Clinical trial NCT00145626
Conditions: Acute Myeloid Leukemia Acute Lymphocytic Leukemia Myelodysplasia Chronic Myeloid Leukemia Histiocytosis
Keywords: Stem cell transplantation Stem cell transplant Haploidentical transplant
Sponsor: St. Jude Children's Research Hospital
Start date: 2004-05-01; Completion date: 2016-07-01
Enrollment: 40 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Recent studies of conventional chemotherapy for infants with high-risk hematologic malignancies show that the long-term disease-free survival is low. Although blood and marrow stem cell transplantation using an HLA identical sibling has improved the outcome for these children, less than 25% have this donor source available. Another option is haploidentical transplantation using a partially matched family member donor (i.e. parental donor).

Although haploidentical transplantation has proven curative for some patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including infection and graft versus host disease (GVHD). Building on prior institutional trials, this study will provide patients a haploidentical graft depleted of T lymphocytes using the investigational device, CliniMACS selection system. One week after the transplant procedure, patients will also receive an infusion of additional donor derived white blood cells called Natural Killer (NK) cells in an effort to decrease risks for rejection of the graft, disease relapse, and regimen related toxicity. The primary objective of the study is to evaluate 1 year survival in infants with high risk hematologic malignancies who receive this study treatment.

Detailed description:
Secondary objectives for this study include the following:

* To estimate the incidence of three transplant-related adverse outcomes (i.e., regimen-related mortality, engraftment failure, and fatal acute GVHD) in the first 100 days after transplantation.
* To estimate the incidence of chronic graft-versus-host disease.
* To evaluate those factors that affect one-year survival.
* To assess the kinetics of lymphohematopoietic reconstitution.
* To assess the frequency and clinical relevance of minimal residual disease (MRD) before and after transplantation.
* To evaluate the incidence of and risk factors for long-term neurocognitive deficit and organ dysfunction.

Arms: arm 1: Participants who meet the eligibility criteria for this study. Donor cells will be obtained using the Miltenyi Biotec CliniMACS device.

Interventions: Chemotherapy and antibodies, allogeneic stem cell transplantation.
Interventions: intervention 1: Chemotherapy and antibodies intervention 2: Miltenyi Biotec CliniMACS intervention 3: Allogeneic stem cell transplantation
Intervention descriptions: intervention 1: Study participants will receive a non-TBI based preparative regimen consisting of Cyclophosphamide, fludarabine, thiotepa, melphalan, and muromonab-CD3 (OKT3) followed by an infusion of a T-lymphocyte depleted haploidentical hematopoietic stem cell graft. Seven days posttransplant, participants will receive an infusion of additional donor derived cells called NK cells. intervention 2: Stem cell selection device intervention 3: Allogeneic natural killer (NK)cell infusion

Protocol documents: