Haploidentical Hematopoietic Stem Cell Transplantation

• Status: Active, not recruiting
• Trial end date: 2023-04-01
• Target enrollment: 0
• Participant gender: All

Summary

The study is designed as a Pilot/Phase 1 trial of reduced intensity Haploidentical HSCT in patients with sickle cell disease and thalassemia. The purpose of the study is to assess the safety and toxicity of reduced intensity conditioning haploidentical hematopoietic stem cell transplantation.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Catherine Bollard
• Collaborators: Children's National Research Institute; Children's Research Institute
• Treatments: Everolimus; Sirolimus

Criteria

Inclusion Criteria:

• First allogeneic transplant

• Age up to 22 years

• Patients with severe sickle cell disease (stroke, elevated TCD velocities, >2 acute chest syndrome, ongoing chronic red cell transfusion > 6 months)

• Patients with transfusion dependent thalassemia and evidence of iron overload

• Patients must have a related donor that is HLA-matched at >/=4 of 8 but <8/8 HLA-A, -B, -C and -DRB1

• Cardiac function: Shortening fraction >25%; ejection fraction >40%

• Estimated creatinine clearance greater than 50 mL/minute

• Pulmonary function: DLCO ≥40% (adjusted for hemoglobin) and FEV1≥50% in patients 7 years and older with normal cognitive function and able to perform the test adequately. If not able to complete the testing a CT chest will be required., oxygen saturation>91%

• Liver function: direct (conjugated) bilirubin < 2x the upper limit of normal and ALT/AST < 2.5x the upper normal limit.

• Signed informed consent.

Exclusion Criteria:

• Life expectancy less than 6 months

• Patients with uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms) within 1 month prior to conditioning. Patients with febrile illness or suspected minor infection should await clinical resolution prior to starting conditioning.

• Pregnant or breastfeeding patients

• Patients seropositive for the human immunodeficiency virus (HIV)

• Patient with active Hepatitis B or C determined by serology and/or NAAT

• Active hepatitis, bridging fibrosis or cirrhosis on liver biopsy (biopsy required for patients on chronic transfusion therapy for > 1 year and evidence of iron overload with ferritin >1000 ng/mL)

• Patients with suitable 8/8 HLA matched related and unrelated donors

• Patients who have an intolerance to or have received alemtuzumab in the prior 6 months will be excluded from enrollment unless alemtuzumab is replaced with rabbit ATG in the conditioning regimen