Clinical Trial: Haploidentical Hematopoietic Stem Cell Transplantation for Children With Sickle Cell Disease and Thalassemia Using CD34+ Positive Selected Grafts

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR CHILDREN WITH SICKLE CELL DISEASE AND THALASSEMIA USING CD34+ POSITIVE SELECTED GRAFTS

Brief Summary: The study is designed as a Pilot 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.

Detailed Summary:

Research subjects will undergo reduced intensity conditioning (Hydroxyurea, ATG, Fludarabine, Thiotepa, Melphalan) followed by infusion of a peripheral blood stem cell graft collected from haploidentical family donors that are CD34+ positively selected using the CliniMACS device. Sirolimus will be used for GVHD prophylaxis and given for 9 months post-transplant and then tapered off by one year

The use of the CliniMACS device for CD34 selection will be performed at CNMC through cross-reference of the master file for CliniMACS CD34+ Reagent by Milteyni Biotech (BB-MF 8061).

CliniMACs is an electromechanical device intended to isolate certain cell subsets from mixed cell populations. When used in combination with the CliniMACs CD34 reagent, it is possible to prepare extremely pure populations of CD34+ cells with upwards of 5 logs depletion of contaminating T cells within a closed and sterile system.

We intend to use this system to select cells from HLA haploidentical related donors who have been mobilized with G-CSF prior to stem cell collection. Since previous investigations of this strategy in adult patients have not translated into enhanced long term survival, we intend to limit this protocol to patients under the age of 22 as they have more rapid immune reconstitution.


Sponsor: Catherine Bollard

Current Primary Outcome: Safety [ Time Frame: 60 days ]

The primary endpoint of this trial is safety. Transplant related adverse outcomes and non-hematological toxicity will be measured through Day +60 on this objective to include:

  • Non-hematological severe (Grade IV and V) organ specific toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0)
  • Rates of non-engraftment
  • Severe acute (Grade III-IV)
  • Veno-occlusive disease of the liver
  • Idiopathic pneumonia syndrome
  • Seizures/Posterior reversible encephalopathy syndrome (PRES)


Original Primary Outcome: Same as current

Current Secondary Outcome: Overall survival [ Time Frame: 2 years ]

Overall survival upto 2 years


Original Secondary Outcome: Same as current

Information By: Children's Research Institute

Dates:
Date Received: June 13, 2014
Date Started: January 2015
Date Completion: December 2019
Last Updated: October 19, 2016
Last Verified: October 2016