Cerebral Adrenoleukodystrophy, High Risk Hematologic Disorders, Inherited Metabolic Disorders, Sickle Cell Disease, Thalassemia
Conditions
Keywords
SCD, cALD
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.
Interventions
PROCEDUREBlood 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)
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 25 Years
Healthy volunteers
No
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%.
Exclusion criteria
* Availability of a suitable HLA-matched related donor * Uncontrolled infection * Pregnant or breastfeeding * HIV positive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neutrophil Recovery | Day 42 | Incidence of neutrophil recovery by day +42 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed