We are carrying out trials in adults with drug resistant hairy cell leukemia and in children with acute lymphoblastic leukemia. In a phase 1 trial in adults in which Robert Kreitman is the principal investigator, we have found that an intravenous dose of 50 ug//Kg is safe and has produced more than a 50% complete remissions in Hiary Cell Leukemia. Based on this data the FDA has given permission for a pivotal trial to open and 3 patients have now been treated. In ALL the phase 1 trial is still ongoing and has been modified so children can receive 10 doses each cycle. In some patients complete remissions have been observed on this regimen. We have completed a phase 1 trial with SS1P in which Raffit Hassan is the principal investigator. In this trial SS1P was given with permetrexed/cis platinum, the standard mesothelin therapy;the response rate in this trial is higher that the published responses observed with chemotherapy alone. A randomized phase 2 trial to confirm this finding is being planned. Because SS1P is immunogenic and neutralizing antibodies usually form after 1 treatment cycle, we have carried out a trial in which SS1P is combined with 2 immunosuppressive drugs, pentostatin and cytoxan in patients who have failed standard therapy for mesothelioma. We have been able to give additional cycles to these patients and in addition have observed several major anti-tumor responses. This trial is now being expanded.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010020-18
Application #
8763050
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
18
Fiscal Year
2013
Total Cost
$989,879
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Hassan, Raffit; Alewine, Christine; Pastan, Ira (2016) New Life for Immunotoxin Cancer Therapy. Clin Cancer Res 22:1055-8
Pastan, Ira; Hassan, Raffit (2014) Discovery of mesothelin and exploiting it as a target for immunotherapy. Cancer Res 74:2907-12
Kelly, Ronan J; Sharon, Elad; Pastan, Ira et al. (2012) Mesothelin-targeted agents in clinical trials and in preclinical development. Mol Cancer Ther 11:517-25
Kreitman, Robert J; Tallman, Martin S; Robak, Tadeusz et al. (2012) Phase I trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox (CAT-8015 or HA22) in patients with hairy cell leukemia. J Clin Oncol 30:1822-8
Mehta, Ankit I; Choi, Bryan D; Ajay, Divya et al. (2012) Convection enhanced delivery of macromolecules for brain tumors. Curr Drug Discov Technol 9:305-10
Sharon, Elad; Zhang, Jingli; Hollevoet, Kevin et al. (2012) Serum mesothelin and megakaryocyte potentiating factor in pancreatic and biliary cancers. Clin Chem Lab Med 50:721-5
Mehta, Ankit I; Choi, Bryan D; Raghavan, Raghu et al. (2011) Imaging of convection enhanced delivery of toxins in humans. Toxins (Basel) 3:201-6
Kreitman, Robert J; Arons, Evgeny; Stetler-Stevenson, Maryalice et al. (2011) Recombinant immunotoxins and other therapies for relapsed/refractory hairy cell leukemia. Leuk Lymphoma 52 Suppl 2:82-6
Pastan, Ira; Onda, Masanori; Weldon, John et al. (2011) Immunotoxins with decreased immunogenicity and improved activity. Leuk Lymphoma 52 Suppl 2:87-90
Kreitman, Robert J; Pastan, Ira (2011) Antibody fusion proteins: anti-CD22 recombinant immunotoxin moxetumomab pasudotox. Clin Cancer Res 17:6398-405

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