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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02277639
Recruitment Status : Completed
First Posted : October 29, 2014
Results First Posted : April 11, 2018
Last Update Posted : April 11, 2018
Sponsor:
Information provided by (Responsible Party):
Nancy Bunin, Children's Hospital of Philadelphia

Tracking Information
First Submitted Date  ICMJE October 22, 2014
First Posted Date  ICMJE October 29, 2014
Results First Submitted Date  ICMJE June 26, 2017
Results First Posted Date  ICMJE April 11, 2018
Last Update Posted Date April 11, 2018
Study Start Date  ICMJE November 2011
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 16, 2018)		 Number of Participants With Engraftment [ Time Frame: One Year ]
The primary objective is to determine event free survival with durable stable engraftment of donor cells at one year.
Original Primary Outcome Measures  ICMJE
 (submitted: October 27, 2014)		 Engraftment [ Time Frame: One Year ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Reduced Intensity Conditioning Using CD3+/CD19+ Depletion for Non Malignant Transplantable Diseases
Official Title  ICMJE 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 age.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Bone Marrow Failure Syndromes
  • Immunodeficiencies
  • Immune Dysregulation Syndromes
Intervention  ICMJE Device: CliniMACs device
Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.
Study Arms  ICMJE
  • Experimental: Bone Marrow Failure Syndrome
    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.
    Intervention: Device: CliniMACs device
  • Experimental: Immunodeficiency / Dysregulation
    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.
    Intervention: Device: CliniMACs device
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 20, 2016)		 2
Original Estimated Enrollment  ICMJE
 (submitted: October 27, 2014)		 40
Actual Study Completion Date  ICMJE March 2016
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 22 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02277639
Other Study ID Numbers  ICMJE 11-008330
CHP 980 ( Other Identifier: Children's Hospital of Philadelphia )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Nancy Bunin, Children's Hospital of Philadelphia
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Children's Hospital of Philadelphia
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Nancy Bunin, MD Children's Hospital of Philadelphia
PRS Account Children's Hospital of Philadelphia
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP