NCT03128996

Reduced Intensity Conditioning and Familial HLA-Mismatched BMT for Non-Malignant Disorders

A Phase I/II Trial of Reduced Intensity Conditioning and Familial HLA-Mismatched Bone Marrow Transplantation in Children With Non-Malignant Disorders

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 29 (estimated)
• Sponsor: Washington University School of Medicine · Academic / Other
• Sex: All
• Age: 1 Day – 21 Years
• Healthy volunteers: Not accepted

Summary

This study is designed to estimate the efficacy and toxicity of familial HLA mismatched bone marrow transplants in patients with non-malignant disease who are less than 21 years of age and could benefit from the procedure.

Detailed description

Patients \< 21 years of age with a non-malignant disorder benefited by hematopoietic stem cell transplant will receive a reduced intensity conditioning regimen consisting of hydroxyurea, alemtuzumab, fludarabine, thiotepa, and melphalan. This will be followed by a familial HLA-mismatched bone marrow transplant. The primary objective is to establish safety and donor cell engraftment at 100 days and 1 year post-transplant.

Conditions

• Severe Sickle Cell Disease
• Bone Marrow Failure Syndromes
• Metabolic Disorders
• Immunologic Disorders
• Hemoglobinopathies
• Non-malignant Disorders

Interventions

Type	Name	Description
DRUG	RIC regimen	Days -60 to -21: hydroxyurea (30mg/kg/day po) \>6hrs prior to 1st dose: alemtuzumab (3mg IV) Day -21: alemtuzumab (10mg IV or S/C) Day -20: alemtuzumab (15mg IV or S/C) (10mg if \< 10kg) Day -19: alemtuzumab (20mg IV or S/C) (10mg if \< 10kg) Days -8 to -4: fludarabine (30mg/m2/day IV) Day -4: thiotepa (8mg/kg IV) Day -3: melphalan (140mg/m2) Days -2 to -1: rest days/no therapy Day 0: bone marrow transplant
DRUG	GVHD prophylaxis regimen	Day +3 to +4: cyclophosphamide (50mg/kg/day IV) Day +5: Start of tacrolimus \& Start of mycophenolate mofetil (MMF) Days +5, +14, +30, +60, +90: abatacept (IND) (10mg/kg/day IV) Day +90: rituximab (375mg/m2 IV once) Patients \>/= 12 yrs - Days +120 to +180: abatacept (IND) monthly (10mg/kg/day IV) Patients \>/= 12 yrs - Days +210 to +390: abatacept (IND) monthly (5mg/kg/day) Patients \<12 yrs - Days +120 to +390: abatacept (IND) monthly (5mg/kg/day IV)

Timeline

• Start date: 2017-03-20
• Primary completion: 2028-04-01
• Completion: 2033-04-01
• First posted: 2017-04-26
• Last updated: 2026-01-07

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study