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

Sickle Cell Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03367546
• Other study ID #: 2017LS101
• Secondary ID: MT2017-30
• Status: Terminated
• Phase: Phase 2
• Start date: July 2, 2018
• Est. completion date: December 19, 2022

Study information

• Verified date: February 2024
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: December 19, 2022
• Est. primary completion date: December 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 25 Years

Eligibility

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

Related Conditions & MeSH terms

• Adrenoleukodystrophy
• Anemia, Sickle Cell
• Cerebral Adrenoleukodystrophy
• Hematologic Diseases
• High Risk Hematologic Disorders
• Inherited Metabolic Disorders
• Metabolic Diseases
• Sickle Cell Disease
• Thalassemia

Intervention

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)

Locations

Country	Name	City	State
United States	Masonic Caner Center at University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neutrophil Recovery	Incidence of neutrophil recovery by day +42	Day 42
Secondary	Overall Survival (OS)	Incidence of overall survival at 1 year	1 year
Secondary	Primary Graft Failure (neutropenic and non-neutropenic)	Incidence of primary graft failure (neutropenic and non-neutropenic) by day +42	Day 42