Haploidentical CD34+ Selected Cells Combined With Single Unit Umbilical Cord Blood Transplant for Treatment of High-risk Hematologic Disorders

Study Overview
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Brief Summary
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This is a study to evaluate the safety and efficacy of Miltenyi CliniMACS® CD34 Reagent System to promote engraftment of haploidentical CD34+ selected cells combined with single unit umbilical cord blood transplant for treatment of high-risk hematologic disorders.

Detailed Description
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In this clinical protocol, the CliniMACS® CD34 Reagent System will be used for processing hematopoietic progenitor cells collected by apheresis (HPC, Apheresis) from an allogeneic, HLA-haploidentical, related donor to obtain a CD34+ cell-enriched population for hematopoietic reconstitution. The haploidentical donor will be mobilized by G-CSF and undergo one apheresis to collect CD34+ stem cells. The products will be cryopreserved until the time of transplantation. Recipients with hematologic disorders who require transplant will receive a standard conditioning regimen and will receive an allograft on day 0 containing donor CD34+ cells that have been positively selected and T-cell depleted following G-CSF mobilization combined with a single UCB unit.

Official Title
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Safety and Efficacy of Miltenyi CliniMACS® CD34 Reagent System for Transplant Protocol Utilizing Haploidentical CD34+ Selected Cells Combined With Single Unit Umbilical Cord Blood Transplant for Treatment of High-risk Hematologic Disorders

Conditions
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Hematologic Disorders

Intervention / Treatment
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* Device: Miltenyi CliniMACS® CD34 Reagent System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria - Recipient Ages 18-80 years inclusive Diagnosed with high risk hematologic disorders warranting stem cell transplant per institutional standard of care Lack HLA-identical related donor Availability of at least one HLA- haploidentical (i.e. => 5/10 and <= 8/10 HLA match) related donor (HLA-A, B, C, DR, and DQ loci) who is available to donate CD34+ cells. Availability of at least one 4/6 HLA-matched (HLA-A, B, and DR loci) cord blood unit from the National Marrow Donor Program (NMDP). The cord blood unit must contain a minimum TNC (prior to thawing) of at least 2x107 cells per kilogram of recipient body weight Ability to comprehend the nature of the treatment 6.2. Exclusion Criteria - Recipient (any of the following) HLA identical (6/6) related donor available and readily accessible at time of transplantation evaluation Any patient not meeting institutional standard guidelines for transplant eligibility

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a phase 1/phase 2 study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Miltenyi CliniMACS® CD34 Reagent System<br>The haploidentical donor will be mobilized by G-CSF and undergo one apheresis to collect CD34+ selected stem cell product after Miltenyi CliniMACS® CD34+ selection. The products will be cryopreserved until the time of transplantation. Recipients will receive a standard conditioning regimen. After the conditioning regimen, the subjects will receive an allograft on day 0 containing donor CD34+ cells that have been positively selected and T-cell depleted following G-CSF mobilization combined with a single UCB unit. UCB unit will not be manipulated, and will be prepared and infused separately following standard of care procedure. | Device: Miltenyi CliniMACS® CD34 Reagent System<br>* Miltenyi CliniMACS® CD34 Reagent System will be used to prepare CD34+ enriched/T-cell depleted cells from haploidentical mobilized peripheral blood.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patients with treatment-related serious adverse event rate (TRSAE) | Safety will be monitored continuously with a stopping rule for toxicity based on the treatment-related serious adverse event rate (TRSAE), defined by failure of Miltenyi CliniMACS® CD34 Reagent System to select CD34+ cells, and/or failure to engraft that is higher than historical control (<10% for hematologic malignancies and 34% for severe aplastic anemia). | 42 days | 
| The number of patients with successful engraftment | Failure defined as failure of Miltenyi CliniMACS® CD34 Reagent System to select CD34+ cells, and/or failure to engraft by day 22 for patients with hematologic malignancies, and by day 42 for patients with severe aplastic anemia. Assuming a sample size of 50, if there is an engraftment success rate of 75% (or a failure rate of 25%), there would be a resulting 95% confidence interval of 63% to 87% (that is a width of 12% on either side of 75% successful engraftments | 42 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stem Cell Transplant, Umbilical Cord Blood Transplant, Haploidentical CD34+ Selected Cells