Last updated on January 2019

Fludarabine Phosphate Cyclophosphamide and Total-Body Irradiation Followed by Donor Bone Marrow Transplant and Cyclophosphamide Mycophenolate Mofetil Tacrolimus and Sirolimus in Treating Patients With Primary Immunodeficiency Disorders or Noncancerous Inherited Disorders

Brief description of study

This phase I/II trial studies the side effects of fludarabine phosphate, cyclophosphamide and total-body irradiation followed by donor bone marrow transplant and cyclophosphamide, mycophenolate mofetil, tacrolimus, and sirolimus in treating patients with primary immunodeficiency disorders or noncancerous inherited disorders. Giving low doses of chemotherapy and total-body irradiation before a bone marrow transplant helps prepare the patient's body to accept the incoming donor's bone marrow and decrease the risk that the patient's immune system will reject the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells called graft versus host disease. Giving cyclophosphamide, mycophenolate mofetil, tacrolimus, and sirolimus after the transplant may help decrease this from happening.

Detailed Study Description


I. Determine safety of nonmyeloablative conditioning and hematopoietic cell transplantation (HCT) from human leukocyte antigen (HLA)-haploidentical related donors for patients with nonmalignant inherited disorders who do not have an HLA-matched related or unrelated donor.


I. Determine whether nonmyeloablative conditioning and HCT from an HLA-haploidentical related donor graft can establish mixed chimerism (> 5% cluster of differentiation [CD]3+ donor T-cell chimerism) in patients with nonmalignant inherited disorders.

II. Transplant related mortality at day 100.

III. Incidence and severity of graft-versus-host disease (GHVD).

IV. Immune reconstitution.

V. Infections during the first 200 days after HCT.


NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 1 hour on days -6 to -2; cyclophosphamide IV over 1 hour on days -6 and -5; and undergo total body irradiation on day -1.

TRANSPLANTATION: Patients undergo allogeneic bone marrow transplant on day 0.

POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on days 3 and 4, and mycophenolate mofetil orally (PO) every 8 hours on days 5-30 then twice daily (BID) to day 40, and then if there is no evidence of active GVHD and donor engraftment is > 95% (or by principal investigator [PI] approval) taper until approximately day 96, or faster at discretion of PI. Patients also receive tacrolimus IV continuously over 22-24 hours starting on day 5 post-transplant and continue on tacrolimus through day 100 followed by a taper to approximately day 180 if there is no evidence of GVHD and their graft is doing well. Patients may convert to oral tacrolimus given BID or three times daily (TID) when the patient is able to take medications orally and has a therapeutic drug level. In addition, patients will receive sirolimus orally beginning on day 5 through day 180 followed by a taper to approximately day 210 if there is no evidence of GVHD and their graft is doing well.

After completion of study treatment, patients are followed up at 6, 12, 18, and 24 months, and then annually thereafter.

Clinical Study Identifier: NCT00358657

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Recruitment Status: Open

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