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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.
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 :
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1. CliniMACS CD3+/CD19+ depletion | Other |
Patients will receive grafts that have undergone CD3+ and CD19+ depletion. The CD3(-) fraction will be infused. |
|
| 2. CliniMACS CD3+/CD19+ depletion | Other | Stratum 2. CliniMACS CD3+/CD19+ depletion:
For patients in Stratum 2 we will perform CD3+ (T cell) and CD19+ (B cell) depletion. There will be no T cell add back in this stratum. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CliniMACs | Device | T and B Cell depletion |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 100 days Post Transplant |
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Inclusion Criteria:
As of October 2014 this study closed enrollment to malignant diseases. This study remains open to:
Non-malignant diseases:
Exclusion Criteria:
1. Patients who have had prior stem cell transplant (SCT) and bone marrow transplant (BMT) are excluded for study enrollment.
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| Name | Affiliation | Role |
|---|---|---|
| Nancy J Bunin, MD | Children's Hospital of Philadelphia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31765697 | Result | Seif AE, Li Y, Monos DS, Heidemann SC, Aplenc R, Barrett DM, Casper JT, Freedman JL, Grupp SA, Margolis DA, Olson TS, Teachey DT, Keever-Taylor CA, Wang Y, Talano JM, Bunin NJ. Partially CD3+-Depleted Unrelated and Haploidentical Donor Peripheral Stem Cell Transplantation Has Favorable Graft-versus-Host Disease and Survival Rates in Pediatric Hematologic Malignancy. Biol Blood Marrow Transplant. 2020 Mar;26(3):493-501. doi: 10.1016/j.bbmt.2019.11.022. Epub 2019 Nov 22. |
| Label | URL |
|---|---|
| Partially CD3+ -Depleted Unrelated and Haploidentical Donor Peripheral Stem Cell Transplantation Has Favorable Graft-versus-Host Disease and Survival Rates in Pediatric Hematologic Malignancybiol | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | 1. CliniMACS CD3+/CD19+ Depletion |
Patients will receive grafts that have undergone CD3+ and CD19+ depletion. The CD3(-) fraction will be infused. CliniMACs: T and B Cell depletion |
| FG001 | 2. CliniMACS CD3+/CD19+ Depletion | Stratum 2. CliniMACS CD3+/CD19+ depletion:
For patients in Stratum 2 we will perform CD3+ (T cell) and CD19+ (B cell) depletion. There will be no T cell add back in this stratum. CliniMACs: T and B Cell depletion |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Stratum 1 | Stratum 1. CliniMACS CD3+/CD19+ depletion: Patients with donors with the following levels of matching:
|
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Posted | Count of Participants | Participants | 100 days Post Transplant |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AEs for Total Number of Participants: Stratum 1 | this group is total subject count evaluated for AE results in Stratum 1 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Non-relapsed mortality | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Patricia Hankins | Children's Hospital of Philadelphia | 215 590 5168 | hankinsp@chop.edu |
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| ID | Term |
|---|---|
| D007153 | Immunologic Deficiency Syndromes |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
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| Stratum 2 |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
|
|
| 0 |
| 87 |
| 6 |
| 87 |
| 0 |
| 87 |
| EG001 | AEs for Total Number of Participants: Stratum 2 | this group is total subject count evaluated for AE results in Stratum 2 | 2 | 6 | 2 | 6 | 0 | 6 |
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