Hematologic/Blood Cancers
A Pilot Trial of WT1 Peptide-Loaded Allogeneic Dendritic Cell Vaccine and Donor Lymphocyte Infusion for WT1-Expressing Hematologic Malignancies
NCI-08-C-0051, NCT00923910
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Investigator(s): |
Alan S. Wayne, M.D.
Principal Investigator
Phone: 301-496-4256
Fax: 301-451-7010
waynea@mail.nih.gov
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Pediatric Oncology
Phone: 301-496-4256
1-877-624-4878 (Toll free)
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Background:
- Efforts to incorporate anti-tumor immunotherapy at stages of minimal residual disease (MRD) burden are limited by profound host immune depletion associated with standard anti-cancer therapies
- Allogeneic blood and marrow stem cell transplantation (SCT) can be curative for a number of hematologic malignancies
- Part of the success of this approach is an allogeneic immunologic reaction that has been demonstrated to play a role in the eradication of residual malignant disease after transplant in certain cancers (the so called graft-versus-leukemia [GVL] or graft-versus-tumor [GVT] effect); nonetheless, relapse remains the primary cause of treatment failure after allogeneic SCT
- The Wilms' tumor 1 (WT1) gene product is a tumor-associated antigen that represents a potential target for immunotherapy in a wide array of cancers
- WT1 is expressed in most cases of acute leukemia and in many cases of chronic myelogenous leukemia and myelodysplastic syndromes; it has limited expression in normal tissues beyond embryogenesis
- This trial represents an attempt to incorporate antigen-specific immunotherapy in the setting of allogeneic adoptive cell transfer
Objectives:
- Determine the safety, toxicity, and feasibility of donor-derived dendritic cell vaccination and donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation (SCT)
- Determine the frequency and severity of graft-versus-host disease (GVHD) in patients treated with peptide-loaded donor-derived dendritic cell vaccination and DLI
- Evaluate whether immunologic responses to Wilms' tumor 1 (WT1)-specific peptides can be generated by peptide-loaded donor-derived dendritic cell vaccination and DLI after allogeneic SCT
- Evaluate whether clinical responses to WT1-specific peptides can be generated by peptide-loaded donor-derived dendritic cell vaccination and DLI after allogeneic SCT
- Evaluate whether immunologic and/or clinical responses may be associated with the degree of WT1 expression by malignant cells or pre-existing donor anti-WT1 immunity
Key Eligibility Criteria:
- HLA-A2+ patients may be enrolled on this trial if they have relapsed or have residual disease following allogeneic stem cell transplantation (SCT) for a Wilms' tumor 1 (WT1) expressing hematologic malignancy
- Donors from the previous SCT, related or unrelated, must be 5- or 6- antigen genotypic HLA-matched (single HLA-A or B locus mismatch allowed) and HLAA2+
Study Outline:
- Pilot study, the primary aim of which is to assess safety and feasibility of a novel vaccine strategy aimed at enhancing the graft-versus-leukemia effect after allogeneic stem cell transplantation
- Donor-derived dendritic cells prepared from peripheral blood monocytes will be loaded with a combination of three Wilms' tumor 1 (WT1)-derived peptides
- These peptides are each WT1 comprised of one WT1-derived oligomeric epitope known to bind to HLA-A2 and an 11-mer protein transduction epitope known to enhance peptide loading and antigen presentation
- Patients will receive donor-derived dendritic cell vaccines every 14 days for six doses; three donor leukocyte infusions will also be administered with the vaccine every 28 days
- Study endpoints will include toxicity, feasibility, antigen-specific immunity, and disease response
- Up to 12 patients will be treated
- Stopping rules will take effect if excessive toxicity (e.g., graft-versus-host disease) or inability to generate vaccines is observed
Additional Information:
- This trial will be conducted at the NIH Clinical Center in Bethesda, MD. It is open to patients who meet the eligibility requirements, regardless of where they live in the United States.
- There is no charge for medical care received at NIH Clinical Center.
- FAQs about this study - provides information for patients about the trial such as frequency and duration of visits, costs, how to enroll, and study outline.
- PDQ (Physicians Data Query) - provides additional details about this study for health care providers.
Reviewed: 12/14/12
Updated: 12/2/11
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