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

• ClinicalTrials.gov Identifier: NCT03367546
• Recruitment Status: Recruiting
• First Posted: December 8, 2017
• Last Update Posted: May 25, 2022
• Sponsor: Masonic Cancer Center, University of Minnesota
• Information provided by (Responsible Party): Masonic Cancer Center, University of Minnesota

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 (Clinical Trial)
• Estimated 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: July 2, 2018
• Estimated Primary Completion Date: November 2025
• Estimated Study Completion Date: November 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)

Outcome Measures

Primary Outcome Measures :

1. Neutrophil Recovery [ Time Frame: Day 42 ]
   Incidence of neutrophil recovery by day +42

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: up to 25 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Lisa Burke, RN; 612-273-8482; lburke3@Fairview.org

Locations

United States, Minnesota

Masonic Caner Center at University of Minnesota; Recruiting

Minneapolis, Minnesota, United States, 55455

Contact: Lisa Burke 612-273-8482 lburke3@Fairview.org

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

• Principal Investigator: Christen L Ebens, MD, MPH; University of Minnesota - Pediatrics Blood and Marrow Transplant

More Information

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT03367546
• Other Study ID Numbers: 2017LS101; MT2017-30 ( Other Identifier: University of Minnesota Masonic Cancer Center )
• First Posted: December 8, 2017
• Last Update Posted: May 25, 2022
• Last Verified: May 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Masonic Cancer Center, University of Minnesota:

SCD; cALD

Additional relevant MeSH terms:

Adrenoleukodystrophy; Anemia, Sickle Cell; Thalassemia; Hematologic Diseases; Metabolic Diseases; Disease; Pathologic Processes; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Genetic Diseases, Inborn; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Demyelinating Diseases; Mental Retardation, X-Linked; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Peroxisomal Disorders; Adrenal Insufficiency; Adrenal Gland Diseases