Mismatched Family Member Donor Transplantation for Children and Young Adults With High Risk Hematological Malignancies
Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor.
Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including GVHD and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection.
For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell dose that will reduce the risk for GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution and graft integrity. Building on prior institutional trials, this study will provide patients with a haploidentical (HAPLO) graft engineered to specific T cell target values using the CliniMACS system. A reduced intensity, preparative regimen will be used in an effort to reduce regimen-related toxicity and mortality.
The primary aim of the study is to help improve overall survival with haploidentical stem cell transplant in this high risk patient population by 1) limiting the complication of graft versus host disease (GVHD), 2) enhancing post-transplant immune reconstitution, and 3) reducing non-relapse mortality.
Leukemia, Acute Lymphocytic (ALL)
Leukemia, Myeloid, Acute(AML)
Leukemia, Myeloid, Chronic(CML)
Juvenile Myelomonocytic Leukemia (JMML)
Hemoglobinuria, Paroxysmal Nocturnal (PNH)
Lymphoma, Non-Hodgkin (NHL)
Myelodysplastic Syndrome (MDS)
Procedure: Stem cell transplantation
Drug: Systemic chemotherapy and antibodies
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Reduced Intensity Conditioning Regimen With CD3-Depleted Hematopoietic Stem Cells to Improve Survival for Patients With Hematologic Malignancies Undergoing Haploidentical Stem Cell Transplantation|
- To determine if one year event-free survival can be improved in pediatric patients undergoing a haploidentical transplant by using a reduced intensity conditioning regimen and a targeted dose T cell depleted donor product. [ Time Frame: one year post-transplant ] [ Designated as safety issue: Yes ]
- To estimate the one-year overall survival (OS) and disease-free survival (DFS) for research participants who receive this study treatment. [ Time Frame: one year post-transplant ] [ Designated as safety issue: No ]
- To estimate the cumulative incidence of relapse for research participants who receive this study treatment. [ Time Frame: three years post-transplant ] [ Designated as safety issue: No ]
- To estimate the rate of overall grade III-IV acute GVHD, and the rate and severity of chronic GVHD in research participants. [ Time Frame: three years post-transplant ] [ Designated as safety issue: No ]
- To estimate the incidence of non-hematologic regimen-related toxicity and regimen-related mortality in the first 100 days post-transplant. [ Time Frame: 100 days post-transplant ] [ Designated as safety issue: No ]
|Study Start Date:||November 2007|
|Estimated Study Completion Date:||January 2018|
|Estimated Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
Experimental: High-Risk Hematologic Malignancies
Participants meeting eligibility criteria undergo haploidentical stem cell transplantation along with systemic chemotherapy and antibodies.
Grafts from suitable haploidentical donors are processed using the CliniMACS system.
Miltenyi Biotec CliniMACS stem cell selection deviceProcedure: Stem cell transplantation
An infusion of HLA mismatched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device.Drug: Systemic chemotherapy and antibodies
Transplant recipients will receive a conditioning regimen consisting of the following:
Hematopoietic stem cell [HSC infusion]
Granulocytic colony stimulating factor [G-CSF]
This study will explore the following objectives:
- To assess if the event-free survival at one-year post-transplant for research participants with high-risk hematologic malignancies can be improved following HAPLO hematopoietic stem cell transplant (HSCT) using a graft depleted of CD3+ cells ex vivo and a reduced intensity-conditioning regimen.
- To estimate the one-year overall survival (OS) and disease-free survival (DFS) for research participants who receive this study treatment.
- To estimate the cumulative incidence of relapse for research participants who receive this study treatment.
- To estimate the rate of overall grade III-IV acute GVHD, and the rate and severity of chronic GVHD in research participants.
- To estimate the incidence of non-hematologic regimen-related toxicity and regimen-related mortality in the first 100 days post-transplant.
- To explore the biologic significance of soluble interleukin-2 receptor and immunologic state [quantitative lymphocyte studies, V beta spectratyping, T-cell receptor excision circles (TREC) assay] to predict the development of acute and chronic GVHD in these research participants.
- To measure the pharmacokinetics of Campath-1H in pediatric HAPLO HSCT recipients
Please refer to this study by its ClinicalTrials.gov identifier: NCT00566696
|Contact: Brandon Triplett, MDfirstname.lastname@example.org|
|United States, Tennessee|
|St. Jude Children's Research Hospital||Recruiting|
|Memphis, Tennessee, United States, 38105|
|Contact: Brandon Triplett, MD 866-278-5833 email@example.com|
|Principal Investigator: Brandon Triplett, MD|
|Principal Investigator:||Brandon Triplett, MD||St. Jude Children's Research Hospital|