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

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 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 2 and 60 years of age who are matched with a recipient.
* Recipient: Individuals between 4 and 35 years of age who have confirmed DOCK8 deficiency, have suffered at least one 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 bloodwork, a physical examination and medical history.
* DONORS:

--Donors who have donate bone marrow cells or blood stem cells will have a sample of blood/bone marrow stored to be compared with the recipients sample after transplant.
* RECIPIENTS:

* Recipients receiving 10/10 matched related or unrelated donors will receive 4 days of chemotherapy with busulfan and fludarabine to suppress their immune system and prepare them for the transplant. Donors receiving 9/10 matched related or unrelated donors as well as haploidentical related donors will receive 5 days chemotherapy with cyclophosphamide, fludarabine, and busulfan. They will also receive one dose of radiation to suppress their immune system and prepare them for the transplant.
* After the initial chemotherapy and radiation (if indicated), recipients will receive the donated stem cells as a single infusion.
* After the stem cell transplant, recipients will receive two days of a chemotherapy called cyclophosphamide on day's + 3 and + 4 followed by two drugs tacrolimus and mycophenolate to prevent graft versus host disease where the donor cells attack the patient's body. All patients will remain in the hospital for at least approximately 1 month, and will be followed with regular visits for up to 3 years with periodic visits thereafter to evaluate the success of the transplant and any side effects.

Conditions

• DOCK8 Deficiency

Interventions

PROCEDURE

Reduced-intensity hematopoietic stem cell

stem cell transplant

DRUG

Fludarabine(Fludara, Berlex Laboratories)

40 mg/m2 IV (in the vein) over 30 minutes (in the vein) once daily on Days -6, -5, -4, and -3 or 30 mg/m2 IV over 30 minutes (in the vein) once daily on Days -6, -5, -4, -3, and -2

DRUG

Cyclophosphamide(CTX, Cytoxan)

14.5 mg/kg IV (in the vein) infusion over 30 min on days -6, and -5

PROCEDURE

Total Body Irradiation (TBI)

200 cGy on Day -1

DRUG

Busulfan (Busulfex)

3.2 mg/kg IV (in the vein) over 3 hours once daily on Days -6, -5, -4 and -3 (weight based dosing) or on days -4, -3 and -2

PROCEDURE

Donor peripheral blood stem cell mobiliation and collection

Donors undergo peripheral blood stem cell (PBSC) collection by apheresis will have their CD34 cells mobilized into the blood with filgrastim (Neupogen, Amgen)

PROCEDURE

Bone Marrow Harvest Procedure

Bone marrow from haploidentical related donors, and, in some cases, matched related donors will be harvested under routine conditions in the operating room. General or spinal anesthesia will be employed.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Corina E Gonzalez, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

4 Years

Max Age

120 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2010-10-05

Primary Completion

2026-10-31

Completion

2028-10-31

Countries

• United States

Study Locations