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CD34+ Stem Cell Infusion to Augment Graft Function

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ClinicalTrials.gov Identifier: NCT01856582
Recruitment Status : Terminated (CliniMACS CD34 Reagent System was FDA approved for clinical use; therefore, patients were treated clinically.)
First Posted : May 17, 2013
Last Update Posted : December 19, 2018
Sponsor:
Collaborator:
Hoxworth Blood Center
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

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.

Condition or disease Intervention/treatment Phase
Waning Donor Chimerism Waning Immune Function Primary Immunodeficiency Disease(s) Bone Marrow Failure Biological: CD34+ Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : October 2010
Actual Primary Completion Date : August 15, 2018
Actual Study Completion Date : August 15, 2018


Arm Intervention/treatment
Experimental: CD34+ selected stem cell infusion
An infusion of selected CD34+ stem cells will be given without any preparative regimen.
Biological: CD34+
CD34+ cells are selected using the CliniMACS System; without preparative regimen




Primary Outcome Measures :
  1. Augmentation of graft function [ Time Frame: 3, 6 and 12 months; annually thereafter until up to 3 years post-infusion ]

    Graft function will be measured in two ways. Firstly the percentage of donor chimerism, and secondly measured improvement in immune function; improvement in numbers of circulating white blood cells and/or platelets, and/or clearance of opportunistic viral infections.

    • Improvement in immune function studies compared to baseline levels.
    • In the case of Wiskott-Aldrich syndrome, improvement of platelet count to >20,000/L.
    • Clinical response to infection, if applicable.


Secondary Outcome Measures :
  1. Frequency and characteristics of potential infusion-related toxicity [ Time Frame: up to 12 hours post-infusion ]
    While there is little expectation of infusion-related toxicity, the incidence of infusion-related reactions will be recorded and evaluated.



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Ages Eligible for Study:   up to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01856582


Locations
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United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Hoxworth Blood Center
Investigators
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Principal Investigator: Rebecca Marsh, MD Children's Hospital Medical Center, Cincinnati

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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT01856582     History of Changes
Other Study ID Numbers: 2010-2344
First Posted: May 17, 2013    Key Record Dates
Last Update Posted: December 19, 2018
Last Verified: December 2018

Keywords provided by Children's Hospital Medical Center, Cincinnati:
Primary Immunodeficiency Disease(s)
Mixed Donor Chimerism
bone marrow failure syndromes
allogeneic hematopoietic stem cell transplant (HSCT)
children

Additional relevant MeSH terms:
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Immunologic Deficiency Syndromes
Pancytopenia
Immune System Diseases
Hematologic Diseases