for people ages 3 months and up (full criteria)
study started
estimated completion
Christopher C Dvorak, M.D.(ucsf)



This is a single-arm, open label, Phase 1 study to assess the safety and tolerability of CD34+CD90+ hematopoietic stem cell (HSC) allografts infused into patients with SCID who are conditioned for transplantation with AMG 191, an antibody that targets CD117 present on endogenous HSC. The target dose of CD34+CD90+ HSC will be >1 x 106 cells/kg and the optimal conditioning dose of AMG 191 will be determined during dose escalation.

Official Title

A Phase 1 Study to Evaluate the Safety and Tolerability of Tandemly-purified Allogenic CD34+CD90+ HSC Administered Following Conditioning With AMG 191 to Achieve Engraftment and Immune Reconstitution in Patients With SCID


Hematopoietic stem cell transplantation (HCT) is the only proven cure for severe combined immunodeficiency (SCID), a rare disorder in which patients do not have functional lymphocytes. Unless treated, patients with SCID generally die from infections before age two. The success of HCT depends on the type of donor, and it is often not feasible to find a fully human leukocyte antigen (HLA)-matched unrelated donor due to the need to transplant early in life before infections develop. As a result, family members who are partially HLA-matched (haploidentical) often donate their blood stem cells for the transplant. There are three primary risks associated with poor HCT outcomes for SCID patients: 1) chemotherapeutic drugs are sometimes given to prepare the patient before HCT to improve the chance of successful engraftment; but these treatments (called "conditioning") can have deleterious short and long-term side effects to which SCID patients are especially vulnerable; 2) risk for developing graft-versus-host disease (GVHD) due to reaction by donor T cells contained in allografts against recipient tissues can cause serious, life-threatening complications, especially if the donor is only partially HLA-matched; and 3) if no conditioning is used true stem cells may not engraft, which prevents development of a long-term functioning immune system, especially B lymphocytes. As consequence many such patients need life-long gammaglobulin replacement therapy.

This study will investigate a combined, two-step approach that is expected to improve the outcome of HCT for SCID: It is a phase 1 study. Hence, the study will test the safety of this two step approach.

The first part of the study will test an experimental conditioning treatment that is expected to be less toxic to patients than standard chemotherapy. This treatment involves giving a one time intravenous dose of protein, called a monoclonal antibody, which binds to a specific molecule on the surface of cells, called c-kit or CD117. The antibody that will be used is called AMG 191. AMG 191 is expected to result in depletion of recipient bone marrow stem cells and thereby improve donor blood stem cell engraftment in the recipient's bone marrow and the development of an immune system from the donor. Patients followed for clearance of antibody from blood by pharmacokinetic (PK) studies.

The second part will test if SCID patients who are conditioned for transplant with AMG 191 will do better if they have more T-cells removed from the donor grafts. T-cells normally act to attack foreign pathogens such as viruses. However, when transplanted into a recipient as part of a blood stem cell graft, T-cells can cause harm by mistakenly attacking normal tissues, including the lymphoid organs of the recipient, resulting in GVHD or a more subtle form of GVHD called subclinical GVHD which is deleterious to immune function. While removal of T-cells from blood stem cell grafts is not novel, grafts in this study will under more stringent T-cell removal because patients with SCID are particularly prone to develop GVHD. Grafts will first undergo standard selection of CD34+ cells to reduce donor T-cells and enrich for blood stem cells. A second enrichment step will purify the blood stem cells away from remaining T-cells by staining the CD34-selected cells with another CD34 binding antibody plus an antibody that binds to CD90. CD34+CD90+ cells, represent a more purified stem cell fraction, and will be isolated using a cell sorter. This part of the study will determine if GVHD can be reduced and equivalent or improved immune function achieved compared to standard grafts.


SCID Immunodeficiency Pediatric Bone Marrow Transplantation GVHD Stem Cells Chimerism Transplant BMT Severe Combined Immunodeficiency Antibodies Immunoglobulins Antibodies, Monoclonal Humanized anti-CD117 Monoclonal Antibody Blood Forming Stem Cell Transplant (CD34+CD90+) Blood Stem Cell Transplant w/ anti-CD117 conditioning


For people ages 3 months and up

Key Inclusion Criteria:

All patient groups must have:

  1. Primary Immune Deficiency as defined by specific criteria, including but not limited to the following subtypes:
  2. T-, B+, NK-: IL-2Rcγ deficient, JAK3-deficient
  3. T-, B-, NK+: RAG1/2 deficient, Artemis-deficient
  4. T-, B+, NK+: IL7Rα deficient, CD3 subunit deficient, CD45 deficient
  5. Acceptable organ function as defined in study protocol
  6. Life expectancy of at least 8 weeks
  7. Female patients of childbearing potential willing to use an effective contraceptive method for the duration of study participation

Key Inclusion Criteria for patients >/= two years of age who have had a prior allogeneic bone marrow transplant (BMT):

  1. Prior donor of appropriate age (≥ 5 years old) available for re-collection of stem cells by apheresis
  2. Previous allogeneic BMT (> 2 years prior) with poor graft function defined as one of the following:
  3. Inadequate B cell engraftment,
  4. Incomplete T cell reconstitution,
  5. Severe clinical symptoms explained by poor immunity

Key Inclusion criteria specific for patients with newly diagnosed SCID:

  1. Haploidentical donor of appropriate age (> 5 years old) or HLA-matched unrelated donor available for apheresis

Exclusion Criteria:

  1. Patients with any acute or uncontrolled infections
  2. Patients receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy
  3. Patients with active malignancies
  4. Pregnant women
  5. Women who are nursing and do not wish to discontinue breast feeding
  6. Lansky/Karnofsky performance score < 50%
  7. Patients with certain defined SCID subtypes, including:
  8. Omenn syndrome
  9. Leaky SCID
  10. Reticular dysgenesis
  11. Adenosine deaminase deficiency
  12. Purine nucleoside phosphorylase deficiency
  13. For patients who have had a prior HCT, any evidence of donor myeloid chimerism in peripheral blood by STR analysis.
  14. For patients with newly diagnosed SCID, an HLA-matched sibling eligible to donate hematopoietic cells
  15. . Active GVHD within 6 months prior to enrollment, or on immunosuppressive therapy for GVHD.


  • UCSF Benioff's Children's Hospital not yet accepting patients
    San Francisco California 94158 United States
  • Lucile Packard Children's Hospital accepting new patients
    Palo Alto California 94304 United States

Lead Scientist

  • Christopher C Dvorak, M.D. (ucsf)
    My Research Interests are divided into 3 areas of focus: 1. Supportive Care (especially Invasive Fungal Infections) following Hematopoietic Stem Cell Transplantation 2. Transplantation for Severe Combined Immunodeficiency 3.


accepting new patients
Start Date
Completion Date
Stanford University
Phase 1
Study Type
Last Updated