Clinical Trial: Allogeneic Stem Cell Transplantation Followed By Targeted Immune Therapy In Average Risk Leukemia

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Allogeneic Stem Cell Transplantation Followed By Targeted Immune Therapy In Average Risk Acute Myelogenous Leukemia/Myelodysplastic Syndrome/Juvenile Myelomonocytic Leukemia

Brief Summary: 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.

Detailed Summary: 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.
Sponsor: Columbia University

Current Primary Outcome: Maximal tolerated and/or biologically active dose of Gemtuzumab Ozogamicin (GO) [ Time Frame: Up to 2 years ]

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.


Original Primary Outcome: To determine the feasibility and toxicity of a Reduced Intensity (RI) regimen, AlloSCT followed by targeted immune therapy, Gemtuzumab Ozogamicin (GO) , in average risk AML/JMML/MDS. [ Time Frame: 8 years ]

Current Secondary Outcome:

  • Change of minimal residual disease [ Time Frame: Day 60, Day 100, Day 180, 1 year, 2 years ]
    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.
  • Incidence of minor histocompatibility antigen (MHA) expression on acute myeloid leukemia (AML) tissue [ Time Frame: Up to 2 years ]
    To measure the minor histocompatibility antigen expression on AML tissue, donor and recipient, and the incidence of development of MHA specific cytotoxic T-lymphocytes (CTLs).
  • Degree of mixed/complete donor chimerism [ Time Frame: Up to 2 years ]
    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 ]
    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 ]
    To determine overall survival (OS) after RI AlloSCT and targeted immunotherapy in patients with average risk AML/JMML/MDS.


Original Secondary Outcome:

  • 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 [ Time Frame: 8 years ]
  • To measure the minor histocompatibility antigen expression on AML tissue, donor and recipient, and the development of MHA specific CTLs post [ Time Frame: 8 years ]
  • To determine the degree of mixed/complete donor chimerism after RI AlloSCT in patients with average risk AML/JMML/MDS. [ Time Frame: 8 years ]
  • To determine event free survival (EFS) and overall survival (OS) after RI AlloSCT and targeted immunotherapy in patients with average risk AML/JMML/MDS [ Time Frame: 8 years ]
  • To estimate the risk of acute and chronic GVHD following RI AlloSCT and FK506/MMF GVHD prophylaxis in patients with average risk AML/JMML/MDS [ Time Frame: 8 years ]
  • To determine the maximal tolerated and/or biologically active dose of Gemtuzumab Ozogamicin (GO) (anti CD33 immunotoxin) therapy following RI AlloSCT in patients with average risk AML/JMML/MDS. [ Time Frame: 8 years ]


Information By: Columbia University

Dates:
Date Received: November 23, 2009
Date Started: January 2005
Date Completion: April 2017
Last Updated: January 5, 2016
Last Verified: January 2016