Immunodeficiencies
Conditions
Keywords
Blood and Marrow Transplant, T cell Depletion, Unrelated, Related, Donor
Brief summary
This is a pilot study with 2 strata to evaluate engraftment and graft vs. host disease (GVHD) in patients receiving unrelated or partially matched related donor peripheral stem cells using the CliniMACS system to positively deplete T cells to prevent severe GVHD. Feasibility will be tested, focusing on engraftment, treatment-related mortality (with a specific focus on interstitial pneumonitis) and severe GVHD.
Detailed description
PRIMARY HYPOTHESIS: T cell depletion utilizing the CliniMACS device will allow more precise, specific and controlled graft engineering of peripheral blood stem cells from unrelated and partially matched related donors without an increase in relapse or graft rejection and grade III or IV acute graft vs. host disease (GVHD). SECONDARY HYPOTHESIS: Use of the CliniMACS device will allow defined levels of T cell depletion to reflect the risk of severe GVHD in the donor/recipient pair. Thus, patients with a relatively lower risk of severe GVHD will be assigned to Stratum 1 and receive a graft with lesser T cell depletion and a defined level of reinfused T cells. Patients with higher risk of severe GVHD or for whom there is no perceived clinical benefit of GVHD will be assigned to Stratum 2 and receive a more T cell-depleted graft. Conditioning of the patient (except immunodeficiencies) includes : * Thiotepa 5 mg/kg days for 2 days * Cyclophosphamide 60 mg/kg days for 2 days * Total body irradiation 200 cGy given twice a day for 3 days Following conditioning patient's will receive stem cells that have been processed using the CliniMACS device. This processing is done in the stem cell laboratory at The Children's Hospital of Philadelphia. The Stem Cell Lab is accredited by the Foundation for the Accreditation of Cellular Therapy (FACT) and maintain complete standard operating procedures (SOP's) and procedure records. Processing of cells using the CliniMACS will occur in accordance with the Investigator Brochure and Technical Manual following the laboratory SOPs and using aseptic technique. The CHOP Stem Cell Lab has extensive prior experience with automated cell processing technologies, including the CellPro Ceprate device and the Isolex 300i.
Interventions
DEVICECliniMACs
T and B Cell depletion
Sponsors
Children's Hospital of Philadelphia
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 22 Years
Healthy volunteers
No
Inclusion criteria
As of October 2014 this study closed enrollment to malignant diseases. This study remains open to: Non-malignant diseases: 1. Bone marrow failure, including severe aplastic anemia 2. Immunodeficiencies
Exclusion criteria
1\. Patients who have had prior stem cell transplant (SCT) and bone marrow transplant (BMT) are excluded for study enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Successful Engraftment | 100 days Post Transplant | Successful engraftment will be whether subjects have achieved an absolute neutrophil count (ANC) \>500 and platelet count \>20 x 109/l by 100 days after transplant |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stratum 1 Stratum 1. CliniMACS CD3+/CD19+ depletion: Patients with donors with the following levels of matching:
* 6/6 or 8/8 matched (fully matched)
* 1 antigen or allele mismatched (mismatch at A or B or DRB1)
* 2 antigen or allele mismatched (mismatch ONLY at A and B but NOT at DRB1 plus either A or B). | 87 |
| Stratum 2 * Haploidentical match
* 2 antigen and/or allele mismatched where one of the mismatches includes DRB1 | 6 |
| Total | 93 |
Baseline characteristics
| Characteristic | Stratum 2 | Stratum 1 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 6 Participants | 80 Participants | 86 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 7 Participants | 7 Participants |
| Age, Continuous | 0.5 years | 12 years | 12 years |
| Region of Enrollment United States | 6 Participants | 87 Participants | 93 Participants |
| Sex: Female, Male Female | 0 Participants | 44 Participants | 44 Participants |
| Sex: Female, Male Male | 6 Participants | 43 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 87 | 2 / 6 |
| other Total, other adverse events | 0 / 87 | 0 / 6 |
| serious Total, serious adverse events | 6 / 87 | 2 / 6 |
Outcome results
Primary
Number of Participants With Successful Engraftment
Successful engraftment will be whether subjects have achieved an absolute neutrophil count (ANC) \>500 and platelet count \>20 x 109/l by 100 days after transplant
Time frame: 100 days Post Transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stratum 1 | Number of Participants With Successful Engraftment | 87 Participants |
| Stratum 2 | Number of Participants With Successful Engraftment | 5 Participants |