Clinical trial NCT03431090: Haploidentical Hematopoietic Cell Transplantation for Children With Hematologic Malignancies and Myelodysplasia
Official title: HAPLEUK17, Haploidentical Hematopoietic Cell Transplantation for Children With Hematologic Malignancies and Myelodysplasia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Myelodysplasia
Hematologic Malignancy
Lead sponsor: Nationwide Children's Hospital
Sponsor class: OTHER
First posted: 2018-02-13
Enrollment: 20
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Measure rates of neutrophil and platelet engraftment
timeFrame: 4 years
measure: Measure incidence of acute GVHD
timeFrame: 4 years
measure: Measure rates of immune reconstitution
timeFrame: 4 years
measure: Measure rates of platelet engraftment
timeFrame: 4 years
measure: Measure incidence of chronic GVHD
timeFrame: 4 years
Secondary outcomes:
measure: Measure overall survival
timeFrame: 4 years
measure: Define nonhematopoietic regimen related toxicities
timeFrame: 4 years
measure: Measure relapse rate
timeFrame: 4 years
measure: Measure disease free survival
timeFrame: 4 years
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
Study officials:
References: