Expanded Access Protocol Using CD3+/CD19+ Depleted PBSC

Early Phase 1

Recruiting

• Conditions: Leukemia; Inborn Errors of Metabolism; Immunodeficiencies; Immunodysregulation Polyendocrinopathy Enteropathy X-linked Syndrome; Bone Marrow Failure Syndromes
• Interventions: Device: Transplant of stem cells with CD3+/CD19+ depletion (CliniMACs)

• Registration Number: NCT02356653
• Lead Sponsor: Children's Hospital of Philadelphia

Brief Summary

The goal of this protocol is to expand access for patients who lack a fully HLA (Human leukocyte antigen) matched sibling donor and who are candidates for allogeneic hematopoietic stem cell transplant (HSCT). These patients have a serious or immediately life-threatening disease for which HSCT is indicated. These patients are not eligible for other Children's Hospital of Philadelphia IRB approved protocols that utilize CliniMACs technology for T depletion.

Detailed Description

Only 25-30% of patients who may benefit from HSCT have a matched related donor. There is a higher rate of complications using cells from an unrelated or partially matched related donor. T cells within the donor cells may cause a complication called graft vs. host disease (GVHD). The goal of this study is to use the CliniMACs device to remove the T cells that cause GVHD, called T cell depletion.

Study Timeline

• Study Start: 2013-12
• Study First Submitted: 2014-10-22
• Study First Submitted QC: 2015-02-04
• Study First Posted: 2015-02-05
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-03
• Last Update Posted: 2025-02-05
• Primary Completion: 2027-01
• Study Completion: 2030-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Patients who lack a fully HLA matched sibling and who are candidates for allogeneic hematopoietic stem cell transplant (HSCT) but are not deemed suitable candidates per their treating clinical team for current open institutional protocols using ClinMACs device for CD3+/CD19+ depletion.

2. Patients with the following transplantable diseases:

   Non-malignant diseases:

   Metabolic storage diseases correctable by HSCT, Bone marrow failure syndromes, Immunodeficiencies/immune dysregulation syndromes/including HLH, Hemoglobinopathies correctable and requiring HSCT, and Other diseases treated with HSCT/Other non-malignant blood, metabolic, or immune disorders for which HSCT has been recommended

   Malignant diseases:

   Acute leukemias, Chronic leukemias, Lymphomas, Myelodyplastic syndrome

3. Signed informed consent

4. Lansky or Karnofsky performance ≥60

5. Hematologic and Organ Function per current institutional SOP.

6. Infectious Evaluation as per current institutional SOP.

7. Participants of childbearing potential must have a negative pregnancy test as per institutional SOP

8. In cases that are deemed clinical emergencies (primary or secondary graft failure, severe marrow suppression), the above status criteria will be waived.

9. Patients must have an identified living donor

   • Donor selection will comply with 21 CFR 1271
   • Unrelated donor that meets the matching criteria of the NMDP with allele matching at HLA -A, -B, -C, -DRB1, and -DQB1: Unrelated donors may be a 10/10 match, a 9/10 match, or an 8/10 match if one of the mismatches is at DQB1
   • Related donor suitable for mobilization infectious disease criteria as per SOP, including HIV, HepB, HepC PCR negative.
   • CHOP BMT procedures apply for determining donor eligibility, including donor screening and testing for relevant communicable disease agents and diseases. Our donor collection program is FACT accredited.
   • Unrelated donor identified through the National Marrow Donor Program (NMDP) and fulfills the NMDP criteria for donation. Unrelated donor willing and able to undergo mobilization of peripheral stem cells and apheresis.
   • The donors selected for this IND will either be unrelated donors identified through the National Marrow Donor Program (NMDP) or related donors. Regarding the unrelated donors; NMDP procedures for determining donor eligibility include donor screening and testing for relevant communicable disease agents and diseases

Exclusion Criteria

1. Uncontrolled bacterial, viral or fungal infections
2. Fully HLA matched sibling donor
3. Donor unable to donate peripheral stem cells
4. Pregnant participants

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Expanded access to CliniMACs device for T cell depletion	Transplant of stem cells with CD3+/CD19+ depletion (CliniMACs)	access for patients who lack a fully HLA matched sibling, and who are candidates for allogeneic hematopoietic stem cell transplant (HSCT). These patients have a serious or immediately life-open protocols that utilize CliniMACs technology for T depletion. Subjects will undergo transplant of stem cells with CD3+/CD19+ depletion.

Primary Outcome Measures

Name	Time	Method
Overall Survival	1 year

Secondary Outcome Measures

Name	Time	Method
Graft versus Host Disease	1 year
Graft Failure	100 days

Trial Locations

Locations (1)

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States