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.
Verified January 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: January 16, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
Acute Lymphocytic Leukemia
Myelodysplasia
Chronic Myeloid Leukemia
Histiocytosis
Drug: Chemotherapy and antibodies
Device: Miltenyi Biotec CliniMACS
Procedure: Allogeneic stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: HLA-Nonidentical Stem Cell and Natural Killer Cell Transplantation for Children Less the Two Years of Age With Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 66
Study Start Date: May 2004
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

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.
  Eligibility

Ages Eligible for Study:   up to 24 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00145626

Contacts
Contact: Wing H. Leung, M.D., PhD 1-866-278-5833 info@stjude.org

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Wing H. Leung, M.D., PhD    866-278-5833    info@stjude.org   
Principal Investigator: Wing H. Leung, M.D., PhD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Assisi Foundation
Investigators
Principal Investigator: Wing H. Leung, M.D., PhD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00145626     History of Changes
Other Study ID Numbers: INFT2
Study First Received: September 1, 2005
Last Updated: January 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by St. Jude Children's Research Hospital:
Stem cell transplantation
Stem cell transplant
Haploidentical transplant

Additional relevant MeSH terms:
Histiocytosis
Histiocytosis, Langerhans-Cell
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Myelodysplastic Syndromes
Preleukemia
Hematologic Neoplasms
Lymphatic Diseases
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms by Site
Antibodies
Cyclophosphamide
Melphalan
Thiotepa
Fludarabine

ClinicalTrials.gov processed this record on April 17, 2014