This trial is active, not recruiting.

Conditions acute myeloid leukemia, acute lymphocytic leukemia, myelodysplasia, chronic myeloid leukemia, histiocytosis
Treatments chemotherapy and antibodies, miltenyi biotec clinimacs, allogeneic stem cell transplantation
Phase phase 2
Sponsor St. Jude Children's Research Hospital
Collaborator Assisi Foundation
Start date May 2004
End date March 2015
Trial size 40 participants
Trial identifier NCT00145626, INFT2, NCI-2011-03671


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
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.
chemotherapy and antibodies Cyclophosphamide
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.
miltenyi biotec clinimacs
Stem cell selection device
allogeneic stem cell transplantation Haploidentical stem cell transplantation
Allogeneic natural killer (NK)cell infusion

Primary Outcomes

One-year survival
time frame: One year after transplant

Secondary Outcomes

Number of transplant-related adverse outcomes
time frame: 5 Years
Number of incidences of chronic GVHD.
time frame: Up to 5 years after transplant
The factors that affect the one-year survival.
time frame: Up to one year after transplant
The kinetics of lymphohematopoietic reconstitution.
time frame: Up to 5 years after transplant
The frequency of and clinical relevance of minimal residual disease (MRD) before and after transplantation
time frame: Baseline and up to 5 years after transplant
The incidence of and risk factors for long-term neurocognitive deficit.
time frame: Up to 5 Years after transplant
The incidence of and risk factors for organ dysfunction.
time frame: Up to 5 Years after transplant

Eligibility Criteria

Male or female participants up to 24 months old.

Inclusion Criteria: Must have one of the following diagnosis: - AML in remission or relapse (e.g., FAB M7 or biphenotypic leukemia) - High-risk ALL in first remission (e.g., poor responder to prednisone, Ph+ ALL) - ALL beyond first remission - Secondary leukemia - Primary myelodysplasia (including RAEB, RAEB-T, CMML, JCML, and JMML) - Chronic myeloid leukemia - Histiocytoses (including multi-system Langerhans' cell histiocytosis and hemophagocytic lymphohistiocytosis Inclusion criteria Donor research participants - HIV negative (date). - Hepatitis B surface antigen negative (date). - Hepatitis C antibody negative (date). - Syphilis negative (date). - Donor is equal to or greater than 3 on 6 HLA match (date). - Not pregnant (negative pregnancy test). - Not lactating. - At least 18 years of age. Exclusion Criteria - Patients greater than 24 months of age at the time of transplant. - HLA-identical sibling donor is available. - Cardiac function: shortening fraction <25%. - Pulse oximetry oxygen saturation <92% on room air. - Glomerular filtration rate less than 40 ml/min/1.73 m2 (may use Technetium-99 result for GFR). - Direct bilirubin > 3 mg/dl. - SGPT > 500 U/L. - Patients with previous allergy to mouse proteins. - Patients with previous allergy to rabbit serum products. - Patients with Down's syndrome

Additional Information

Official title HLA-Nonidentical Stem Cell and Natural Killer Cell Transplantation for Children Less the Two Years of Age With Hematologic Malignancies
Principal investigator Wing H. Leung, M.D., PhD
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.
Trial information was received from ClinicalTrials.gov and was last updated in May 2015.
Information provided to ClinicalTrials.gov by St. Jude Children's Research Hospital.