Clinical Trial: Allogenic Stem Cell Transplantation in Patients With High Risk CD33+ AML/MDS/JMML

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Gemtuzumab Ozogamicin in Combination With Busulfan and Cyclophosphamid and Allogenic Stem Cell Transplantation in Patients With High Risk CD33+ Acute Myelogenous Leukemia/Myelodysplastic Syndrome/

Brief Summary:

The addition of gemtuzumab ozogamicin (GO) in combination with Busulfan/Cyclophosphamide followed by AlloSCT in patients with high risk CD33+ AML/JMML/MDS will be safe and well tolerated.

This study will attempt to determine the maximum tolerated dose of the immune therapy (gemtuzumab) when given in combination with the myeloablative (high dose) drugs used in this study for allogeneic stem cell transplant. (Part A)


Detailed Summary: Gemtuzumab Ozogamicin (CMA-676) is a chemotherapeutic agent consisting of 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 leukemia 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 the complex that is internalized, upon which calicheamicin derivative is released with in the lysosomes of the myeloid cell. The free calicheamicin derivative then binds to the DNA, resulting in DNA double strand breaks and consequential cell death.
Sponsor: New York Medical College

Current Primary Outcome: Maximal tolerated dose or tolerable dose of Gemtuzumab Ozogamicin (anti-CD33 immunotoxin) therapy combined with Busulfan/ Cyclophosphamide in the conditioning regimen prior to AlloSCT in patients with high risk CD33+ AML/JMML/MDS [ Time Frame: 1 year ]

Original Primary Outcome:

  • To determine the maximal tolerated dose or tolerable dose of Gemtuzumab Ozogamicin (anti-CD33 immunotoxin) therapy combined with Busulfan/ Cyclophosphamide in the conditioning regimen prior to AlloSCT in patients with high risk CD33+ AML/JMML/MDS [ Time Frame: Until end of study ]
  • To determine the feasibility and toxicity of combined ablation chemotherapy (Busulfan/Cyclophosphamide) and targeted immunotherapy, Gemtuzumab Ozogamicin (anti-CD33 immunotoxin) followed by AlloSCT in patients with high risk CD33+ AML/JMML/MDS. [ Time Frame: Until End of study ]
  • To determine overall response rate (CR + PR) (if applicable) following GO, busulfan and cyclophosphamide and AlloSCT in patients with measurable disease (relapse/refractory) with high risk CD33+ AML/JMML/MDS. [ Time Frame: Until end of study ]


Current Secondary Outcome:

  • Changes, if applicable, of minimal residual disease (cytogenetics, FISH, RT-PCR) in patients with high risk CD33+ AML/JMML/MDS after AlloSCT. [ Time Frame: 1 year ]
  • Progression Free Survival (PFS), overall survival (OS), and disease free survival (DFS), (if applicable), following GO, Bu/CY and AlloSCT in patients with high risk CD33+ AML/JMML/MDS. [ Time Frame: 1 year ]
  • Quality of life before and after GO, Bu/CY conditioning and AlloSCT in patients with high risk CD33+ AML/JMML/MDS [ Time Frame: 1 year ]


Original Secondary Outcome:

  • To measure the changes, if applicable, of minimal residual disease (cytogenetics, FISH, RT-PCR) in patients with high risk CD33+ AML/JMML/MDS after AlloSCT. [ Time Frame: Until end of study ]
  • To determine Progression Free Survival (PFS), overall survival (OS), and disease free survival (DFS), (if applicable), following GO, Bu/CY and AlloSCT in patients with high risk CD33+ AML/JMML/MDS. [ Time Frame: Until end of study ]
  • To determine the quality of life before and after GO, Bu/CY conditioning and AlloSCT in patients with high risk CD33+ AML/JMML/MDS [ Time Frame: Until end of study ]


Information By: New York Medical College

Dates:
Date Received: April 29, 2008
Date Started: May 2004
Date Completion:
Last Updated: April 20, 2015
Last Verified: April 2015