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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by St. Jude Children's Research Hospital
Sponsor:
Collaborator:
Assisi Foundation
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00145626
First received: September 1, 2005
Last updated: July 14, 2014
Last verified: July 2014

September 1, 2005
July 14, 2014
May 2004
May 2016   (final data collection date for primary outcome measure)
To evaluate the one-year survival of infants with high-risk hematologic malignancies who receive a haploidentical transplant procedure using a non-TBI based preparative regimen and T-lymphocyte depleted graft with a subsequent infusion of donor NK cells. [ Time Frame: 5 Years ] [ Designated as safety issue: Yes ]
  • To find out the effects (good and bad) of treatment with stem cell and NK cell transplant
  • To study the outcome of very young subjects treated with stem cell and NK cell transplant one year after treatment
  • To find out what factors affect the outcome of very young subjects treated with stem cell and NK cell transplant
  • To study the blood cells in the bone marrow before and after treatment with stem cell and NK cell transplant
Complete list of historical versions of study NCT00145626 on ClinicalTrials.gov Archive Site
  • To estimate the incidence of 3 transplant-related adverse outcomes, i.e., regimen-related mortality, engraftment failure, and fatal acute GVHD in the first 100 days after hematopoietic stem cell (HSC) transplantation. [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
  • To estimate the incidence of chronic GVHD. [ Time Frame: 5 Years ] [ Designated as safety issue: Yes ]
  • To evaluate the factors that affect the one-year survival. [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
  • To assess the kinetics of lymphohematopoietic reconstitution. [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
  • To assess the frequency and clinical relevance of minimal residual disease (MRD) before and after transplantation [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
  • To evaluate the incidence of and risk factors for long-term neurocognitive deficit and organ dysfunction. [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
HLA-Nonidentical Stem Cell and Natural Killer Cell Transplantation for Children Less the Two Years of Age With Hematologic Malignancies
HLA-Nonidentical Stem Cell and Natural Killer Cell Transplantation for Children Less the Two Years of Age With Hematologic Malignancies

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.

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.
Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acute Myeloid Leukemia
  • Acute Lymphocytic Leukemia
  • Myelodysplasia
  • Chronic Myeloid Leukemia
  • Histiocytosis
  • 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.
    Other Names:
    • Cyclophosphamide
    • Fludarabine
    • Thiotepa
    • Melphalan
    • OKT3
  • Device: Miltenyi Biotec CliniMACS
    Stem cell selection device
  • Procedure: Allogeneic stem cell transplantation
    Allogeneic natural killer (NK)cell infusion
    Other Names:
    • Haploidentical stem cell transplantation
    • Allogeneic stem cell transplant
    • Immunotherapy
    • Mismatched family member donor transplant
    • NK cell infusions
Experimental: Study Participants

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:
  • Drug: Chemotherapy and antibodies
  • Device: Miltenyi Biotec CliniMACS
  • Procedure: Allogeneic stem cell transplantation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
66
May 2016
May 2016   (final data collection date for primary outcome measure)

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
Both
up to 24 Months
No
Contact: Wing H. Leung, M.D., PhD 1-866-278-5833 info@stjude.org
United States
 
NCT00145626
INFT2
No
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
Assisi Foundation
Principal Investigator: Wing H. Leung, M.D., PhD St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP