Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by a Donor Stem Cell Transplant in Treating Patients With Immunodeficiency or Other Nonmalignant Inherited Disorders
Condition: Immunodeficiency Syndrome; Non-Cancer Diagnosis
MeSH terms: Immunologic Deficiency Syndromes
Intervention: Alemtuzumab; Allogeneic Bone Marrow Transplantation; Allogeneic Hematopoietic Stem Cell Transplantation; Cyclosporine; Fludarabine Phosphate; Laboratory Biomarker Analysis; Mycophenolate Mofetil; Total-Body Irradiation
Intervention description: Given IV; Undergo HCT; Undergo HCT; Given PO or IV; Given IV; Correlative study; Given PO or IV; Undergo low dose TBI
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Antineoplastic Agents, Immunological; Alemtuzumab; Fludarabine; Fludarabine phosphate; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Maximum age: 54 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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)

        Exclusion Criteria:

          -  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 A*0101 and the
             donor is A*0101, A*0201; 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 A*0101 and the donor is A*0201, and
             this type of mismatch is not allowed

          -  Donor: Donor < 6 months old, > 75 years old