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CD34+ Stem Cell Infusion to Augment Graft Function

Primary Purpose

Waning Donor Chimerism, Waning Immune Function, Primary Immunodeficiency Disease(s)

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CD34+
Sponsored by
Children's Hospital Medical Center, Cincinnati
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Waning Donor Chimerism focused on measuring Primary Immunodeficiency Disease(s), Mixed Donor Chimerism, bone marrow failure syndromes, allogeneic hematopoietic stem cell transplant (HSCT), children

Eligibility Criteria

undefined - 35 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

To be eligible for this protocol, patients must have the following:

  1. Primary immunodeficiency (e.g. SCID, Wiskott-Aldrich and/or other more rare conditions and other bone marrow failure syndromes) with prior allogeneic stem cell transplant.
  2. Waning donor chimerism or immune function that is inadequate to correct their disease or clinical condition, for which primary transplant was given, as determined by their attending physician.
  3. Available primary donor.
  4. Must not have other organ dysfunction deemed by the attending physician to preclude this procedure.
  5. Age < 35 years at time of transplant
  6. One of the following must be true:

    • Patients must have evidence of persistent or recurrent immunodeficiency or thrombocytopenia.

-OR-

• Primary immunodeficiency disease with known potential to progress to malignant condition if untreated.

-OR-

• Debilitating secondary disease known to be a consequence of inadequate immune response to known agent or pathogen, uncontrollable by other available medical therapies (e.g. third patient described on page 5).

Exclusion Criteria:

  1. Absence of an available original donor
  2. Failure to sign consent form, or inability to undergo informed consent process
  3. Pregnant or lactating female
  4. Uncontrolled GVHD

Sites / Locations

  • Cincinnati Children's Hospital Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CD34+ selected stem cell infusion

Arm Description

An infusion of selected CD34+ stem cells will be given without any preparative regimen.

Outcomes

Primary Outcome Measures

Number of Participants Who Showed Successful Augmentation of Graft Function
Successful augmentation of graft function achieved if donor chimerism is doubled compared to the value immediately pre-infusion at 12 months.

Secondary Outcome Measures

Full Information

First Posted
May 15, 2013
Last Updated
November 7, 2019
Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Hoxworth Blood Center
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1. Study Identification

Unique Protocol Identification Number
NCT01856582
Brief Title
CD34+ Stem Cell Infusion to Augment Graft Function
Official Title
Post Transplant CD34+ Selected Stem Cell Infusion to Augment Graft Function in Children With Primary Immunodeficiency Diseases and Bone Marrow Failure Syndromes
Study Type
Interventional

2. Study Status

Record Verification Date
December 2018
Overall Recruitment Status
Terminated
Why Stopped
CliniMACS CD34 Reagent System was FDA approved for clinical use; therefore, patients were treated clinically.
Study Start Date
October 2010 (undefined)
Primary Completion Date
August 15, 2018 (Actual)
Study Completion Date
August 15, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Hoxworth Blood Center

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine if infusing additional special donor cells will help to improve graft or immune function in previously transplanted children with immune deficiencies and bone marrow failures.
Detailed Description
The purpose of this study is to investigate the usefulness of infusing purified CD34+ cells of donor origin in order to augment graft function in response to declining chimerism after initially performing an allogeneic hematopoietic stem cell transplant (HSCT) for children with primary immunodeficiency diseases. This protocol will be utilized for patients with waning mixed donor chimerism that is inadequate for correction of clinical condition or disease for which stem cell transplant was performed, or for augmentation of immune function. An infusion of selected CD34+ stem cells will be given without any preparative regimen. As the children eligible for this protocol have reduced immune function and pre-existing donor chimerism, we hypothesize that stem cells will be able to engraft and the infusion will augment graft function. This therapy serves as an alternative to a second stem cell transplant that is known to be associated with significant morbidity and mortality. CD34+ stem cells will be collected from the donor used for initial stem cell transplant. Cells will be T-cell depleted (TCD) by performing a CD34 selection using the CliniMACS device (Miltenyi Biotec) in order to prevent development of new or exacerbation of existing graft versus host disease (GVHD), as avoidance of GVHD in nonmalignant diseases is desirable. There is sufficient data showing that mixed donor chimerism is adequate for reverting disease phenotype in certain primary immunodeficiencies. Observations from Europe and CCHMC show that donor chimerism might be boosted by CD34+ stem cell infusion alone without any specific preparative regimen. This therapy is likely to be associated with low toxicity due to the absence of a preparative regimen and lack of exposure to fresh donor cells capable of initiating GVHD, and offers potential significant benefit.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Waning Donor Chimerism, Waning Immune Function, Primary Immunodeficiency Disease(s), Bone Marrow Failure
Keywords
Primary Immunodeficiency Disease(s), Mixed Donor Chimerism, bone marrow failure syndromes, allogeneic hematopoietic stem cell transplant (HSCT), children

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CD34+ selected stem cell infusion
Arm Type
Experimental
Arm Description
An infusion of selected CD34+ stem cells will be given without any preparative regimen.
Intervention Type
Biological
Intervention Name(s)
CD34+
Intervention Description
CD34+ cells are selected using the CliniMACS System; without preparative regimen
Primary Outcome Measure Information:
Title
Number of Participants Who Showed Successful Augmentation of Graft Function
Description
Successful augmentation of graft function achieved if donor chimerism is doubled compared to the value immediately pre-infusion at 12 months.
Time Frame
12 months

10. Eligibility

Sex
All
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: To be eligible for this protocol, patients must have the following: Primary immunodeficiency (e.g. SCID, Wiskott-Aldrich and/or other more rare conditions and other bone marrow failure syndromes) with prior allogeneic stem cell transplant. Waning donor chimerism or immune function that is inadequate to correct their disease or clinical condition, for which primary transplant was given, as determined by their attending physician. Available primary donor. Must not have other organ dysfunction deemed by the attending physician to preclude this procedure. Age < 35 years at time of transplant One of the following must be true: Patients must have evidence of persistent or recurrent immunodeficiency or thrombocytopenia. -OR- • Primary immunodeficiency disease with known potential to progress to malignant condition if untreated. -OR- • Debilitating secondary disease known to be a consequence of inadequate immune response to known agent or pathogen, uncontrollable by other available medical therapies (e.g. third patient described on page 5). Exclusion Criteria: Absence of an available original donor Failure to sign consent form, or inability to undergo informed consent process Pregnant or lactating female Uncontrolled GVHD
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rebecca Marsh, MD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29555312
Citation
Chandra S, Bleesing JJ, Jordan MB, Grimley MS, Khandelwal P, Davies SM, Edwards S, Leemhuis T, Marsh RA. Post-Transplant CD34+ Selected Stem Cell "Boost" for Mixed Chimerism after Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation in Children and Young Adults with Primary Immune Deficiencies. Biol Blood Marrow Transplant. 2018 Jul;24(7):1527-1529. doi: 10.1016/j.bbmt.2018.03.013. Epub 2018 Mar 16.
Results Reference
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CD34+ Stem Cell Infusion to Augment Graft Function

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