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

Immunodeficiencies Clinical Trial

Official title:

Phase II Study for Patients With Primary Immunodeficiencies Using and Cd19+ Depleted Unrelated Donor or Partially Matched Related Donor Peripheral Stem Cells

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02990819
• Other study ID #: 15-011733
• Secondary ID: 15BT022
• Status: Recruiting
• Phase: Phase 2
• Start date: December 2016
• Est. completion date: December 2025

Study information

• Verified date: May 2024
• Source: Children's Hospital of Philadelphia
• Contact: Patricia Hankins, BSN, RN, CCRC
• Phone: 215-590-5168
• Email: hankinsp[@]chop.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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. The study will include patients 0-25 years with PID, including immune dysregulation syndromes for which hematopoietic stem cell transplant is indicated. Treatment: Either conditioning regimen (listed below) followed by alpha/beta T and CD19+ depleted donor peripheral stem cells 1. Reduced intensity conditioning with busulfan x 8 doses, fludarabine 40 mg/m2 x 4, thiotepa 5 mg/kg x 2, anti-thymocyte globulin (ATG) 3 mg/kg x 3. OR 2. Myeloablative regimen with busulfan x 16 doses or Daily for four days, fludarabine 30 mg/m2 x 5, thiotepa 5 mg/kg x 2, ATG 3 mg/kg x 2. OR 3. Immunotherapy regimen on days -9, 8, 7 with anti-thymocyte globulin 3 mg/kg/day (for severe combined immunodeficiency patients only). 4. Infusion of alpha/beta T and CD19+ depleted donor peripheral stem cells. 5. Follow up, including evaluation of chimerism and immune reconstitution.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 25 Years

Eligibility

Inclusion Criteria:

1. Ages 0-25 years at time of enrollment

2. 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.

3. Clinical status

• Lansky or Karnofsky performance >=60
• Organ Function:

1. Serum creatinine <1.5 x upper limit of normal for age Hepatic: ALT <=250; AST <=350

2. Cardiac shortening fraction >=27%

3. Bilirubin <2.5x normal (unless elevation due to Gilberts disease).

4. No active untreated infection

4. Signed informed consent

5. No HLA matched related donor available.

6. Females of childbearing potential must have negative pregnancy test.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Immune Dysregulation Syndromes
• Immunodeficiencies
• Immunologic Deficiency Syndromes
• Primary Immunodeficiency Diseases

Intervention

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

Locations

Country	Name	City	State
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital of Philadelphia

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Severity of graft vs. host disease (GVHD)	Severity of acute and chronic graft vs host disease (GVHD), incidence of mixed chimerism, primary and secondary graft rejection, and immune reconstitution at one and two years	One and two years
Secondary	Incidence of graft vs. host disease (GVHD)	Evaluation of incidence of chronic graft vs host disease (GVHD), incidence of mixed chimerism, primary and secondary graft rejection, and immune reconstitution at one and two years	One and two years