Acute Myeloid Leukemia Clinical Trial
Official title:
A Phase II Study of Preemptive Fast Withdrawal of Immunosuppression and Donor Lymphocyte Infusions for Achieving Complete Donor Chimerism Following Allogeneic Transplant for Pediatric Hematologic Malignancies
There is no curative therapy once acute leukemia patients relapse after transplant. Patients who develop clinically significant graft versus host disease (GVHD) have a lower rate of relapse than those who do not develop GVHD. We are initiating this study of post-transplant fast withdrawal of immunosuppression and donor lymphocyte infusions, with a goal of achieving full donor chimerism in children with hematologic malignancies. If our hypothesis that full donor chimerism results in leukemia-free survival is correct, using immune modulation to achieve full donor chimerism should decrease relapse rate and thus increase survival. The goal of this Phase II study is to identify if achieving full donor chimerism in whole blood CD3+ and leukemia-specific (CD14/15+, CD19+, CD33+ and CD34+) subset may decrease the risk of relapse of patients undergoing allogeneic transplant for hematologic malignancy.
Status | Active, not recruiting |
Enrollment | 43 |
Est. completion date | July 2015 |
Est. primary completion date | July 2014 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 6 Months to 25 Years |
Eligibility |
Inclusion Criteria: - Age 6 months - 25 years. - Diagnoses of acute leukemia (AML, ALL, biphenotypic leukemia), pre-leukemic syndromes (monosomy 7 or other bone marrow clonal malformations), JMML, myelodysplastic syndromes or CML. - Undergoing an allogeneic transplant as standard care. - Performance status: Karnofsky/Lansky>60%. - Availability of pre-transplant recipient's DNA and donor's DNA for chimerism testing. This could be DNA or material from which DNA could be extracted. Frozen blood would be preferred. For some patients, post transplant specimens that are not infiltrated with donor cells may be used. - Bone marrow or PBMTC as stem cell source.HLA matching: donor and recipient should be matched at a minimum of 7/8 antigens (A,B,C and DrB1) for bone marrow and PBMTC transplants. - No history of =grade III acute GVHD. Exclusion Criteria: - Treatment on other experimental protocols, if withdrawal of immunosuppression interferes with procedures of follow-up on the primary study. - Leukemia relapse defined as > 5% blasts on bone marrow exam or >1% leukemia cells by immunoflow MRD, or presence of extramedullary leukemia. - History of acute GVHD = stage III or with any degree of active acute or cGVHD. - On steroids for any reason. - Any condition that compromises compliance with the objectives and procedures of this protocol, as judged by the principal investigator. - Cells for DLI cannot be obtained from the donor. |
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | University of California | San Francisco | California |
United States | All Children's Hospital | St. Petersburg | Florida |
Lead Sponsor | Collaborator |
---|---|
University of California, San Francisco | All Children’s Hospital Johns Hopkins Medicine |
United States,
Horn B, Soni S, Khan S, Petrovic A, Breslin N, Cowan M, Pelle-Day G, Cooperstein E, Baxter-Lowe LA. Feasibility study of preemptive withdrawal of immunosuppression based on chimerism testing in children undergoing myeloablative allogeneic transplantation for hematologic malignancies. Bone Marrow Transplant. 2009 Mar;43(6):469-76. doi: 10.1038/bmt.2008.339. Epub 2008 Oct 27. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Relapse at 2 Years Post-transplant. | Definition of relapse was >5 % blasts in bone marrow | 2 years post transplant. | No |
Secondary | 2 Years Post-transplant Survival. | 2 years post transplant | Yes | |
Secondary | The Incidence of Acute Graft Versus Host Disease (aGVHD). | Definition and diagnostic criteria of aGVHD according to: 1994 Consensus Conference on Acute GVHD Grading. Przepiorka D1, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. Bone Marrow Transplant. 1995 Jun;15(6):825-8. In this system, patients are divided into one of four grades (I-IV) depending on the degree, or stage, of involvement in three organs. The skin is staged with percent body surface involved, the liver is staged with degree of bilirubin elevation, and the gastrointestinal tract is staged with amount of diarrhea. |
2 years post transplant | Yes |
Secondary | The Incidence of Chronic GVHD (cGVHD). | Diagnostic criteria of cGVHD from: Filipovich AH, Weisdorf D, Pavletic S et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-host disease: I Diagnosis and Staging Working Group Report. Biology of Blood and Marrow Transplantation 2005;11:945-955. The diagnosis of chronic GVHD requires the following: 1) Distinction from acute GVHD; 2) Presence of at least 1 diagnostic clinical sign of chronic GVHD or presence of at least 1 distinctive manifestation confirmed by pertinent biopsy or other relevant tests; 3) Exclusion of other possible diagnoses. Scoring of organ manifestations requires careful assessment of signs, symptoms, laboratory values, and other study results. A clinical scoring system (0-3) is used for evaluation of the involvement of individual organs and sites. Global assessment of severity (mild, moderate, or severe) is derived by combining organ- and site-specific scores. |
2 years post transplant | Yes |
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