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

Primary Purpose

Bone Marrow Failure Syndromes, Immunodeficiencies, Immune Dysregulation Syndromes

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CliniMACs device
Sponsored by
Children's Hospital of Philadelphia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bone Marrow Failure Syndromes focused on measuring Transplant related mortality, Graft versus host disease, Bone marrow transplant

Eligibility Criteria

undefined - 22 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The Children's Hospital of Philadelphia

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Bone Marrow Failure Syndrome

Immunodeficiency / Dysregulation

Arm 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.

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.

Outcomes

Primary Outcome Measures

Number of Participants With Engraftment
The primary objective is to determine event free survival with durable stable engraftment of donor cells at one year.

Secondary Outcome Measures

Full Information

First Posted
October 22, 2014
Last Updated
March 16, 2018
Sponsor
Children's Hospital of Philadelphia
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1. Study Identification

Unique Protocol Identification Number
NCT02277639
Brief Title
Reduced Intensity Conditioning Using CD3+/CD19+ Depletion for Non Malignant Transplantable Diseases
Acronym
MiniClini
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
November 2011 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Children's Hospital of Philadelphia

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bone Marrow Failure Syndromes, Immunodeficiencies, Immune Dysregulation Syndromes
Keywords
Transplant related mortality, Graft versus host disease, Bone marrow transplant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
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)
Allocation
Non-Randomized
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bone Marrow Failure Syndrome
Arm Type
Experimental
Arm 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.
Arm Title
Immunodeficiency / Dysregulation
Arm Type
Experimental
Arm 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.
Intervention Type
Device
Intervention Name(s)
CliniMACs device
Intervention Description
Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.
Primary Outcome Measure Information:
Title
Number of Participants With Engraftment
Description
The primary objective is to determine event free survival with durable stable engraftment of donor cells at one year.
Time Frame
One Year

10. Eligibility

Sex
All
Maximum Age & Unit of Time
22 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nancy Bunin, MD
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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