Combination 5-azacitidine and Gemtuzumab Ozogamicin Therapy for Treatment of Relapsed Acute Myeloid Leukemia (AML)

Study Overview
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Brief Summary
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This study will test an experimental combination of the drugs Mylotarg and 5-azacitidine in the hopes of finding a treatment that may be effective against Acute Myeloid Leukemia that has come back after treatment.

Detailed Description
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In the Phase I portion of the study patients with a diagnosis of AML who have relapsed disease will be treated with an assigned number of doses of 5 azacitidine followed by Mylotarg administered two times over two weeks In the Phase II portion of the study patients will be treated with the dose of 5azacitidine determined to be safe in the Phase I portion of the study followed by Mylotarg. A sample of blood or bone marrow will be obtained prior to initiation of treatment and another sample obtained after treatment with 5-azacitidine but before Mylotarg and the samples will be tested in the laboratory to determine response to treatment.

Official Title
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A Phase I/II Trial of the Combination 5-azacitidine and Gemtuzumab Ozogamicin Therapy for Treatment of Relapsed AML

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: 5-Azacitidine
* Drug: Gemtuzumab ozogamicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Relapsed AML Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and life expectancy > 3 months ≥ 18 years old Previously untreated for current AML relapse Adequate organ function Written informed consent Exclusion Criteria: Pregnant or breast-feeding women Growth factors that support platelet or white cell number or function must not have been administered within the past 7 days Currently receiving another investigational drug Currently receiving other anti-cancer agents Uncontrolled infection HIV positive Received previous therapy with either Mylotarg or 5-azacitidine

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1 Dose Level 1<br>5-Azacitidine, Gemtuzumab ozogamicin 75 mg/m^2 5-Aza 2 days then GO at 3 mg/m^2 | Drug: 5-Azacitidine<br>* Given in cohorts of 3 starting with 2 doses of 5-azacitidine. The doses of 5-azacitidine will be escalated to 4 and then 6 doses if the dose escalation rules permit.<br>* Other names: Vidaz;Drug: Gemtuzumab ozogamicin<br>* Mylotarg given 2 times over 2 weeks<br>* Other names: Mylotarg;|
| Experimental: Phase 1 Dose Level 2<br>5-Azacitidine, Gemtuzumab ozogamicin 75mg/m^2 5-Aza for 4 days then GO at 6 mg/m^2 | Drug: 5-Azacitidine<br>* Given in cohorts of 3 starting with 2 doses of 5-azacitidine. The doses of 5-azacitidine will be escalated to 4 and then 6 doses if the dose escalation rules permit.<br>* Other names: Vidaz;Drug: Gemtuzumab ozogamicin<br>* Mylotarg given 2 times over 2 weeks<br>* Other names: Mylotarg;|
| Experimental: Phase I Dose Level 3<br>5-Azacitidine, Gemtuzumab ozogamicin 75 mg/m^2 5-Aza for 6 days then GO at 6 mg/m^2 | Drug: 5-Azacitidine<br>* Given in cohorts of 3 starting with 2 doses of 5-azacitidine. The doses of 5-azacitidine will be escalated to 4 and then 6 doses if the dose escalation rules permit.<br>* Other names: Vidaz;Drug: Gemtuzumab ozogamicin<br>* Mylotarg given 2 times over 2 weeks<br>* Other names: Mylotarg;|
| Experimental: Phase 2 Dose Level 1<br>5-Azacitidine, Gemtuzumab ozogamicin 75 mg/m^2 5-Aza for 6 days then GO at 6 mg/m^2 | Drug: 5-Azacitidine<br>* Given in cohorts of 3 starting with 2 doses of 5-azacitidine. The doses of 5-azacitidine will be escalated to 4 and then 6 doses if the dose escalation rules permit.<br>* Other names: Vidaz;Drug: Gemtuzumab ozogamicin<br>* Mylotarg given 2 times over 2 weeks<br>* Other names: Mylotarg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicities | MTD was the maximum number of 5-azacitadine doses (75mg/m2) at which fewer than 1/3 of patients experienced a DLT during cycle 1 of therapy based on CTCAE Version 3.0. In the phase I portion, we assessed 3 dose levels of azacitidine starting on day 1, with 6, 4, and 4 patients in cohort 1, 2, and 3, respectively. We identified no dose-limiting toxicities and identified the phase 2 dose as 75 mg/m2 of 5-azacitadine for 6 days. | up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Response to the Combination Treatment of Mylotarg With 5-azacitidine |  | Hematologic and Cytogeneic Response to treatment will be assessed when evaluated at the time the ANC has reached 1000/mm3 for three consecutive days, assessed up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML