Clinical trial NCT02990819: Alpha/Beta T and CD19+ Depleted Peripheral Stem Cells for Patients With Primary Immunodeficiencies
Official title: Phase II Study for Patients With Primary Immunodeficiencies Using and Cd19+ Depleted Unrelated Donor or Partially Matched Related Donor Peripheral Stem Cells
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Immunodeficiencies
Immune Dysregulation Syndromes
Keywords: Immunodeficiencies
Immune dysregulation syndromes
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
First posted: 2016-12-13
Enrollment: 60
Sex: ALL
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: T-depleted stem cell infusion
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Event free survival
timeFrame: One year
measure: Stable engraftment
timeFrame: One year
Secondary outcomes:
measure: Severity of graft vs. host disease (GVHD)
timeFrame: One and two years
measure: Incidence of graft vs. host disease (GVHD)
timeFrame: One and two years
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Timothy Olson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: