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Immunodeficiency SyndromePhase 2NCT00553098

Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by a Donor Stem Cell Transplant in Treating Patients With Immunodeficiency or Other Nonmalignant Inherited Disorders

A Phase 2 study testing Alemtuzumab, Allogeneic Bone Marrow Transplantation and Allogeneic Hematopoietic Stem Cell Transplantation in people with Immunodeficiency Syndrome and Non-Cancer Diagnosis, run by Fred Hutchinson Cancer Center at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages Up to 54 years
What is being tested?
Alemtuzumab, Allogeneic Bone Marrow Transplantation and Allogeneic Hematopoietic Stem Cell Transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
6 sitesUnited States
Study dates
Jun 2006to Mar 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 54 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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)

Who cannot join

  • 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)
Show all 15Show fewer
  • 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

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53201

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Children's Hospital and Research Center at Oakland

    Oakland, California, 94609-1809

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

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®

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.

Read the detailed description

PRIMARY OBJECTIVES:

  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).

SECONDARY OBJECTIVES:

  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%.

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.

Being tested
Alemtuzumab, Allogeneic Bone Marrow Transplantation, Allogeneic Hematopoietic Stem Cell Transplantation, Cyclosporine, Fludarabine Phosphate
Medical subject headings
Immunologic Deficiency Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlemtuzumabBiological

    Also called Anti-CD52 Monoclonal Antibody, Campath, Campath-1H, LDP-03

    Given IV

  • Allogeneic Bone Marrow TransplantationProcedure or surgery

    Also called Allo BMT, Allogeneic BMT

    Undergo HCT

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called allogeneic stem cell transplantation, HSC, HSCT

    Undergo HCT

  • CyclosporineDrug

    Also called 27-400, Ciclosporin, CsA, Cyclosporin

    Given PO or IV

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative study

  • Mycophenolate MofetilDrug

    Also called Cellcept, MMF

    Given PO or IV

  • Total-Body IrradiationRadiation

    Also called TOTAL BODY IRRADIATION, Whole-Body Irradiation

    Undergo low dose TBI

Study groups in NCT00553098
Study groupRoleWhat they receive
Treatment (chemotherapy, low dose radiation)ExperimentalCONDITIONING 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.
Receives: Biological: Alemtuzumab; Procedure: Allogeneic Bone Marrow Transplantation; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclosporine; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Radiation: Total-Body Irradiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients Who Achieve Greater Than 50% Donor T-cell Chimerism

    The study will be considered a success and the protocol worthy of further study if there is sufficient evidence that this rate is greater than the 50% rate observed in the most recently transplanted patients with nonmalignant disorders. Analyses will be carried out separately for the alemtuzumab recipients and the TBI recipients. We will be 80% confidence of success if a one-sided 80% confidence interval for the proportion of patients with successful chimerism exceeds 50%. Cumulative incidence will be used to evaluate the probability of chimerism.

    Measured: At 1 year post transplant

Secondary outcomes (10)

  1. Overall Survival

    Number of patients alive at 1 year

    Measured: 1 year

  2. Immune Reconstitution by 1 Year Post Transplant

    Number of patients with normal range CD3 at 1 year post transplant

    Measured: 1 year

  3. Disease Response by 1 Year Post Transplant

    Number of patients at 1 year with disease response (defined as no clinical evidence of active disease and/or sufficient level of donor chimerisms to prevent disease recurrence)

    Measured: 1 year

  4. Greater Than 50% CD33+ Donor Chimerisms at 1 Year Post Transplant

    Number of patients who achieve greater than 50% CD33+ donor chimerisms at 1 year post transplant.

    Measured: 1 year

  5. Greater Than 50% CD19+ Donor Chimerisms at 1 Year Post Transplant

    Number of Patients Who Achieve Greater Than 50% CD19+ Donor Chimerisms at 1 Year Post Transplant

    Measured: 1 year

  6. Clinical Significant Infection, Requiring Treatment, Within 100 Days Post Transplant

    Number of patients who experienced a clinical significant infection, requiring treatment, within 100 days post transplant.

    Measured: 100 days

  7. Number of Patients Diagnosed With Acute GVHD

    Number of patients diagnosed with acute GVHD by Day 100 post transplant

    Measured: Day 100

  8. Number of Patients Diagnosed With Overall Grade 1 or Grade 2 Acute GVHD

    Number of patients diagnosed with overall grade I or grade II acute GVHD by Day 100 post transplant

    Measured: Day 100

  9. Number of Patients Diagnosed With Overall Grade III or Grade IV Acute GVHD

    Number of patients diagnosed with overall Grade III or Grade IV Acute GVHD by Day 100 post transplant

    Measured: Day 100

  10. Number of Patients Diagnosed With Chronic GVHD

    Number of patients diagnosed with chronic GVHD within 1 year post transplant

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2007 (estimated)
  2. Study startJun 2006
  3. Primary completionMar 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00553098
Sponsor's protocol ID
2007.00
Other IDs
NCI-2009-01550, 2007, 2007.00, P30CA015704
Status last verified
Feb 2020
First submitted
2 Nov 2007
Last updated
17 Feb 2020
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alemtuzumab, Allogeneic Bone Marrow Transplantation and Allogeneic Hematopoietic Stem Cell Transplantation in people with Immunodeficiency Syndrome and Non-Cancer Diagnosis, run by Fred Hutchinson Cancer Center at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients Who Achieve Greater Than 50% Donor T-cell Chimerism (time frame: At 1 year post transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00553098.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2020.

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