Clinical trial NCT00579124: CHP 834 Unrelated and Partially Matched Related Donor Peripheral Stem Cell Transportation for T and B Cell Depletion
Official title: CHP 834 Unrelated and Partially Matched Related Donor Peripheral Stem Cell Transportation With the CliniMACs Device for T and B Cell Depletion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Immunodeficiencies
Keywords: Blood and Marrow Transplant
T cell Depletion
Unrelated
Related
Donor
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
First posted: 2007-12-21
Enrollment: 93
Sex: ALL
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Successful Engraftment
timeFrame: 100 days Post Transplant
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Nancy J Bunin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.