Bone Marrow Failure, Primary Immunodeficiency Disease(s), Waning Donor Chimerism, Waning Immune Function
Conditions
Keywords
Primary Immunodeficiency Disease(s), Mixed Donor Chimerism, bone marrow failure syndromes, allogeneic hematopoietic stem cell transplant (HSCT), children
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.
Interventions
BIOLOGICALCD34+
CD34+ cells are selected using the CliniMACS System; without preparative regimen
Sponsors
Hoxworth Blood Center
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 35 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Showed Successful Augmentation of Graft Function | 12 months | Successful augmentation of graft function achieved if donor chimerism is doubled compared to the value immediately pre-infusion at 12 months. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CD34+ Selected Stem Cell Infusion An infusion of selected CD34+ stem cells will be given without any preparative regimen.
CD34+: CD34+ cells are selected using the CliniMACS System; without preparative regimen | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Died prior to Boost infusion | 1 |
Baseline characteristics
| Characteristic | CD34+ Selected Stem Cell Infusion |
|---|---|
| Age, Categorical <=18 years | 16 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment United States | 23 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 23 |
| other Total, other adverse events | 2 / 23 |
| serious Total, serious adverse events | 8 / 23 |
Outcome results
Primary
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.
Time frame: 12 months
Population: Selected data from this study was combined with a clinical retrospective study for analysis and published.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CD34+ Selected Stem Cell Infusion | Number of Participants Who Showed Successful Augmentation of Graft Function | 3 Participants |