leukemia Patients must have CD33 positivity of >= 30% Eastern Cooperative Oncology Group (ECOG) performance status =< 3 Karnofsky > 60% Total bilirubin within normal institutional limits Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2 X institutional upper limit of normal Creatinine within normal institutional limits OR creatinine clearance >= 30 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal The effects of Mylotarg on the developing human fetus are unknown; for this reason and because Mylotarg class agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients may not be receiving any other investigational agents for leukemia Patients with known untreated Hepatitis C because veno-occlusive disease and liver enzyme abnormalities have been associated with Mylotarg Uncontrolled intercurrent illness including, but not limited to active liver disease, ongoing or active sepsis requiring vasopressors or mechanical ventilation, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study because Mylotarg is a Class D agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Mylotarg, breastfeeding should be discontinued if the mother is treated with Mylotarg Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Mylotarg; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated Congestive Heart Failure (CHF) with an ejection fraction < 30% Glomerular filtration rate (GFR) < 30ml/min Active central nervous system (CNS) involvement of leukemia Philadelphia chromosome + acute lymphoblastic leukemia (ALL) Prior hematopoietic transplant in last 3 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (monoclonal antibody therapy)<br>Patients receive gemtuzumab ozogamicin IV over 2 hours on days 1 and 15. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. | Drug: gemtuzumab ozogamicin<br>* Given IV<br>* Other names: Mylotarg;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of serious adverse events | 95% confidence interval will be calculated. Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. | Approximately 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response, defined as complete remission (CR) and CR with incomplete platelet recovery (CRp) |  | At 28 days | 
| Safety analysis of gemtuzumab ozogamicin as induction therapy for patients with relapsed AML | Adverse event frequency and severity | Approximately 1 year | 
| Overall survival (OS) |  | Approximately 1 year | 
| Event-free survival (EFS) |  | Approximately 1 year | 
| Disease free survival (DFS) |  | Approximately 1 year |