SCT Plus Immune Therapy in Average Risk AML/MDS

Study Overview
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Brief Summary
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Allogeneic stem cell transplantation followed by targeted immune therapy with Gemtuzumab Ozogamicin (Mylotarg) will be given to patients with average risk AML or MDS.

Detailed Description
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Reduced intensity conditioning regimen of Busulfan (Bu) and Fludarabine (Flu) + Anti-Thymocyte Globulin (ATG ) (unrelated donors only) or reduced toxicity conditioning regimen of Bu/Flu/alemtuzumab, or reduced hepatic toxicity regimen of melphan/Flu/alemtuzumab and AlloSCT, followed by Gemtuzumab Ozogamicin consolidation in patients with average risk AML/MDS meeting eligibility criteria.

Official Title
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Allogeneic Stem Cell Transplantation Following by Targeted Immune Therapy) (Gemtuzumab Ozogamicin) in Average Risk Acute Myelogenous Leukemia and Myelodysplastic Syndrome (AML/MDS)

Conditions
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Acute Myelogenous Leukemia, Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: Gemtuzumab Ozogamicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Disease Status: AML 1st CR with a matched family donor AML 1st CR with unrelated donor AML 2nd CR or CRP MDS and < or = 5% bone marrow myeloblasts at diagnosis Disease Immunophenotype: Disease must express a minimum of > or = 10% CD33 positivity for patients with AML Organ Function: Adequate renal function, adequate liver function, adequate cardiac function, adequate pulmonary function Exclusion Criteria: Patients with active CNS AML disease at time of preparative regimen Secondary MDS Poor cytogenetics Female patients who are pregnant Karnofsky <70% or Lansky <50% if 10 years or less Age >25 years Seropositive for HIV

Ages Eligible for Study
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Maximum Age: 25 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: Gemtuzumab Ozogamicin<br>Consolidation therapy with GO will be administered between days 60 and 180 post transplantation when the ANC is >1000/mm3 and platelet count is >40,000/mm3 untransfused x 3 days after AlloSCT and again at minimum 8 weeks later. | Drug: Gemtuzumab Ozogamicin<br>* Gemtuzumab, 9.0 mg/m2, will be given IV over 2 hours two times post allogeneic transplantation.<br>* Other names: Mylotarg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to evaluate incidence of graft failure | If three or more of the first ten patients experience primary or secondary graft failure, we will discontinue the study. | Day +42 | 
| to evaluate survival rates | Event-free survival and overall survival after RI AlloSCT and targeted immunotherapy in patients with average risk AML/MDS. | 1 year | 
| to determine toxicity | to monitor for serious adverse events related to protocol investigational therapy | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minor histocompatibility antigen | To measure the minor histocompatibility antigen expression on AML tissue, donor and recipient, and the development of MHA specific CTLs post AlloSCT. | 1 year | 
| Chimerism | To determine the degree of mixed/complete donor chimerism after RI AlloSCT in patients with average risk AML/MDS. | 1 year | 
| Graft-versus-host disease | To estimate the risk of acute and chronic GVHD following RI AlloSCT and FK506/MMF GVHD prophylaxis in patients with average risk AML/MDS. | 1 Year |