This application involves a Phase II trial and related laboratory evaluation combining a two step biological approach for the treatment of chronic myelogenous leukemia (CML) using: 1) Interferon-alpha (IFN-alpha) and 2) A high affinity, recombinant humanized anti-CD33 monoclonal antibody, HuM195, that has been shown in studies performed at Memorial Sloan-Kettering Cancer Center to eliminate minimal residual disease as evidenced by the conversion of polymerase chain reaction (PCR) in patients with acute promyelocytic leukemia (APL). CML, a disease characterized by the Philadelphia (Ph) chromosome, can be followed on the molecular level by PCR for the BCR-ABL translocation. In this trial, the applicant will use IFN-alpha to cytoreduce patients with CML. Once a hematological remission is attained, he will administer HuM195 to achieve a long lasting cytogenetic remission. The antitumor effect will also be evaluated by bone marrow morphology and cytogenetics. Toxicity and immunogenicity of HuM195 will be determined. The ability to achieve a molecular remission will be tested by serial PCR assays, and correlated to response duration. In addition, laboratory studies will be done to investigate the mechanism of action of HuM195 and IFN-(ADCC) with cells from CML patients. Lastly, the applicants will explore whether HuM195 affects the adhesive properties of IFN-alpha on CML cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA072939-01
Application #
2010994
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Project Start
1996-12-15
Project End
1998-11-30
Budget Start
1996-12-15
Budget End
1997-11-30
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065