Haploidentical Hematopoietic Cell Transplantation for Children With Hematologic Malignancies and Myelodysplasia

Study Overview
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Brief Summary
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This is a Phase I/II study designed to evaluate the kinetics of hematopoietic reconstitution and the incidence of acute chronic GVHD after partially matched related donor hematopoietic cell transplantation using an αβTCR/CD19+ cell depleted graft.

Detailed Description
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Less than 30% of patients undergoing hematopoietic cell transplantation (HCT) will have an HLA-matched sibling donor. There is a high likelihood of being unable to identify a perfect HLA matched unrelated donor, and the time to procure the marrow if such a donor is available is generally >3 months. An emerging body of literature suggests that related haploidentical HCT with innovative graft engineering may provide equal, or possibly superior, outcomes to conventional unrelated donors. This protocol is designed to test the hypothesis that HCT using an αβT cell / CD19+ B cell depleted graft from partially matched related donors will result in rapid, durable hematopoietic engraftment and rapid immune reconstitution with an acceptably low risk of severe acute and chronic GVHD.

Official Title
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HAPLEUK17, Haploidentical Hematopoietic Cell Transplantation for Children With Hematologic Malignancies and Myelodysplasia

Conditions
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Myelodysplasia, Hematologic Malignancy

Intervention / Treatment
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* Device: CliniMACS® TCRαβ/CD19 Combined Depletion System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient lacks an HLA matched sibling donor. Meets criteria nonhematopoietic organ function according to NCH BMT SOP09. If subjects have received a first HCT, they must be eligible for a second HCT if their disease has recurred. High resolution HLA and KIR typing The subject cannot have an active untreated infection. Viremia by PCR analysis is not considered an active infection but may require immediate viral prophylaxis. Patients with possible fungal infections must have had at least 2 weeks of appropriate anti- fungal therapy and be asymptomatic. Negative pregnancy test for females ≥11 years of age or post- menarche. Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator. (Non-childbearing potential defined as pre-menarche, greater than one year post-menopausal or surgically sterilized). Subjects must be ≤30 years at the time of consent. Signed consent by parent/guardian and assent if appropriate for subjects < 18 years of age. Signed consent by patient/subject if ≥18 years of age. Exclusion Criteria: Patient does not have a suitable donor who is willing and able (meets donor criteria). Patient has donor-specific anti-HLA antibodies at the time of enrollment Patient reports a history of allergic reactions to murine protein Donor Eligibility: The donor must be ≥18 years of age at the time of the informed consent conference. The donor must be a related donor The donor will be evaluated according to the current NCH BMT SOP 04 and must meet all criteria. The donor must be able and willing to undergo G-CSF mobilization and stem cell apheresis. The patient does not have donor specific anti-HLA antibodies

Ages Eligible for Study
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Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: The mobilized peripheral blood cell collection (apheresis product) will be processed using a Miltenyi CliniMACS device according to the manufacturing instructions. The processing will deplete the αβTCR+ cells and CD19+ cells from the apheresis product to formulate the graft.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CliniMACS Isolation<br>The mobilized peripheral blood cell collection (apheresis product) will be processed using a Miltenyi CliniMACS device according to the manufacturing instructions. The processing will deplete the αβTCR+ cells and CD19+ cells from the apheresis product to formulate the graft. | Device: CliniMACS® TCRαβ/CD19 Combined Depletion System<br>* The mobilized peripheral blood cell collection (apheresis product) will be processed using a Miltenyi CliniMACS device according to the manufacturing instructions. The processing will deplete the αβTCR+ cells and CD19+ cells from the apheresis product to formulate the graft.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure rates of neutrophil and platelet engraftment | Patients undergoing partially matched related donor hematopoietic cell transplantation with an αβT cell / CD19+ B cell depleted graft should have an improved rate of engraftment. | 4 years | 
| Measure incidence of acute GVHD | Patients undergoing partially matched related donor hematopoietic cell transplantation with an αβT cell / CD19+ B cell depleted graft should have a lower incidence of acute and chronic GVHD. | 4 years | 
| Measure rates of immune reconstitution | Patients undergoing partially matched related donor hematopoietic cell transplantation with an αβT cell / CD19+ B cell depleted graft should have a improved rate of immune reconstitution. | 4 years | 
| Measure rates of platelet engraftment | Patients undergoing partially matched related donor hematopoietic cell transplantation with an αβT cell / CD19+ B cell depleted graft should have an improved rate of engraftment. | 4 years | 
| Measure incidence of chronic GVHD | Patients undergoing partially matched related donor hematopoietic cell transplantation with an αβT cell / CD19+ B cell depleted graft should have a lower incidence of acute GVHD. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure overall survival | Patients undergoing partially matched related donor hematopoietic cell transplantation with an αβT cell / CD19+ B cell depleted graft overall survival and relapse rate/disease free survival rates will be evaluated as compared to other treatment methodologies. | 4 years | 
| Define nonhematopoietic regimen related toxicities | Patients undergoing partially matched related donor hematopoietic cell transplantation with an αβT cell / CD19+ B cell depleted graft will be evaluated for nonhematopoietic regimen related toxicities. | 4 years | 
| Measure relapse rate | Patients undergoing partially matched related donor hematopoietic cell transplantation with an αβT cell / CD19+ B cell depleted graft overall survival | 4 years | 
| Measure disease free survival | Patients undergoing partially matched related donor hematopoietic cell transplantation with an αβT cell / CD19+ B cell depleted graft overall survival | 4 years |