Allogeneic Stem Cell Transplantation Followed By Targeted Immune Therapy In Average Risk Leukemia (AML/MDS/JMML)
Allogeneic stem cell transplantation (AlloSCT) followed by targeted immune therapy Gemtuzumab Ozogamicin patients with acute myeloid leukemia (AML)/juvenile myelomonocytic leukemia (JMML)/myelodysplastic syndromes (MDS) will be safe and well tolerated.
Acute Myelogenous Leukemia
Juvenile Myelomonocytic Leukemia
Drug: Graft-versus-host disease (GVHD) Prophylaxis
Drug: Gemtuzumab Ozogamicin
Drug: Anti-Thymocyte Globulin
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Allogeneic Stem Cell Transplantation Followed By Targeted Immune Therapy In Average Risk Acute Myelogenous Leukemia/Myelodysplastic Syndrome/Juvenile Myelomonocytic Leukemia (AML/MDS/JMML)|
- Maximal tolerated and/or biologically active dose of Gemtuzumab Ozogamicin (GO) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]To determine the maximal tolerated and/or biologically active dose of Gemtuzumab Ozogamicin (GO) (anti CD33 immunotoxin) therapy following reduced intensity (RI) allogeneic stem cell transplantation (alloSCT) in patients with average risk AML/JMML/MDS.
- Change of minimal residual disease [ Time Frame: Day 60, Day 100, Day 180, 1 year, 2 years ] [ Designated as safety issue: Yes ]To measure the changes, if applicable, of minimal residual disease prior to and after consolidation therapy with targeted immunotherapy in average risk AML/JMML/MDS post RI AlloSCT.
- Minor histocompatibility antigen (MHA) expression on acute myeloid leukemia (AML) tissue [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]To measure the minor histocompatibility antigen expression on AML tissue, donor and recipient, and the development of MHA specific cytotoxic T-lymphocytes (CTLs).
- Degree of mixed/complete donor chimerism [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]To determine the degree of mixed/complete donor chimerism after RI AlloSCT in patients with average risk AML/JMML/MDS.
- Event free survival (EFS) rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]To determine event free survival (EFS) after RI AlloSCT and targeted immunotherapy in patients with average risk AML/JMML/MDS.
- Overall survival (OS) rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]To determine overall survival (OS) after RI AlloSCT and targeted immunotherapy in patients with average risk AML/JMML/MDS.
|Study Start Date:||January 2003|
|Estimated Study Completion Date:||June 2014|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: Matched Family Donor
Stem Cell Transplant will be performed using the matched family donor SCT.
Other Name: Fludara®Drug: Busulfan
Other Name: Busulfex®Drug: Graft-versus-host disease (GVHD) Prophylaxis
Can be FK506 (Tacrolimus/Prograf®), mycophenolate mofetil ((MMF)/Cellcept®), or methotrexate (MTX, amethopterin)Drug: Gemtuzumab Ozogamicin
Other Name: Mylotarg®
Experimental: Unrelated Donor
Stem Cell Transplant will be performed using Unrelated Donor SCT.
Drug: Anti-Thymocyte Globulin
Unrelated Donors only
Other Name: Thymoglobulin®Drug: Isotretinoin
JMML patients only
Gemtuzumab Ozogamicin (CMA-676) is a chemotherapeutic agent consisting of a recombinant humanized anti-CD33 antibody conjugated with calicheamicin, a highly potent cytotoxic antitumor antibiotic. The antibody portion of Gemtuzumab binds specifically to the CD33 antigen, a sialic acid-dependent adhesion protein expressed on the surface of leukemic blasts, normal and leukemic myeloid colony-forming cells, including leukemic clonogenic precursors, but excluding pluripotent hematopoietic stem cells and nonhematopoietic cells. This results in formation of a complex that is internalized, upon which the calicheamicin derivative is released within the lysosomes of the myeloid cell. The free calicheamicin derivative then binds to deoxyribonucleic acid (DNA), resulting in DNA double strand breaks and consequential cell death. Over 80% of AML patients possess myeloid blast cells with CD33 surface antigen expression.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01020539
|United States, New York|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|Principal Investigator:||Monica Bhatia, MD||Columbia University|