Clinical trial NCT00145626: HLA-Nonidentical Stem Cell and Natural Killer Cell Transplantation for Children Less the Two Years of Age With Hematologic Malignancies
Official title: HLA-Nonidentical Stem Cell and Natural Killer Cell Transplantation for Children Less the Two Years of Age With Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Acute Lymphocytic Leukemia
Myelodysplasia
Chronic Myeloid Leukemia
Histiocytosis
Keywords: Stem cell transplantation
Stem cell transplant
Haploidentical transplant
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: Assisi Foundation
First posted: 2005-09-05
Enrollment: 40
Sex: ALL
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility 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

Primary outcomes:
measure: One-year Survival
timeFrame: One year after transplant
Secondary outcomes:
measure: Number of Transplant-Related Adverse Outcomes: Regimen-Related Mortality
timeFrame: 100 days post-transplantation
measure: Number of Transplant-Related Adverse Outcomes: Engraftment Failure
timeFrame: 100 days post-transplantation
measure: Number of Transplant-Related Adverse Outcomes: Fatal Acute Graft-Versus Host Disease (GVHD)
timeFrame: 100 days post-transplantation
measure: Number of Incidences of Chronic GVHD.
timeFrame: Up to 5 years after transplant
measure: Factors Affecting One-year Survival: Median Age of Donor at HSCT
timeFrame: Up to one year after transplant
measure: Factors Affecting One-year Survival: Median Dose of CD34
timeFrame: Up to one year after transplant
measure: Factors Affecting One-year Survival: Median Dose of NK Cells
timeFrame: Up to one year after transplant
measure: Factors Affecting One-year Survival: Disease Status at HSCT
timeFrame: Up to one year after transplant
measure: Factors Affecting One-year Survival: Donor Type
timeFrame: Up to one year after transplant
measure: Factors Affecting One-year Survival: Match N/6 HLA Loci
timeFrame: Up to one year after transplant
measure: Factors Affecting One-year Survival: Minimal Residual Disease (MRD)
timeFrame: Up to one year after transplant
measure: Incidence of and Risk Factors for Organ Dysfunction.
timeFrame: Up to 5 Years after transplant
measure: Incidence of and Risk Factors for Long-term Neurocognitive Deficit.
timeFrame: Up to 5 Years after transplant
measure: Frequency of and Clinical Relevance of Minimal Residual Disease (MRD) Before and After Transplantation
timeFrame: Baseline before HSCT, 1 year post HSCT, and up to 5 years post HSCT
measure: Kinetics of Lymphohematopoietic Reconstitution
timeFrame: From 0-3 months after HSCT through 4-5 years after HSCT
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Brandon Triplett, MD
role: PRINCIPAL_INVESTIGATOR
References: