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| Name | Class |
|---|---|
| Cellect Biotechnology | INDUSTRY |
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Finding a donor remains a challenge for patients in need of an urgent hematopoietic stem cell transplantation (HSCT). The ability to obtain half matched stem cells from any family member represents a significant breakthrough in the field. Haploidentical haplo-HSCT is characterized by the nearly uniform and immediate availability of a donor and the availability of the donor for post-transplant cellular immunotherapy. However, haplo-HSCT has a high risk of Graft versus Host Disease (GvHD) and poor immune reconstitution when GvHD is prevented by all existing methods of vigorous ex vivo or in vivo T-cell depletion. Different treatment approaches are currently being explored to mitigate complications such as graft rejection, severe GvHD, and prolonged immune suppression. Novel experimental utilization of T regulatory cells, alloreactive natural killer (NK) cells, and other T cell subsets hold great promise. Cellect Biotherapeutics' platform technology, ApoGraft, is based on the findings that GvHD can be prevented by Fas receptor mediated selective depletion of T cell subsets, ex vivo. The investigators hypothesize that the use of ApoGrafts for haplo-HSCT will be safe, and reduce rates of GVHD without affecting Graft-versus-Leukemia (GvL).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Recipient | Experimental |
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| Donor | No Intervention | -Donors will undergo apheresis from peripheral blood after daily G-CSF administration (for up to 5 days prior to Day -1) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ApoGraft | Drug | ApoGraft is a cell based product, manufactured with mobilized peripheral blood. |
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| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability of ApoGraft as measured by adverse events related to ApoGraft product | -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting. | From day 0 to 1 year post-transplantation of ApoGraft product |
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative incidence of graft failure | -Failure to engraft will be defined as failure to achieve absolute neutrophil count > 500 for 3 days by Day 35 | 35 days post haplo-HCT |
| Treatment related mortality |
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Recipient Inclusion Criteria:
Adult male or female subjects, 18-70 years of age.
Availability of an HLA-haploidentical-HSCT related donor with a minimum match of 5/10 at the HLA A, B, C, DR and DQ loci.
Hematologic malignancy in remission or controlled as below:
ECOG performance status score 0-1 at time of the screening visit
Cardiac left ventricular ejection fraction ≥ 40% in adults within 90 days of start of lymphodepleting chemotherapy
Pulmonary function test with DLCO, FEV1 and FVC of ≥ 50% within 90 days of start of lymphodepleting chemotherapy.
Oxygen saturation ≥ 90% on room air at screening visit.
Subjects must have adequate organ function as defined below within 2 weeks of Day 0:
If female of childbearing potential, agree to use an acceptable method of birth control or be surgically sterile, and have a negative pregnancy test.
Available HLA-haploidentical donor
Must be able to receive GvHD prophylaxis with tacrolimus, mycophenolate mofetil, and cyclophosphamide
Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable). Subjects requiring a guardian to sign informed consent will not be included.
Recipient Exclusion Criteria:
Donor Inclusion Criteria
Adult male or female subjects, 18-65 years of age.
Donor criteria according to standard NMDP criteria for donor selection.
Fit to receive G-CSF and donate peripheral blood stem cells.
Able to sign written informed consent including consent for 2nd donation in the event of graft failure in the recipient.
Donor Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Mark Schroeder, M.D. | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
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| Label | URL |
|---|---|
| Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine | View source |
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The first three recipients will be treated in a sequential manner meaning that subjects will be transplanted with ApoGraft only after the engraftment of the previous subject has occurred.
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-Death that results from a transplant procedure-related complication (e.g. infection, organ failure, hemorrhage, GVHD) rather than from relapse of the underlying disease or an unrelated cause.
| Through 1 year post-transplantation of ApoGraft product |
| Time of neutrophil engraftment as determined by number of days for reaching first of 3 consecutive days with ANC ≥ 500/mm3 | 35 days post haplo-HCT |
| Rate of neutrophil engraftment as determined by number of days for reaching first of 3 consecutive days with ANC ≥ 500/mm3 | 35 days post haplo-HCT |
| Time of platelet engraftment determined by number of days for reaching first measurement of 3 consecutive measurements with platelets ≥ 20,000/mm3 in the absence of platelet administration during the prior 7 days | 35 days post haplo-HCT |
| Rate of platelet engraftment determined by number of days for reaching first measurement of 3 consecutive measurements with platelets ≥ 20,000/mm3 in the absence of platelet administration during the prior 7 days | 35 days post haplo-HCT |
| Incidence of Grade 2-4 acute GVHD | -Acute GVHD will be assessed using MAGIC criteria | Day 180 |
| Time to development of Grade 2-4 acute GVHD | -Acute GVHD will be assessed using MAGIC criteria | Day 180 |
| Incidence of Grade 3-4 acute GVHD | -Acute GVHD will be assessed using MAGIC criteria | Day 180 |
| Time to development of Grade 3-4 acute GVHD | -Acute GVHD will be assessed using MAGIC criteria | Day 180 |