Reduced Intensity Conditioning Using CD3+/CD19+ Depletion for Non Malignant Transplantable Diseases

Brief Title

Reduced Intensity Conditioning Using CD3+/CD19+ Depletion for Non Malignant Transplantable Diseases

Official Title

Phase I/II Study of Reduced Intensity Conditioning for Patients With Non-Malignant Diseases Using CD3+/CD19+ Depleted Unrelated Donor or Partially Matched Related Donor Peripheral Stem Cells

Brief Summary

      This is a Phase II trial to determine the ability of a reduced intensity conditioning regimen
      to allow successful engraftment with CD3+ /CD19+ depleted peripheral stem cell grafts from
      mismatched donors. There are two conditioning regimens depending upon patient diagnosis and

Detailed Description

      This study will allow transplantation using a reduced intensity conditioning regimen for
      children with non-malignant diseases who lack a matched related or unrelated donor. Donors
      will be unrelated or partially matched related, depending upon urgency and availability. If
      each parent is haploidentical, the mother will be preferred, as there is evidence of reduced
      transplant related mortality and superior survival with a maternal donor. The risks of severe
      graft vs host disease (GVHD) and Epstein-Barr lymphoproliferative disorder will be reduced or
      eliminated by T and B cell depletion using the Miltenyi Clinimacs device. Patients with bone
      marrow failure syndromes, who are at high risk for rejection, will undergo pre-conditioning
      immune suppression with Thymoglobulin. It is recommended that patients with
      immunedysregulation syndromes receive pre-RIC alemtuzumab as this may reduce the risk on
      non-engraftment and hyperinflammatory states.

      Post-transplant immune suppression will be used to prevent GVHD, as CD3 depletion does not
      deplete as completely as CD34+ selection. It will be rapidly weaned if no GVHD by day 100 to
      allow immune reconstitution.

Study Phase

Phase 2

Study Type


Primary Outcome

Number of Participants With Engraftment


Bone Marrow Failure Syndromes


CliniMACs device

Study Arms / Comparison Groups

 Bone Marrow Failure Syndrome
Description:  Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

November 2011

Completion Date

March 2016

Primary Completion Date

March 2016

Eligibility Criteria

        Inclusion Criteria:

          -  Bone marrow failure syndromes for which SCT is indicated, including severe aplastic
             anemia refractory to non transplant therapies congenital neutropenia, congenital
             thrombocytopenia, congenital red cell aplasia

          -  Immunodeficiencies for which allogeneic hematopoietic stem cell transplant is
             indicated, including severe combined immunodeficiencies, Wiskott-Aldrich syndrome,
             IPEX syndrome, X-linked lymphoproliferative disease

          -  Immune dysregulation syndromes, including refractory or recurrent hemophagocytic
             lymphohistiocytosis, HLH with genetic mutations, refractory multisystemic Langerhans
             cell histiocytosis, other MAS refractory to standard therapy

          -  Organ function clearance

        Exclusion Criteria:

          -  Uncontrolled bacterial, viral or fungal infections

          -  HLA matched related or unrelated donor able to donate mobilized peripheral stem cells.

          -  Fanconi's syndrome, dyskeratosis congenita or other chromosomal fragility syndromes

          -  Pregnant Females




N/A - 22 Years

Accepts Healthy Volunteers



Nancy Bunin, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs

CHP 980

Responsible Party

Principal Investigator

Study Sponsor

Children's Hospital of Philadelphia

Study Sponsor

Nancy Bunin, MD, Principal Investigator, Children's Hospital of Philadelphia

Verification Date

March 2018