Phase 2
N=19
HLA-Nonidentical Stem Cell and Natural Killer Cell Transplantation for Children Less the Two Years of Age With Hematologic Malignancies
Acute Myeloid Leukemia · Acute Lymphocytic Leukemia · Myelodysplasia · Chronic Myeloid Leukemia · Histiocytosis
Bottom Line
View on ClinicalTrials.gov: NCT00145626 ↗Enrolled (actual)
19
Serious AEs
93.8%
Results posted
Dec 2015
Primary outcome: Primary: One-year Survival — 50 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Chemotherapy and antibodies (Drug); Miltenyi Biotec CliniMACS (Device); Allogeneic stem cell transplantation (Procedure)
- Age
- Pediatric
- Sex
- All
- Sponsor
- St. Jude Children's Research Hospital
- Primary completion
- Mar 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY One-year Survival |
50 | — |
| SECONDARY Number of Transplant-Related Adverse Outcomes: Regimen-Related Mortality |
3 | — |
| SECONDARY Number of Transplant-Related Adverse Outcomes: Engraftment Failure |
0.286 | — |
| SECONDARY Number of Transplant-Related Adverse Outcomes: Fatal Acute Graft-Versus Host Disease (GVHD) |
— | — |
| SECONDARY Number of Incidences of Chronic GVHD. |
0; 1; 13 | — |
| SECONDARY Factors Affecting One-year Survival: Median Age of Donor at HSCT |
21.5; 27.2; 25.73 | — |
| SECONDARY Factors Affecting One-year Survival: Median Dose of CD34 |
35.2; 38.3; 37.8 | — |
| SECONDARY Factors Affecting One-year Survival: Median Dose of NK Cells |
40.2; 37.6; 38.9 | — |
| SECONDARY Factors Affecting One-year Survival: Disease Status at HSCT |
0; 1; 1; 6; 2; 8 | — |
| SECONDARY Factors Affecting One-year Survival: Donor Type |
2; 4; 6; 5; 2; 7 | — |
| SECONDARY Factors Affecting One-year Survival: Match N/6 HLA Loci |
6; 3; 9; 1; 4; 5 | — |
| SECONDARY Factors Affecting One-year Survival: Minimal Residual Disease (MRD) |
2; 1; 3; 1; 0; 1 | — |
| SECONDARY Incidence of and Risk Factors for Organ Dysfunction. |
— | — |
| SECONDARY Incidence of and Risk Factors for Long-term Neurocognitive Deficit. |
— | — |
| SECONDARY Frequency of and Clinical Relevance of Minimal Residual Disease (MRD) Before and After Transplantation |
1; 1; 1; 0; 0; 0 | — |
| SECONDARY Kinetics of Lymphohematopoietic Reconstitution |
0.22; 0.57; 1.15; 2.24; 1.65; 2.88 | — |
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.
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 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
Data sourced from ClinicalTrials.gov (NCT00145626). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.