for people ages up to 54 years (full criteria)
at Oakland, California and other locations
study started



This phase II trial studies fludarabine phosphate and total-body irradiation with or without alemtuzumab followed by donor stem cell transplant to see how well it works in treating patients with immunodeficiency or other nonmalignant inherited disorders. Giving chemotherapy, such as fludarabine phosphate, a monoclonal antibody such as alemtuzumab, and radiation therapy before a donor stem cell transplant helps stop the growth of abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining abnormal cells.

Official Title

Hematopoietic Cell Transplantation for Treatment of Patients With Primary Immunodeficiencies and Other Nonmalignant Inherited Disorders Using Low-Dose TBI and Fludarabine With or Without Campath®



  1. Improve donor chimerism levels in patients with inherited nonmalignant disorders undergoing hematopoietic cell transplantation (HCT) using a reduced intensity conditioning regimen either through the addition of Campath (alemtuzumab) or a slightly higher dose of total-body irradiation (TBI).


  1. Decrease the incidence and severity of acute and chronic graft-versus-host disease (GVHD) through use of marrow as the stem cell source and Campath.

II. Assess disease response following HCT.

III. Immune reconstitution following HCT.

IV. Incidence of infections.

  1. Overall survival.

VI. Percent of patients with cluster of differentiation (CD)33/CD19 donor chimerism > 50%.


CONDITIONING REGIMEN: Patients with no life-threatening viral or fungal infections within 1 month before the planned hematopoietic cell transplantation (HCT) receive alemtuzumab intravenously (IV) over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on days -4 to -2. They also undergo low-dose TBI on day 0. Patients with hemophagocytic lymphohistiocytosis (HLH), immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1 month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo 2 low doses of TBI on day 0.


IMMUNOSUPPRESSION: Patients receive cyclosporine IV or orally (PO) 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. They also receive mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40 followed by a taper until day 96.

After completion of HCT, patients are followed up at day 84, at 6, 12, 18 and 24 months post-transplantation, and then once a year for 3 years.


Immunodeficiency Syndrome Non-Cancer Diagnosis Immunologic Deficiency Syndromes Vidarabine Cyclosporine Mycophenolic Acid Antineoplastic Agents, Immunological Alemtuzumab Fludarabine Fludarabine phosphate Antibodies Immunoglobulins Antibodies, Monoclonal Cyclosporins Allogeneic Bone Marrow Transplantation Allogeneic Hematopoietic Stem Cell Transplantation Laboratory Biomarker Analysis Mycophenolate Mofetil Total-Body Irradiation


You can join if…

Open to people ages up to 54 years

  • Primary immunodeficiency disorder or other nonmalignant inherited disease (except aplastic anemia and Fanconi anemia) treatable by allogeneic HCT
  • Patients with pre-existing medical conditions or other factors that renders them at high risk for regimen related toxicity or ineligible for a conventional myeloablative HCT
  • Donors: Related donor who is human leukocyte antigen (HLA) genotypically identical at least at one haplotype and may be genotypically or phenotypically identical for serological typing for HLA-A, B, -C, and at the allele level for -DRB1 and -DQB1; related donors must be a match or a single allele mismatch at HLA-A, B, and C (at highest resolution available at the time of donor selection) and matched at DRB1 and DQB1 by deoxyribonucleic acid (DNA) typing
  • Donors: Unrelated donors who are prospectively:
  • Matched for HLA-A, B, C, DRB1 and DQB1 by DNA typing at the highest resolution routinely available at the time of donor selection
  • Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing (no mismatching for DRB1 or DQB1 is allowed)

You CAN'T join if...

  • Patients with Aplastic anemia and Fanconi anemia
  • Patients with metabolic storage diseases who have severe central nervous system (CNS) involvement of disease, defined as intelligence quotient (IQ) score < 70
  • Cardiac ejection fraction < 30% or, if unable to obtain ejection fraction, shortening fraction of < 26%) on multi-gated acquisition (MUGA) scan or cardiac echo, symptomatic coronary artery disease, other cardiac failure requiring therapy; patients with a history of, or current cardiac disease should be evaluated with appropriate cardiac studies and/or cardiology consult; patients with a shortening fraction < 26% may be enrolled if approved by a cardiologist
  • Poorly controlled hypertension despite anti-hypertensive medications
  • Patients with clinical or laboratory evidence of liver disease will need to be evaluated for the cause of the liver disease, its clinical severity in terms of liver function and the degree of portal hypertension; patients will be excluded if they are found to have: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dl, or symptomatic biliary disease (Patients will be allowed on to the protocol with liver problems if gastroenterology approves the patient for HCT)
  • Patients who are positive for human immunodeficiency virus (HIV)
  • Females who are pregnant or breast-feeding
  • Fertile men or women who are unwilling to use contraceptives during HCT and up to 12 months post-treatment
  • Patients with fungal pneumonia with radiological progression after receipt of amphotericin formulation or mold-active azoles for greater than 1 month will not be eligible for this protocol (either regimen A or B)
  • Donors: Identical twin
  • Donors: Pregnancy
  • Donors: HIV positive
  • Donors: A positive anti-donor cytotoxic cross match is absolute donor exclusion
  • Donors: If a patient is homozygous at a particular loci, mismatching at that loci is not allowed due to an isolated graft rejection vector, i.e., patient A0101 and the donor is A0101, A0201; such a mismatch may increase the risk of graft rejection; if patient and donor pairs are both homozygous at a mismatched loci, they are considered a two-HLA antigen mismatch, i.e., the patient is A0101 and the donor is A*0201, and this type of mismatch is not allowed

  • Donor: Donor < 6 months old, > 75 years old


  • Children's Hospital and Research Center at Oakland
    Oakland California 94609-1809 United States
  • Oregon Health and Science University
    Portland Oregon 97239 United States


in progress, not accepting new patients
Start Date
Fred Hutchinson Cancer Research Center
Phase 2
Study Type
Last Updated