Haploidentical Hematopoietic Stem Cell Transplantation (H... | NCT04207320

NCT04207320

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Stage I	Experimental	Stage I will include eligible subjects between the ages of 10-25 years.	Device: αβ+ T-cell depletion with Miltenyi CliniMACS system
Stage II	Experimental	Stage II will include eligible subjects between the ages of 2-25 years.	Device: αβ+ T-cell depletion with Miltenyi CliniMACS system

Interventions

Name	Type	Description	Arm Group Labels	Other Names
αβ+ T-cell depletion with Miltenyi CliniMACS system	Device	Haploidentical CD34+ megadose hematopoietic stem cell transplant in which cells are purified using the Miltenyi CliniMACS system designed for αβ+ T-cell receptor selection using immunomagnetic beads.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Safety, as Measured by Incidence of Graft Failure, Grade III/IV Irreversible End Organ Toxicity, Grade III/IV aGvHD, or Death Within 100 Days Post-Hap-HSCT	Graft Function: efficacy is defined as stable donor engraftment (>5% total nucleated cell DNA) and donor erythropoiesis that corrects the SCD hematologic phenotype (<50% HbS in the peripheral blood). Organ Toxicity: grade III/IV irreversible end organ toxicity based on NCI grading Graft Versus Host disease: grade III/IV aGvHD or death within 100 days post- Hap-HSCT	100 days post-Hap-HSCT

Secondary Outcomes

Measure	Description	Time Frame
Estimate 1-year Overall and Event-free Survival After Hap-HSCT	Proportion of patients at 1 year who have not died or had graft failure	1 year post transplant
Observe the Incidence of Grades I Through IV Acute GvHD

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Hemoglobin SS, SC, S-β0 Thalassemia, or SO-Arab Sickle Cell Disease
Between the ages of 2 and 25 years (Stage 1: 10-25 years; Stage II: 2-25 years)
Lack a fully matched family donor or fully matched unrelated donor register in the National Marrow Donor Program
Partially-matched family member with hemoglobin AA (normal) or hemoglobin AS (sickle trait) phenotype
SCD with Severe Phenotype, defined by the following criteria: Neurologic manifestations of sickle disease including cerebral vascular accident (CVA), transient ischemic event (TIA) or abnormal MRI findings suggestive of silent infarct; Two or more episodes of acute chest syndrome (ACS) requiring admission for transfusional or respiratory support including supplemental oxygen within [two years] of enrollment in study despite hydroxyurea therapy. Patients who cannot tolerate hydroxyurea and who experience multiple episodes of ACS will also be eligible; History of severe vaso-occlusive (VOC) disease requiring hospitalization and intravenous narcotics on 3 or more occasions per year over the two years prior to enrollment despite hydroxyurea therapy. Patients who cannot tolerate hydroxyurea and who experience multiple episodes of VOC will also be eligible; Other severe phenotype as evidenced by end organ dysfunction related to sickle cell disease.

Exclusion Criteria:

Karnofsky or Lansky score < 60%
Acute hepatitis or evidence of moderate or severe portal fibrosis on biopsy. (Biopsy will be obtained if patient has been on chronic transfusion therapy > 6 months or has a ferritin > 1000 ng/ml) or AST or ALT >5 times the upper limit of normal
Severe renal impairment (as evidenced by creatinine clearance of <50ml/minute glomerular filtration rate (GFR) < 50% predicted normal)
Cardiac function that demonstrates shortening fraction less than 26% by cardiac echocardiogram or pulmonary hypertension.
Pregnant Female.
Lactating female.
Pulmonary function with baseline O2 saturation <85% or Diffusing Capacity for Carbon Monoxide (DLCO) on pulmonary function testing (PFT) with a DLCO <40%.

Name	Affiliation	Role
John Cunningham, MD	University of Chicago	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
The University of Chicago		Chicago	Illinois	60637	United States

Arm/Group Information

ID	Title	Description
FG000	Stage I	Stage I will include eligible subjects between the ages of 10-25 years. αβ+ T-cell depletion with Miltenyi CliniMACS system: Haploidentical CD34+ megadose hematopoietic stem cell transplant in which cells are purified using the Miltenyi CliniMACS system designed for αβ+ T-cell receptor selection using immunomagnetic beads.
FG001	Stage II	Stage II will include eligible subjects between the ages of 2-25 years. αβ+ T-cell depletion with Miltenyi CliniMACS system: Haploidentical CD34+ megadose hematopoietic stem cell transplant in which cells are purified using the Miltenyi CliniMACS system designed for αβ+ T-cell receptor selection using immunomagnetic beads.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Stage I	Stage I will include eligible subjects between the ages of 10-25 years. αβ+ T-cell depletion with Miltenyi CliniMACS system: Haploidentical CD34+ megadose hematopoietic stem cell transplant in which cells are purified using the Miltenyi CliniMACS system designed for αβ+ T-cell receptor selection using immunomagnetic beads.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Safety, as Measured by Incidence of Graft Failure, Grade III/IV Irreversible End Organ Toxicity, Grade III/IV aGvHD, or Death Within 100 Days Post-Hap-HSCT

Graft Function: efficacy is defined as stable donor engraftment (>5% total nucleated cell DNA) and donor erythropoiesis that corrects the SCD hematologic phenotype (<50% HbS in the peripheral blood).

Organ Toxicity: grade III/IV irreversible end organ toxicity based on NCI grading

Graft Versus Host disease: grade III/IV aGvHD or death within 100 days post- Hap-HSCT

No subjects underwent transplant while on study. All subjects withdrawn and study closed prior to any study procedures/outcome measures performed.

Posted

100 days post-Hap-HSCT

ID	Title	Description
OG000	Stage I	Stage I will include eligible subjects between the ages of 10-25 years. αβ+ T-cell depletion with Miltenyi CliniMACS system: Haploidentical CD34+ megadose hematopoietic stem cell transplant in which cells are purified using the Miltenyi CliniMACS system designed for αβ+ T-cell receptor selection using immunomagnetic beads.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Stage I	Stage I will include eligible subjects between the ages of 10-25 years. αβ+ T-cell depletion with Miltenyi CliniMACS system: Haploidentical CD34+ megadose hematopoietic stem cell transplant in which cells are purified using the Miltenyi CliniMACS system designed for αβ+ T-cell receptor selection using immunomagnetic beads.

ID	Term
D000745	Anemia, Hemolytic, Congenital
D000743	Anemia, Hemolytic
D000740	Anemia
D006402	Hematologic Diseases