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Sponsored by: |
St. Jude Children's Research Hospital |
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Information provided by: | St. Jude Children's Research Hospital |
ClinicalTrials.gov Identifier: | NCT00145613 |
Relapsed disease is the most common cause of death in children with hematological malignancies. Patients who fail high-intensity conventional chemotherapeutic regimens or relapse after stem cell transplantation have a poor prognosis. Toxicity from multiple therapies and elevated leukemic/tumor burden usually make these patients ineligible for the aggressive chemotherapy regimens required for conventional stem cell transplantation. Alternative options are needed. One type of treatment being explored is called haploidentical transplant.
Conventional blood or bone marrow stem cell transplant involves destroying the patient's diseased marrow with radiation or chemotherapy. Healthy marrow from a donor is then infused into the patient where it migrates to the bone marrow space to begin generating new blood cells. The best type of donor is a sibling or unrelated donor with an identical immune system (HLA "match"). However, most patients do not have a matched sibling available and/or are unable to identify an acceptable unrelated donor through the registries in a timely manner. In addition, the aggressive treatment required to prepare the body for these types of transplants can be too toxic for these highly pretreated patients. Therefore doctors are investigating haploidentical transplant using stem cells from HLA partially matched family member donors.
Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including graft versus host disease (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 patient's (the host) body tissues 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 infection. However, the presence of T cells in the graft may offer a positive effect called graft versus malignancy or GVM. With GVM, the donor T cells recognize the patient's malignant cells as diseased and, in turn, attack these diseased cells.
For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell depleted product to reduce the risk of GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution, graft integrity and GVM.
In this study, patients were given a haploidentical graft engineered to with specific T cell parameter values using the CliniMACS system. A reduced intensity, preparative regimen was used to reduce regimen-related toxicity and mortality. The primary goal of this study is to evaluate overall survival in those who receive this study treatment.
Condition | Intervention | Phase |
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Acute Lymphoblastic Leukemia (ALL) Acute Myeloid Leukemia (AML) Secondary AML Myelodysplastic Syndrome (MDS) Secondary MDS Chronic Myeloid Leukemia Juvenile Myelomonocytic Leukemia (JMML) Paroxysmal Nocturnal Hemoglobinuria (PNH) Lymphoma, Non-Hodgkin Hodgkin Disease |
Procedure: Stem Cell Transplantation Device: Miltenyi Biotec CliniMACS Drug: Systemic chemotherapy and antibodies |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study |
Official Title: | Haploidentical Stem Cell Transplantation Utilizing T-Cell Depletion as Therapy for Patients With Refractory Hematological Malignancies |
Enrollment: | 25 |
Study Start Date: | June 2003 |
Estimated Study Completion Date: | March 2010 |
Primary Completion Date: | July 2006 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1 |
Procedure: Stem Cell Transplantation
An infusion of HLA mismatched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device.
Device: Miltenyi Biotec CliniMACS
stem cell selection device
Drug: Systemic chemotherapy and antibodies
Transplant recipients received a non-TBI based reduced intensity conditioning regimen consisting of OKT-3, Fludarabine Thiotepa, and Melphalan. Rituximab was administered within 24 hours of the transplant in an effort to prevent PTLPD. In addition to T-cell depletion of the haploidentical stem cell product, Mycophenolate mofetil was provided as prophylaxis for GVHD.
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Secondary objectives for this protocol are to 1) assess the kinetics of lymphohematopoietic reconstitution and 2) describe the short and long-term (up to 5 years post- transplant) toxicity of haploidentical stem cell transplantation, including GVHD, in children with refractory hematological malignancies.
Ages Eligible for Study: | 2 Years to 21 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria: Refractory hematological malignancies (chemoresistant relapse or primary induction failure) including:
Hodgkin's Disease (HD)*
*Patients with lymphomas must have failed standard non-cross reactive combination salvage chemotherapy with or without radiation therapy followed by autologous stem cell transplant or patients with chemo resistant disease
Exclusion Criteria:
United States, Tennessee | |
St. Jude Children's Research Hospital | |
Memphis, Tennessee, United States, 38105 |
Principal Investigator: | Gregory Hale, M.D. | St. Jude Children's Research Hospital |
Responsible Party: | St. Jude Children's Research Hospital ( Gregory Hale, M.D. / Principal Investigator ) |
Study ID Numbers: | REFSCT |
Study First Received: | September 1, 2005 |
Last Updated: | May 16, 2008 |
ClinicalTrials.gov Identifier: | NCT00145613 |
Health Authority: | United States: Food and Drug Administration |
Haploidentical stem cell transplant High risk hematologic malignancies Allogeneic stem cell transplant Mismatched family member stem cell donor |
Juvenile myelomonocytic leukemia Chronic myelogenous leukemia Chronic myelomonocytic leukemia Hodgkin lymphoma, adult Preleukemia Mycophenolate mofetil Neoplasm Metastasis Hodgkin Disease Immunoglobulins Myelodysplastic syndromes Immunoproliferative Disorders Precursor Cell Lymphoblastic Leukemia-Lymphoma Hematologic Diseases Rituximab Leukemia, Myelomonocytic, Chronic |
Myeloproliferative Disorders Acute myelogenous leukemia Anemia, Hemolytic Leukemia, Myeloid Thiotepa Myelodysplastic myeloproliferative disease Proteinuria Fludarabine Lymphoma, Non-Hodgkin Paroxysmal nocturnal hemoglobinuria Melphalan Leukemia, Lymphoid Hodgkin's disease Hematologic Neoplasms Precancerous Conditions |
Urological Manifestations Neoplastic Processes Neoplasms Neoplasms by Site |
Pathologic Processes Neoplasms by Histologic Type Immune System Diseases |