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

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:

Genetics Home Reference related topics: familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Acute Myeloid Leukemia Cancer Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Leukemia Myelodysplastic Syndromes

Drug Information available for: Cyclophosphamide Thiotepa Melphalan Melphalan hydrochloride Fludarabine Fludarabine phosphate Muromonab-cd3

U.S. FDA Resources

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 2014
Estimated Primary Completion Date:	May 2014 (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

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

Investigators

Principal Investigator:

Wing H. Leung, M.D., PhD

St. Jude Children's Research Hospital

More Information

Additional Information:

St. Jude Children's Research Hospital This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:	NCT00145626 History of Changes
Other Study ID Numbers:	INF-T2
Study First Received:	September 1, 2005
Last Updated:	January 9, 2013
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
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
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
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents

ClinicalTrials.gov processed this record on May 19, 2013