Hematologic Malignancy, Other Hematologic Condition, Pediatric Patients
Conditions
Keywords
Donor, granulocyte stimulating factor (GCSF), apheresis
Brief summary
This is an open label, interventional, non-randomized, phase II trial of TCR alpha/beta and CD19-depeleted allogeneic HCT in pediatric patients with hematologic disease.
Detailed description
This is a single-site, open label, interventional, non-randomized, phase II trial of TCRαβ/CD19 deplete allogeneic HCT as donor source and sole GVHD prophylaxis in pediatric patients with either malignant or non-malignant hematologic disease who are eligable for allogeneic HCT, but lack a HLA-matched sibling donor.
Interventions
DEVICECliniMACS Plus Instrument
Miltenyi Biotec's CliniMACS Plus Instrument is to be used to TCRαβ CD19 deplete products utilized in this protocol. The CliniMACS Plus is an automated cell separation platform which is functionally closed, maintaining a sterile system for cell depletion and enrichment utilizing a magnetic separation column. Reagents and supplies are to be used for research only but are manufactured and tested under a quality system certified to ISO 13485. Should CD34 selection be required to augment stem cell dose, Miltenyi Biotec's CliniMACS® Plus CD34 Reagent System is FDA approved as a Humanitarian Use Device (HUD). The approved indication was the treatment of patients with acute myeloid leukemia (AML) undergoing myeloablative transplant from matched related allogeneic donors. The CliniMACS® Plus reagent system was approved to obtain an enriched CD34+ cell population for hematopoietic reconstitution without the need for GVHD prophylaxis.
Sponsors
University of Colorado, Denver
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Eligible Patients with a hematologic disease who could benefit from HCT with an eligible mismatched related or unrelated donor per donor selection criteria. Patient/recipient admitted of HCT/start of preparative regimen and stem cell infusion
Eligibility
Sex/Gender
ALL
Age
31 Days to 30 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 31 days to \<30 years 2. Have a malignant or non-malignant hematologic disease, defined as disease resulting from abnormal function of a cell of the hematopoietic stem cell lineage, that could benefit from an allogeneic HCT. Examples include acute and chronic leukemias, myelodysplastic syndrome, lymphoma, severe acquired and congenital cytopenias/marrow failure, white blood cell abnormalities, red blood cell abnormalities, and platelet abnormalities. 3. Clinical remission for patients with acute leukemia (MDS/AML excluded) or lymphoma 4. Lack a healthy and willing HLA-identical related donor, with the exception of patients with FA who will be eligible with a willing HLA-identical related donor given the standard use of T-cell depletion in matched sibling donor HCT in FA 5. Have a related or an unrelated donor who meets the donor selection criteria, is healthy, willing, and able to receive GCSF with or without Plerixafor, and undergo apheresis through placement of catheters in the antecubital veins or a temporary central venous catheter 6. Able to give informed consent if ≥ 18 years, or with legal guardian capable of giving informed consent if \< 18 years 7. Provision of signed and dated informed consent form
Exclusion criteria
1. Uncontrolled, active infection at time of HCT 2. HIV positivity 3. Cardiac ejection fraction \<45% 4. Creatinine clearance \<60 mL/min/1.72 mL 5. Pulmonary diffusion capacity (adjusted for hemoglobin), FEV1, or FVC \<60% of predicted or an O2 saturation \<94% on room air if unable to perform pulmonary function testing 6. Serum ALT \>5x upper limit of normal or bilirubin \>2 7. Performance score (Lansky or Karnofsky) \<50 8. Pregnant or lactating females, as many medications necessary for a successful HCT are potentially harmful to unborn babies and infants.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of severe (grade III-IV) acute graft-versus-host disease (GVHD) at day 100 after infusion of a TCRαβ+/CD19+ negative, peripheral blood stem cell (PBSC) product without additional GVHD prophylaxis. | 5 years | Grade to be determined using Acute GVHD Staging Scale |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with relapse | 1 year | Interval from transplant to relapse/recurrence of disease |
| Number of treatment-related mortality (TRM) | 1 year | Defined as death due to regimen-related toxicity or GVD. |
| Disease-free Survival (DFS) measured in days | 1 year | Defined as the minimum time interval from transplant to relapse/recurrence of disease, death or last follow-up. |
| Number of patients with non-engraftment | 100 days | Defined as the lack of donor-derived neutrophil engraftment |
| Immune Reconstitution | 1 year | Incidence of absolute CD4+ T-cell count \>400 cells at 1 year post-HCT |
| Post-HCT infections | 100 days | Incidence of bacterial, fungal, and viral infections at day +100 |
| Overall Survival (OS) measured in days | 1 year | Determined at 1 year post-HCT |
Outcome results
None listed