CHP 834 Unrelated and Partially Matched Related Donor Peripheral Stem Cell Transportation for T and B Cell Depletion (CliniMACs)

Children's Hospital of Philadelphia (CHOP)

Status and phase: Completed; Phase 2

Conditions: Immunodeficiencies

Treatments: Device: CliniMACs

Study type: Interventional

Funder types: Other

Identifiers

NCT00579124

05-004222

Details and patient eligibility

About

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.

Full 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.

Enrollment: 93 patients

Sex: All

Ages: Under 22 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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93 participants in 2 patient groups

1. CliniMACS CD3+/CD19+ depletion

Other group

Description:

* 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). Patients will receive grafts that have undergone CD3+ and CD19+ depletion. The CD3(-) fraction will be infused.

Treatment:

Device: CliniMACs

2. CliniMACS CD3+/CD19+ depletion

Other group

Description:

Stratum 2. CliniMACS CD3+/CD19+ depletion: * Haploidentical match * 2 antigen and/or allele mismatched where one of the mismatches includes DRB1 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.

Treatment:

Device: CliniMACs