Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by a Donor Stem Cell Transplant in Treating Patients With Immunodeficiency or Other Nonmalignant Inherited Disorders
NCT ID: NCT00553098
Last Updated: 2020-02-17
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
29 participants
INTERVENTIONAL
2006-06-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer
NCT00118352
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
NCT00358657
Fludarabine and Radiation Therapy in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Chronic Phase or Accelerated Phase Chronic Myelogenous Leukemia
NCT00110058
Alemtuzumab, Fludarabine Phosphate, and Low-Dose Total Body Irradiation Before Donor Stem Cell Transplantation in Treating Patients With Hematological Malignancies
NCT00040846
Myeloablative Allo HSCT With Related or Unrelated Donor for Heme Disorders
NCT03314974
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
I. 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).
SECONDARY OBJECTIVES:
I. 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.
V. Overall survival.
VI. Percent of patients with cluster of differentiation (CD)33/CD19 donor chimerism \> 50%.
OUTLINE:
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.
HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT 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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Treatment (chemotherapy, low dose radiation)
CONDITIONING REGIMEN: \*Patients with no life-threatening viral or fungal infections within 1 month before the planned HCT receive alemtuzumab 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 HLH, 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.
HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine IV or 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.
Alemtuzumab
Given IV
Allogeneic Bone Marrow Transplantation
Undergo HCT
Allogeneic Hematopoietic Stem Cell Transplantation
Undergo HCT
Cyclosporine
Given PO or IV
Fludarabine Phosphate
Given IV
Laboratory Biomarker Analysis
Correlative study
Mycophenolate Mofetil
Given PO or IV
Total-Body Irradiation
Undergo low dose TBI
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Alemtuzumab
Given IV
Allogeneic Bone Marrow Transplantation
Undergo HCT
Allogeneic Hematopoietic Stem Cell Transplantation
Undergo HCT
Cyclosporine
Given PO or IV
Fludarabine Phosphate
Given IV
Laboratory Biomarker Analysis
Correlative study
Mycophenolate Mofetil
Given PO or IV
Total-Body Irradiation
Undergo low dose TBI
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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 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
54 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
National Heart, Lung, and Blood Institute (NHLBI)
NIH
Fred Hutchinson Cancer Center
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Lauri Burroughs
Principal Investigator
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Lauri Burroughs
Role: PRINCIPAL_INVESTIGATOR
Fred Hutch/University of Washington Cancer Consortium
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Children's Hospital and Research Center at Oakland
Oakland, California, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Oregon Health and Science University
Portland, Oregon, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2009-01550
Identifier Type: REGISTRY
Identifier Source: secondary_id
2007
Identifier Type: -
Identifier Source: secondary_id
2007.00
Identifier Type: OTHER
Identifier Source: secondary_id
2007.00
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.