Pilot and Feasibility Study of Reduced-Intensity Hematopoietic Stem Cell Transplant for MonoMAC

Summary

Background:

* Stem cells are immature blood cells that grow in the bone marrow and produce all of the cells needed for normal blood and immunity. Stem cells can be taken from one person (donor) and given to another person (recipient) through allogeneic stem cell transplantation. Donor stem cells can then replace the recipients stem cells in the bone marrow, restoring normal blood production and immunity. Most allogeneic transplants now use stem cells collected from the donors blood in a process called peripheral blood stem cell transplantation.
* Monocytopenia and mycobacterial infection (MonoMAC) is an immunodeficiency disease that is characterized by a lack of monocytes, a type of white blood cell, and an increased risk of developing mycobacteria infections that may cause tuberculosis.
* Allogeneic stem cell transplantation has been used successfully to treat many kinds of immune diseases and cancers that develop in blood or immune system cells. Researchers have been studying a particular kind of stem cell transplantation that uses lower than usual doses of chemotherapy and particular combinations of drugs to improve the results of the procedure for patients with blood-related cancers and pre-cancerous conditions.

Objectives:

* To determine the safety and efficacy of reduced-intensity hematopoietic stem cell transplants (a particular stem cell transplantation procedure) for treating MonoMAC.

Eligibility:

* Patients 18-60 years of age who have MonoMAC and who have been matched with a suitable stem cell donor.

Design:

* Donors and recipients will undergo separate procedures as part of this protocol.
* Donors:
* National Institutes of Health researchers will take the donor s medical history, perform a physical exam, take blood samples, and explain the procedure. Tests will be performed to check the donors heart, lung, kidney, and liver function.
* Donors will receive injections of a drug called filgrastim (G-CSF), which causes stem cells to travel from bone marrow into blood. The G-CSF shots will be given for 5 to 7 days before the collection procedure.
* Donors will undergo apheresis to collect white blood cells and stem cells directly from the blood, which can be done as an outpatient procedure. Researchers may consider the alternative of directly collecting bone marrow from the donor, which will require an overnight hospital stay.
* Recipients:
* Recipients will receive 3 days of pre-transplant chemotherapy and radiation therapy to prepare for the transplant. For 4 days before the transplant, recipients will receive the chemotherapy drug fludarabine, followed by a single dose of radiation therapy, and will also receive the drugs tacrolimus and sirolimus to prevent the donor cells from attacking the recipient s normal tissues.
* Recipients will then receive the transplant of donor stem cells and will continue to receive tacrolimus and sirolimus for 3 months after the transplant to prevent the donor cells from attacking the recipient s normal tissues. Recipients will be discharged from the hospital once their condition is stable.
* Recipients will visit the NCI clinic regularly for the first 5 months after the transplant, and then less often for at least 5 years. Recipients may receive additional donor immune cells (donor lymphocyte infusion) after the transplant if the study doctors believe they are needed.

Conditions

• MDS
• Immunodeficiency
• GATA2

Interventions

DRUG

Cyclophosphamide (CTX, Cytoxan)

14.5 mg/kg intravenous (IV) (in the vein) infusion over 30 minutes once daily on days -6 and -5 (weight based dosing) or 50 mg/kg IV infusion over 2 hours on day -6 (weight based dosing) or 50/kg IV once daily x 2 doses on days +3 and +4

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

PROCEDURE

Total Body Irradiation (TBI)

200 centigray (cGy) on Day -1 or 300 cGy on Day -1 (for 9/10 URD and Haplo patients)

PROCEDURE

Allogeneic Hematopoietic Stem Cell (HSC)

stem cell transplant

DRUG

Equine Anti-Thymocyte Globulin

30mg/kg IV (in the vein) once daily x 3 days on Days -6, -5, -4 (3 doses total)

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Dennis D Hickstein, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

12 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-05-07

Primary Completion

2014-06-12

Completion

2017-02-26

FDA Drug

Yes

Countries

• United States

Study Locations