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

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Brief Title

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

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 0-22 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, 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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Event free survival

Secondary Outcome

 Severity of graft vs. host disease (GVHD)

Condition

Immunodeficiencies

Intervention

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

Study Arms / Comparison Groups

 Reduced intensity regimen
Description:  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, Fludarbine, Thiotepa followed by stem cell infusion.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Device

Estimated Enrollment

40

Start Date

December 2016

Completion Date

December 2023

Primary Completion Date

December 2023

Eligibility Criteria

        Inclusion Criteria:

          1. Ages 0-22 years at time of enrollment

          2. Diseases:

               -  Immunodeficiencies for which allogeneic hematopoietic stem cell transplant is
                  indicated, including severe combined immunodeficiencies, IPEX syndrome, X-linked
                  lymphoproliferative disease, chronic granulomatous disease, WAS, hyperIgM, and
                  other life-threatening immunodeficiencies.

               -  Immune dysregulation syndromes, including refractory or recurrent hemophagocytic
                  lymphohistiocytosis, HLH with genetic mutations, refractory multisystemic
                  Langerhans cell histiocytosis, other 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.

          -  CHOP 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
      

Gender

All

Ages

N/A - 22 Years

Accepts Healthy Volunteers

No

Contacts

Nancy Bunin, MD, , [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02990819

Organization ID

15-011733

Secondary IDs

15BT022

Responsible Party

Principal Investigator

Study Sponsor

Children's Hospital of Philadelphia

Collaborators

 University of California, San Francisco

Study Sponsor

Nancy Bunin, MD, Principal Investigator, Children's Hospital of Philadelphia


Verification Date

July 2020