About this trial
Participants are being asked to take part in this study because treatment of his or her disease requires a stem cell transplant. Stem cells or "mother" cells are the source of normal blood cells and lead to recovery of blood counts after bone marrow transplantation. Unfortunately, there is not a perfectly matched stem cell donor (like a sister or brother) for the participant and his or her disease does not permit enough time to identify another donor (like someone from a registry list that is not his or her relative) or another suitable donor has not been identified. However, a close relative of the patient has been identified whose stem cells are not a perfect match, but can be used.
Alternatively, the patient may have already received a stem cell transplant but have evidence of mixed chimerism, which means some of the patient's own bone marrow cells are present, rather than all of the donor's cells. This may lead to an increased risk of the disease coming back. Or, the patient may have all donor cells but his or her bone marrow is not working very well, which may lead to frequent blood or platelet (cells that help in clotting blood) transfusions or infection.
Regardless of the reason, it may be necessary to isolate stem cells from a haploidentical (half-match) donor in order to provide bone marrow function. Because the stem cells from the donor are only half-matched to the participant, the risk of graft-versus-host disease (GvHD) is very high. GvHD is a complication after transplant caused by donor T cells (graft) that attack the transplant recipient, and this complication can cause death after transplant. Thus, it is important that the donor's blood cells are treated to minimize cells that are most likely to attack the host's tissues. This is done by using a special device to capture the CD34+ stem cells from the donor's stem cell product prior to giving the cells to the host. This method minimizes the donor T cells, which are responsible for causing GvHD.
Purpose: In an effort to lower the occurrences and severity of graft-versus-host disease in patients and to lower the rate of transplant failure, investigators would like to specially treat the donor's blood cells to minimize the cells that are most likely to attack the patient's tissues.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patient requiring allogeneic SCT
Age between birth and 70 years
Patient and/or responsible person able to understand and sign consent
Disqualifiers
Active, acute GvHD > grade II or extensive, chronic GvHD
Severe life, threatening infection
Pulmonary dysfunction (FEV1, FVC or DLCO 40% of predicted or 3 SD below normal)
Cardiac dysfunction (LVSF less than 25%)
Trial design
Parallel
Treatments tested in this trial
CliniMACS CD34 Reagent system
DeviceA special machine that separates out the donor cells that have been mixed with a special protein, CD34 antibody, that binds to the stem cells from the white blood cells.
Treatment groups
Trial outcomes
Primary outcomes
For Cohort 1: the rate of primary engraftment 50 days post SCT
Primary engraftment is defined as achievement of absolute neutrophil count (ANC) is greater than or equal to 500/ul for three consecutive days by day 50 post transplant. The treatment regimen will be considered clinically useful if the primary engraftment rate is at least 85%.
For Cohort 2 (Without Conditioning) and Cohort 3 (With Conditioning): The total incidence of overall acute GvHD (greater than or equal to grade 3)
The overall incidence of acute GvHD will be measured 100 days post stem cell transplant. The regimen will be considered acceptable if aGvHD greater than or equal to grade 3 rate is at least 10% or lower.
Secondary outcomes
Assessment of Long Term Survival
Long term survival of recipients of G-CSF mobilized peripheral blood stem cells depleted of T cells by positive selection for the CD34+ antigen
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Baylor College of Medicine
Lead sponsor
Center for Cell and Gene Therapy, Baylor College of Medicine
Collaborator
The Methodist Hospital Research Institute
Collaborator