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

University of Minnesota (UMN)

Status and phase: Terminated; Phase 2

Conditions: High Risk Hematologic Disorders; Thalassemia; Cerebral Adrenoleukodystrophy; Inherited Metabolic Disorders; Sickle Cell Disease

Treatments: Procedure: Blood and Marrow Transplant

Study type: Interventional

Funder types: Other

Identifiers

NCT03367546

2017LS101

MT2017-30 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 5 patients

Sex: All

Ages: Under 25 years old

Volunteers: No 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%.

Exclusion criteria

• Availability of a suitable HLA-matched related donor
• Uncontrolled infection
• Pregnant or breastfeeding
• HIV positive

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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5 participants in 1 patient group

rATG, FLU/CY/TBI, & Thiotepa

Experimental group

Description:

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

Treatment:

Procedure: Blood and Marrow Transplant