Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation (HaploHCT) Following Reduced Intensity Conditioning (RIC) for Selected High Risk Non-Malignant Diseases

Sponsor

Masonic Cancer Center, University of Minnesota (Other)

Overall Status

Recruiting

CT.gov ID

NCT03367546

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase II study for the use of T-cell replete reduced intensity conditioning (RIC) haploidentical donor allogeneic hematopoietic cell transplantation (HaploHCT) for individuals with high-risk non-malignant diseases who lack a suitable HLA-matched sibling donor.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease Thalassemia High Risk Hematologic Disorders Cerebral Adrenoleukodystrophy Inherited Metabolic Disorders	Procedure: Blood and Marrow Transplant	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Haploidentical Donor T-cell Replete Allogeneic Hematopoietic Cell Transplant Following Reducing Intensity Conditioning for Patients With Selected High Risk Non-Malignant Disease

Actual Study Start Date :

Jul 2, 2018

Anticipated Primary Completion Date :

Nov 1, 2025

Anticipated Study Completion Date :

Nov 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: rATG, FLU/CY/TBI, & Thiotepa Anti-Thymocyte Globulin - Rabbit (rATG), Fludarabine (Fludara), Cyclophosphamide (Cytoxan, Neosar), Total Body Irradiation (TBI), & Thiotepa	Procedure: Blood and Marrow Transplant Reduced intensity conditioning (RIC) with rabbit ATG, fludarabine, cyclophosphamide, thiotepa and low dose (2 Gy) total body irradiation followed by T-cell replete, unmanipulated, haploidentical related donor stem cell transplant (HaploHCT) and post-transplant cyclophosphamide (PTCy)

Arm

Intervention/Treatment

Experimental: rATG, FLU/CY/TBI, & Thiotepa

Anti-Thymocyte Globulin - Rabbit (rATG), Fludarabine (Fludara), Cyclophosphamide (Cytoxan, Neosar), Total Body Irradiation (TBI), & Thiotepa

Procedure: Blood and Marrow Transplant

Reduced intensity conditioning (RIC) with rabbit ATG, fludarabine, cyclophosphamide, thiotepa and low dose (2 Gy) total body irradiation followed by T-cell replete, unmanipulated, haploidentical related donor stem cell transplant (HaploHCT) and post-transplant cyclophosphamide (PTCy)

Outcome Measures

Primary Outcome Measures

Neutrophil Recovery [Day 42]
Incidence of neutrophil recovery by day +42

Secondary Outcome Measures

Overall Survival (OS) [1 year]
Incidence of overall survival at 1 year
Primary Graft Failure (neutropenic and non-neutropenic) [Day 42]
Incidence of primary graft failure (neutropenic and non-neutropenic) by day +42

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Years to 25 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Sickle Cell Disease (SCD)

If diagnosis of SCD must meet one or more of the following disease characteristics:

Stroke, CNS hemorrhage or a neurologic event lasting longer than 24 hours, or abnormal cerebral MRI or cerebral arteriogram or MRI angiographic study and impaired neuropsychological testing
Acute chest syndrome with a history of recurrent hospitalizations or exchange transfusions
Recurrent vaso-occlusive pain 3 or more episodes per year for 3 years or more years or recurrent priapism,
Impaired neuropsychological function and abnormal cerebral MRI scan
Stage I or II sickle lung disease,
Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration rate [GFR] 30-50% of the predicted normal value)
Bilateral proliferative retinopathy and major visual impairment in at least one eye
Osteonecrosis of multiple joints with documented destructive changes
Requirement for chronic transfusions
RBC alloimmunization
Transfusion Dependent Alpha- or Beta-Thalassemia
Other Non-Malignant Hematologic Disorders:

Transfusion dependent or involve other potential life-threatening cytopenias, including but not limited to Paroxysmal Nocturnal Hemoglobinuria, Glanzmann's Thrombasthenia, Severe Congenital Neutropenia and Shwachman-Diamond Syndrome

cALD
Diagnosis of ALD by abnormal plasma very long chain fatty acid (VLCFA) profile or ABCD1 gene mutation
Cerebral disease on MRI
Absence of a Major Functional Disability (cortical blindness, loss of communication, wheelchair dependence) on the ALD Neurologic Function Scale
Other inherited metabolic disorders:

Any other inherited metabolic disorder for which alloHCT is indicated and for whom, in the opinion of the treating physician, the patient's best treatment option is with a haploidentical donor following non-myeloablatve conditioning.

Age, Performance Status, Consent
Age: 0-55 years
Performance Status: Karnofsky ≥ 70%, Lansky play score ≥ 70
Consent: voluntary written consent (adult or parental/guardian)
Adequate Organ Function
Renal: Creatinine <2.0 mg/dl for adults or glomerular filtration rate > 50 ml/min for children
Hepatic: Bilirubin and ALT <3 times the upper limit of institutional normal
Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 40%.