Alpha/Beta T and CD19+ Depleted Peripheral Stem Cells for Patients With Primary Immunodeficiencies

NCT02990819 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: 15-01173315BT022
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II trial to determine the ability of a reduced intensity conditioning regimen to allow successful engraftment with alpha/beta T and CD19+ depleted peripheral stem cell grafts from unrelated or partially matched related donors. There are two conditioning regimens depending upon patient diagnosis and age.

Conditions

Immunodeficiencies; Immune Dysregulation Syndromes

Keywords

Immunodeficiencies; Immune dysregulation syndromes

Outcome Measures

Primary Outcomes (2)

• Event free survival

  Event free survival in greater than 20 percent donor cells at one year for patients with primary immunodeficiencies (PID) who receive unrelated or partially matched related donor peripheral stem cell grafts which have been alpha/beta T depleted and CD19 depleted

  One year

• Stable engraftment

  Stable engraftment in greater than 20 percent donor cells at one year for patients with primary immunodeficiencies (PID) who receive unrelated or partially matched related donor peripheral stem cell grafts which have been alpha/beta T depleted and CD19 depleted

  One year

Secondary Outcomes (2)

• Severity of graft vs. host disease (GVHD)

  One and two years

• Incidence of graft vs. host disease (GVHD)

  One and two years

Study Arms (3)

Reduced intensity regimen

OTHER

Conditioning regimen is dependent on patient diagnosis and age. Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete alpha/beta T and CD19+ peripheral stem cells. Standard of care reduced intensity conditioning will include Busulfan, Fludarabine, Thiotepa followed by stem cell infusion.

Device: Apha/beta T and CD19+ cell depletion using CliniMACS device

Myeloablative regimen

OTHER

Conditioning regimen is dependent on patient diagnosis and age. Patients with chronic granulomatous disease or Wiskott-Aldrich syndrome will receive cyclophosphamide in lieu of thiotepa to ensure engraftment. Myeloablative regimen with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete alpha/beta T and CD19+ peripheral stem cells. Standard of care myeloablative regimen will include Busulfan, Fludarabine, Thiotepa, or Cyclophosphamide followed by stem cell infusion.

Device: Apha/beta T and CD19+ cell depletion using CliniMACS device

Immunotherapy

OTHER

Conditioning regimen is dependent on patient diagnosis and age. Severe combined immunodeficiency (SCID) patients will be conditioned with immunotherapy only followed by stem cell transplant using the CliniMACs device to deplete alpha/beta T and CD19+ peripheral stem cells. Immunotherapy regimen will include anti-thymocyte globulin followed by stem cell infusion.

Device: Apha/beta T and CD19+ cell depletion using CliniMACS device

Interventions

Apha/beta T and CD19+ cell depletion using CliniMACS device DEVICE

Stem cells will be processed using the CliniMACS device for alpha/beta and CD19+ T cell depletion. Processing of cells using the CliniMACS will occur in accordance with the Investigator Brochure and Technical Manual following the laboratory standard operating procedures (SOPs) and using aseptic technique.

Immunotherapy; Myeloablative regimen; Reduced intensity regimen

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Ages 0-25 years at time of enrollment
• Diseases:
• Immunodeficiencies for which allogeneic hematopoietic stem cell transplant is indicated, including severe combined immunodeficiencies, immunodeficiency polyendocrinopathy X-linked syndrome (IPEX), X-linked lymphoproliferative disease, chronic granulomatous disease, Wiskott-Aldrich syndrome (WAS), hyperIgM, and other life-threatening immunodeficiencies.
• Immune dysregulation syndromes, including refractory or recurrent hemophagocytic lymphohistiocytosis, hemophagocytic lymphohistiocytosis (HLH) with genetic mutations, refractory multisystemic Langerhans cell histiocytosis, other macrophage activating syndrome (MAS) refractory to standard therapy.
• Clinical status
• Lansky or Karnofsky performance \>=60
• Organ Function:
• Serum creatinine \<1.5 x upper limit of normal for age Hepatic: ALT \<=250; AST \<=350
• Cardiac shortening fraction \>=27%
• Bilirubin \<2.5x normal (unless elevation due to Gilberts disease).
• No active untreated infection
• Signed informed consent
• No HLA matched related donor available.
• Females of childbearing potential must have negative pregnancy test.

You may not qualify if:

• Uncontrolled bacterial, viral or fungal infections
• HLA matched related or unrelated donor able to donate mobilized peripheral stem cells.
• Pregnant Females
• Matched related donor available for bone marrow donation
• Donors Selection Criteria:
• Donor selection will comply with 21 CFR 1271
• Unrelated donor matched or up to one antigen mismatch as per National Marrow Donor Program (NMDP).
• Haploidentical parent or sibling able to undergo mobilization for peripheral stem cell collection. Maternal donor preferred over paternal donor if both equally haploidentical.
• Children's Hospital of Philadelphia (CHOP) Blood and Marrow Transplant (BMT) procedures apply for determining donor eligibility, including donor screening and testing for relevant communicable disease agents and diseases.
• 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

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Immunologic Deficiency Syndromes

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Timothy Olson, MD, PhD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Hematopoietic Stem Cell Transplantation (HSCT) Program

Model Details: T-depleted stem cell infusion

Study Record Dates

• First Submitted: December 5, 2016
• First Posted: December 13, 2016
• Study Start: December 1, 2016
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: November 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)