ZIC SC 010353 (ZIC) | |||
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Title | Experimental Therapeutics of Pediatric Hematopoietic Malignancies | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Wayne, Alan | NCI Program Director | N/A |
Cancer Activity | N/A | Division | CCR |
Funded Amount | $829,677 | Project Dates | 10/01/1999 - N/A |
Fiscal Year | 2011 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Bone Marrow Transplantation (50.0%) Cancer (100.0%) Childhood Cancers (90.0%) Organ Transplantation Research (50.0%) |
Childhood Leukemia (90.0%) Hodgkins disease (5.0%) Leukemia (90.0%) Non Hodgkins Lymphoma (5.0%) |
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Research Type | |||
Systemic Therapies - Discovery and Development Systemic Therapies - Clinical Applications |
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Abstract | |||
The Section leads novel clinical trials and conducts correlative biologic studies and pre-clinical investigations into the biology of leukemias and lymphomas in collaboration with intramural and extramural investigators. A major focus of the Hematologic Diseases Section research program is the development of targeted agents for childhood leukemias and lymphomas. Among the most active programs is the study of anti-CD22 immunotoxin agents RFB4(dsFv)-PE38 developed at the NCI in the therapy of drug-resistant acute lymphoblastic leukemia (ALL). A pediatric Phase I trial of a first-generation agent (BL22, CAT-3888) was conducted at the NCI (Wayne et al, Clin Cancer Res 2010;16:1894). BL22 was shown to have an acceptable safety profile and clinical activity was observed in children with multiply relapsed chemotherapy resistant ALL. Studies of a modified agent with higher CD22 binding affinity (moxetumomab pasudotox, HA22, CAT-8015) showed improved in vitro cytotoxicity against childhood ALL blasts (Mussai et al, Br J Haematol 2010, Epub ahead of print 2010 Jun 7, PMID: 20528877). A pediatric Phase I trial of HA22 is in progress at the NCI, St. Jude Childrens Research Hospital, and the Dana-Farber Cancer Institute/Childrens Hospital, Boston. Complete remissions in chemotherapy-refractory ALL have been achieved with this new agent (Wayne et al, Blood 2009;114(22):345a; Wayne et al, Blood 2010;116:3246a). Another major area of investigation is in allogeneic hematopoietic stem cell transplantation (AlloSCT) for pediatric leukemias and lymphomas. Relapse remains a major cause of failure of AlloSCT in the treatment of children and adolescents with leukemia. The Section investigates methods to direct allogeneic anti-cancer responses in attempt to enhance graft-versus-leukemia effects after AlloSCT. The Section also serves in a leadership role in a broad NCI program that addresses the problem of relapse after AlloSCT. These efforts include an NCI-sponsored International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation (Bishop et al, Biol Blood Marrow Transplant 2010;16:564) and specific studies of the natural history, biology, and treatment of relapse after AlloSCT. The clinical trial development activities of the Section are conducted in collaboration with a number of pediatric oncology consortia and cooperative groups including the Childrens Oncology Group and the Pediatric Blood and Marrow Transplant Consortium. |