Our goal is to evaluate the clinical activity of recombinant immunotoxins in patients. HA22 is licensed to MedImmune who is sponsoring trials in B cell malignancies. A multi center phase 1 trial of HA22 (CAT-8015, moxetumomab pasudotox) in drug resistant hairy cell leukemia is completed and a MTD established. There have been no dose limiting toxicities and over 50% of patients have achieved a complete remission. We are working with MedImmune and CTEP to get FDA permission to carry out a pivotal trial in drug resistant hairy cell leukemia A multi center phase 1 trial of HA22 in refectory ALL is open. Clinical activity with 6 complete remissions has been observed. The original trial in which patients were treated with 6 doses every 21 days is complete. An additional cohort has been added in which patients are being treated with additional doses. This study is in collaboration with Dr. Alan Wayne of the Pediatric Oncology Branch. Trials with LMB2 in ATL are ongoing. R. Kreitman is the lead investigator in those trials.Dr. Hassan has completed the trial in mesothelioma in which newly diagnosed patients receive SS1P and standard chemotherapy and observed an unexpectedly high response rate. Based on the high number of CRs at the MTD a randomized phase 2 trial is being planned. Another SS1P trial is ongoing in which patients receive pentostatin plus cyclophosphamide with SS1P to try and prevent neutralizing antibody formation allowing more doses to be given. Six patients have been treated and the results are encouraging. Roche has taken a license from NIH to develop and bring into clinical trials a new less immunogenic variant of SS1P described below.A significant advance is described publication in J Clinical Oncolgy (FILL IN) showing a very high complete and partial response rate in patients with chemo-refractory Hairy Cell leukemia. These results have caused Medimmune and CTEP to plan a pivotal trial to gain FDA approval to use Moxe in this patient population.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010020-17
Application #
8552637
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
2012
Total Cost
$1,166,535
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Chandramohan, Vidyalakshmi; Pegram, Charles N; Piao, Hailan et al. (2017) Production and quality control assessment of a GLP-grade immunotoxin, D2C7-(scdsFv)-PE38KDEL, for a phase I/II clinical trial. Appl Microbiol Biotechnol 101:2747-2766
Hassan, Raffit; Alewine, Christine; Pastan, Ira (2016) New Life for Immunotoxin Cancer Therapy. Clin Cancer Res 22:1055-8
Hassan, Raffit; Thomas, Anish; Alewine, Christine et al. (2016) Mesothelin Immunotherapy for Cancer: Ready for Prime Time? J Clin Oncol 34:4171-4179
Bao, Xuhui; Pastan, Ira; Bigner, Darell D et al. (2016) EGFR/EGFRvIII-targeted immunotoxin therapy for the treatment of glioblastomas via convection-enhanced delivery. Receptors Clin Investig 3:
Pastan, Ira; Hassan, Raffit (2014) Discovery of mesothelin and exploiting it as a target for immunotherapy. Cancer Res 74:2907-12
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
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
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

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