Clinical Trial: Pilot Study of Reduced-Intensity Hematopoietic Stem Cell Transplant of DOCK8 Deficiency

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Related and Unrelated Donor Hematopoietic Stem Cell Transplant of DOCK8 Deficiency

Brief Summary:

Background:

-DOCK8 deficiency is a genetic disorder that affects the immune system and can lead to severe recurrent infections and possible death from infections or certain types of cancers, including blood cancers. A stem cell transplant is a life-saving treatment for this condition. In this study we are evaluating the efficacy and safety of transplant from different donor sources for DOCK8 deficiency. The donors that we are using are matched siblings, matched unrelated donors, and half-matched donors, so called haploidentical related donors, such as as mothers or fathers or half-matched siblings.

Objectives:

-To determine whether transplant of bone marrow cells from different types of donors corrects DOCK8 deficiency.

Eligibility:

  • Donors: Healthy individuals between 4 and 60 years of age who are matched with a recipient.
  • Recipient: Individuals between 5 and 40 years of age who have DOCK8 deficiency, have suffered one or more life-threatening infections, or have had certain viral related cancers of cancer and have a stem cell donor.

Design:

  • All participants will be screened with a physical examination and medical history.

  • DONORS:

    • Donors will donate bone marrow cells or blood stem cells. If donating blood stem cells, donors will receive injections of filgrastim to release stem cells into the blood. After 5 days o

      Detailed Summary:

      Background

      Mutations in the Dedicator of Cytokinesis-8 (DOCK8) gene are responsible for an immunodeficiency disease characterized by: severe cutaneous and sinopulmonary infections with bacterial organisms; extensive cutaneous viral infections with Herpes simplex, Herpes zoster, Molluscum contagiosum, and Human Papilloma Virus; a marked elevation in serum IgE levels and eosinophilia; homozygous or compound heterozygous mutations in the dedicator of cytokinesis 8 (DOCK8) gene. Patients with DOCK8 deficiency die from severe infections, squamous cell carcinomas, or hematological malignancies. Allogeneic hematopoietic stem cell transplantation (HSCT) represents a potentially life-saving treatment for immunodeficiency diseases such as DOCK8 deficiency. In this study we will evaluate the efficacy and safety of allogeneic HSCT for DOCK8 deficiency. We are particularly interested in determining whether allogeneic HSCT using different donor sources and conditioning regimens reverses the lethal disease phenotype in DOCK8 deficiency by reconstituting normal host defense. The development of lethal squamous cell carcinomas and lymphomas arising from the immunodeficiency in DOCK8 deficiency supports therapeutic intervention before overt malignancy arises.

      Objectives

      Primary:

      -To determine whether allogeneic HSCT reconstitutes T-lymphocyte and B-lymphocyte cells and myeloid cells with normal donor cells at one year post-transplant and reverses the clinical phenotype of severe recurrent infections in patients with DOCK8 deficiency.

      Eligibility

      Patients 5-40 years old with DOCK8 deficiency who have suffered one or more life-threatening infectio
      Sponsor: National Cancer Institute (NCI)

      Current Primary Outcome: To determine whether reduced-intensity allogeneic (HSCT) reconstitutes T-lymphocyte, B-lymphocyte, and NK cell populations with normal donor cells and reverses the clinical phenotype of severe recurrent in patients with DOCK8. [ Time Frame: 2 years ]

      Original Primary Outcome:

      Current Secondary Outcome:

      • To determine the safety [ Time Frame: 2 years ]
      • To determine the incidence of acute and chronic graft-versus-host disease [ Time Frame: 2 years ]
      • Immune reconstitution [ Time Frame: 2 years ]
      • Overall survival, and disease-free survival. [ Time Frame: 2 years ]


      Original Secondary Outcome:

      Information By: National Institutes of Health Clinical Center (CC)

      Dates:
      Date Received: August 4, 2010
      Date Started: July 28, 2010
      Date Completion: December 31, 2022
      Last Updated: May 12, 2017
      Last Verified: May 3, 2017