Mesenchymal Stromal Cells for Haplo Hematopoietic Cell Transplantation for Sickle Cell Disease

Sickle Cell Disease Clinical Trial

Official title: A Phase I Study of Mesenchymal Stromal Cells to Promote Stem Cell Engraftment in Patients With Severe Sickle Cell Disease Undergoing Haploidentical Hematopoietic Cell Transplantation

Status Withdrawn

Clinical Trial Summary

This trial is being conducted as a step toward testing the long-term hypothesis that freshly cultured, autologous mesenchymal stromal cells (MSCs) grown in platelet lysate-containing medium will modulate recipient T-cell immune responses and promote engraftment in haploidentical hematopoietic cell transplant (HCT) recipients. As a phase I, dose escalation trial of autologous MSCs in patients with sickle cell disease (SCD) undergoing haploidentical HCT, the main aim is to evaluate the safety of this therapy with a secondary aim to evaluate its effects on engraftment and graft-versus-host disease (GVHD).

Clinical Trial Description

This is a single center, phase I, open label dose escalation study designed to determine the safety and tolerability of autologous, bone marrow-derived MSCs (EPIC2016-MSC003) in patients with SCD undergoing haploidentical HCT.

Study participants are assigned to one of three MSC dose levels: four infusions of MSCs given once per week, four infusions given twice per week, or six infusions given twice per week. Bone marrow (1-2 ml/kg, max 60 ml) will be collected from study participants for autologous MSC expansion a minimum of 28 days prior to first planned MSC infusion. MSCs will be expanded ex vivo in human platelet lysate to the specified dose level. All MSC infusions will be dosed at 2 x 10^6 MSCs/kg recipient weight, with first infusion given on day 0 (day of haploidentical HCT) or day +1. This phase I trial will enroll 12-18 patients with severe SCD undergoing haploidentical HCT, with subjects followed for 1 year following HCT (and MSC infusions).

Prior to MSC infusions, study participants will undergo transplant conditioning and GVHD prophylaxis as follows:

Day -100 to -10: Hydroxyurea 30 mg/kg PO Qday

Day -9: Rabbit anti-thymocyte globulin (ATG) 0.5 mg/kg IV

Day -8: Rabbit ATG 2 mg/kg IV

Day -7: Rabbit ATG 2 mg/kg IV; Thiotepa 10 mg/kg IV

Day -6: Fludarabine 30 mg/m2 IV; Cyclophosphamide 14.5 mg/kg IV

Day -5: Fludarabine 30 mg/m2 IV; Cyclophosphamide 14.5 mg/kg IV

Day -4: Fludarabine 30 mg/m2 IV

Day -3: Fludarabine 30 mg/m2 IV

Day -2: Fludarabine 30 mg/m2 IV

Day -1: Total body irradiation (TBI) 200 centigray (cGy)

Day 0: Haploidentical bone marrow stem cell infusion

Day +3: Cyclophosphamide 50 mg/kg IV

Day +4: Cyclophosphamide 50 mg/kg IV

Day +5: Sirolimus (through day +365); mycophenolate mofetil (MMF) 15 mg/kg/dose three times per day (TID) (through day +35) ;

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

• NCT number: NCT03298399
• Study type: Interventional
• Source: Emory University
• Status: Withdrawn
• Phase: Phase 1
• Start date: December 21, 2017
• Completion date: October 25, 2018