NCT00145626

HLA-Nonidentical Stem Cell and Natural Killer Cell Transplantation for Children Less the Two Years of Age With Hematologic Malignancies

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 24 Months
• Healthy volunteers: Not accepted

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.

Conditions

• Acute Myeloid Leukemia
• Acute Lymphocytic Leukemia
• Myelodysplasia
• Chronic Myeloid Leukemia
• Histiocytosis

Interventions

Type	Name	Description
DRUG	Chemotherapy and antibodies	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.
DEVICE	Miltenyi Biotec CliniMACS	Stem cell selection device
PROCEDURE	Allogeneic stem cell transplantation	Allogeneic natural killer (NK)cell infusion

Timeline

• Start date: 2004-05-01
• Primary completion: 2015-03-01
• Completion: 2016-07-01
• First posted: 2005-09-05
• Last updated: 2017-06-19
• Results posted: 2015-12-14

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated device study