Clinical trial NCT03367546: Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation (HaploHCT) Following Reduced Intensity Conditioning (RIC) for Selected High Risk Non-Malignant Diseases
Official title: Haploidentical Donor T-cell Replete Allogeneic Hematopoietic Cell Transplant Following Reducing Intensity Conditioning for Patients With Selected High Risk Non-Malignant Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Sickle Cell Disease
Thalassemia
High Risk Hematologic Disorders
Cerebral Adrenoleukodystrophy
Inherited Metabolic Disorders
Keywords: SCD
cALD
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2017-12-08
Enrollment: 5
Sex: ALL
Minimum age (years): 0
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Neutrophil Recovery
timeFrame: Day 42
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 1 year
measure: Primary Graft Failure (neutropenic and non-neutropenic)
timeFrame: Day 42
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Caner Center at University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota - Pediatrics Blood and Marrow Transplant
name: Christen L Ebens, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: