Phase 2
N=29
Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by a Donor Stem Cell Transplant in Treating Patients With Immunodeficiency or Other Nonmalignant Inherited Disorders
Immunodeficiency Syndrome · Non-Cancer Diagnosis
Bottom Line
View on ClinicalTrials.gov: NCT00553098 ↗Enrolled (actual)
29
Serious AEs
35.7%
Results posted
May 2017
Primary outcome: Primary: Number of Patients Who Achieve Greater Than 50% Donor T-cell Chimerism — 13 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Alemtuzumab (Biological); Allogeneic Bone Marrow Transplantation (Procedure); Allogeneic Hematopoietic Stem Cell Transplantation (Procedure); Cyclosporine (Drug); Fludarabine Phosphate (Drug); Laboratory Biomarker Analysis (Other); Mycophenolate Mofetil (Drug); Total-Body Irradiation (Radiation)
- Age
- Pediatric, Adult
- Sex
- All
- Sponsor
- Fred Hutchinson Cancer Center
- Primary completion
- Mar 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Patients Who Achieve Greater Than 50% Donor T-cell Chimerism |
13 | — |
| SECONDARY Overall Survival |
19 | — |
| SECONDARY Immune Reconstitution by 1 Year Post Transplant |
7 | — |
| SECONDARY Disease Response by 1 Year Post Transplant |
15 | — |
| SECONDARY Greater Than 50% CD33+ Donor Chimerisms at 1 Year Post Transplant |
8 | — |
| SECONDARY Greater Than 50% CD19+ Donor Chimerisms at 1 Year Post Transplant |
16 | — |
| SECONDARY Clinical Significant Infection, Requiring Treatment, Within 100 Days Post Transplant |
21 | — |
| SECONDARY Number of Patients Diagnosed With Acute GVHD |
18 | — |
| SECONDARY Number of Patients Diagnosed With Overall Grade 1 or Grade 2 Acute GVHD |
12 | — |
| SECONDARY Number of Patients Diagnosed With Overall Grade III or Grade IV Acute GVHD |
6 | — |
| SECONDARY Number of Patients Diagnosed With Chronic GVHD |
8 | — |
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 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 75 years old
Data sourced from ClinicalTrials.gov (NCT00553098). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.