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

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

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.

Study Overview

• Status: Terminated
• Conditions: Sickle Cell Disease; Thalassemia; Cerebral Adrenoleukodystrophy; Inherited Metabolic Disorders; High Risk Hematologic Disorders
• Intervention / Treatment: Procedure: Blood and Marrow Transplant

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Caner Center at University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophil Recovery	Incidence of neutrophil recovery by day +42	Day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Incidence of overall survival at 1 year	1 year
Primary Graft Failure (neutropenic and non-neutropenic)	Incidence of primary graft failure (neutropenic and non-neutropenic) by day +42	Day 42

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Investigators: Principal Investigator: Christen L Ebens, MD, MPH, University of Minnesota - Pediatrics Blood and Marrow Transplant

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2018
• Primary Completion (Actual): December 19, 2022
• Study Completion (Actual): December 19, 2022

Study Registration Dates

• First Submitted: December 5, 2017
• First Submitted That Met QC Criteria: December 5, 2017
• First Posted (Actual): December 8, 2017

Study Record Updates

• Last Update Posted (Actual): July 12, 2024
• Last Update Submitted That Met QC Criteria: July 9, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: SCD; cALD
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Demyelinating Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Endocrine System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Anemia; Metabolism, Inborn Errors; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Leukoencephalopathies; Adrenal Gland Diseases; Hereditary Central Nervous System Demyelinating Diseases; Peroxisomal Disorders; Adrenal Insufficiency; Hematologic Diseases; Anemia, Sickle Cell; Thalassemia; Metabolic Diseases; Adrenoleukodystrophy
• Other Study ID Numbers: 2017LS101; MT2017-30 (Other Identifier: University of Minnesota Masonic Cancer Center)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No