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Dyskeratosis CongenitaPhase 2NCT01659606

Radiation- and Alkylator-free Bone Marrow Transplantation Regimen for Patients With Dyskeratosis Congenita

A Phase 2 study testing alemtuzumab, Fludarabine and Cyclosporins in people with Dyskeratosis Congenita and Hoyeraal Hreidarsson Syndrome, run by Boston Children's Hospital at 13 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Dyskeratosis congenita is a disease that affects numerous parts of the body, most typically causing failure of the blood system. Lung disease, liver disease and cancer are other frequent causes of illness and death. Read more about this study

Who is it for?
Ages 30 days to 65 years
What is being tested?
alemtuzumab, Fludarabine and Cyclosporins
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
13 sitesin 3 countries
Study dates
Jul 2012to Dec 2034
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 30 days to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Bone marrow hypocellular for age
  • Moderate or severe aplastic anemia defined by one of the following: peripheral blood neutrophils < 0.5 x 10^9/L; platelets < 30 x 10^9/L or platelet transfusion dependence; reticulocytes < 50 x 10^9/L in anemic patients or red cell transfusion dependence
  • Diagnosis of dyskeratosis congenita based on clinical triad of abnormalities of skin pigmentation, nail dystrophy, oral leukoplakia; OR one of clinical triad and presence of two or more associated features; OR a pathogenic mutation in DKC1,TERC, TERT, NOP10, NHP2, TCAB1, TINF2, CTC1, PARN, RTEL1, ACD, NAF1, STN1, or ZCCHC8, as reported by a CLIA-approved laboratory; OR age-adjusted mean telomere length < 1%ile in peripheral blood lymphocytes as reported by a CLIA-approved laboratory; OR Hoyeraal-Hreidarsson syndrome; OR Revesz syndrome
  • Availability of a related or unrelated donor with a 7/8 or 8/8 match for HLA-A, B, C, and DRB1.
  • Patient and/or legal guardian must be able to sign informed consent.
  • Donor must provide a marrow allograft.
  • Diagnosis of Fanconi anemia must be excluded by mitomycin C or diepoxybutane chromosomal breakage testing on peripheral blood at a CLIA-approved laboratory (not required for patients with a genetic mutation consistent with DC)
  • Adequate renal function with glomerular filtration rate equal to or greater than 30 ml/min/1.73 m2

Who cannot join

  • Clonal cytogenetic abnormalities associated with MDS or AML on bone marrow examination.
  • Karnofsky/Lansky performance status < 40.
  • Uncontrolled bacterial, viral or fungal infections.
  • Positive test for the human immunodeficiency virus (HIV).
  • Pregnancy or breastfeeding.
  • Known severe or life-threatening allergy or intolerance to fludarabine, alemtuzumab, mycophenolate mofetil or both cyclosporine and tacrolimus.
Show all 9Show fewer
  • Positive patient anti-donor HLA antibody, which is deemed clinically significant.
  • Prior allogeneic marrow or stem cell transplantation.
  • Prior solid organ transplantation.

Trial locations and contacts

13 sites in 3 countries.

13 sites in 3 countries

United States11 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Boston Children's Hospital (pediatric patients)

    Boston, Massachusetts, 02115

  • Dana-Farber Cancer Institute (adult patients)

    Boston, Massachusetts, 02115

  • University of Chicago

    Chicago, Illinois, 60637

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Children's Mercy Hospital Kansas City

    Kansas City, Missouri, 64108

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Fred Hutch/University of Washington/Seattle Children's Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

Norway1 site

  • Oslo University Hospital

    Oslo

Other trials in Norway

Sweden1 site

  • Karolinska University Hospital

    Stockholm

Other trials in Sweden

About this study

Official title: Radiation- and Alkylator-free Hematopoietic Cell Transplantation for Bone Marrow Failure Due to Dyskeratosis Congenita / Telomere Disease

Dyskeratosis congenita is a disease that affects numerous parts of the body, most typically causing failure of the blood system. Lung disease, liver disease and cancer are other frequent causes of illness and death. Bone marrow transplantation (BMT) can cure the blood system but can make the lung and liver disease and risk of cancer worse, because of DNA damaging agents such as alkylators and radiation that are typically used in the procedure. Based on the biology of DC, we hypothesize that it may be possible to avoid these DNA damaging agents in patients with DC, and still have a successful BMT. In this protocol we will test whether a regimen that avoids DNA alkylators and radiation can permit successful BMT without compromising survival in patients with DC.

Read the detailed description

Dyskeratosis congenita (DC) is an inherited multisystem disorder, which classically presents with a clinical triad of skin pigment abnormalities, nail dystrophy, and oral leukoplakia. DC is part of a spectrum of telomere biology disorders, which include some forms of inherited idiopathic aplastic anemia, myelodysplastic syndrome, and pulmonary fibrosis and the congenital diseases Hoyeraal-Hreidarsson syndrome and Revesz syndrome. Progressive bone marrow failure (BMF) occurs in more than 80% of patients under 30 years of age and is the primary cause of morbidity and mortality, followed by pulmonary failure and malignancies. Allogeneic hematopoietic cell transplantation (HCT) is curative for the hematological defects, but several studies have demonstrated poor outcomes in DC patients due to increased early and late complications. A predisposition to pulmonary failure, vascular disease and secondary malignancies may contribute to the high incidence of fatal complications following HCT in DC patients, and provides an impetus to reduce exposure to chemotherapy and radiotherapy in preparative regimens. Recent studies suggest that fludarabine-based conditioning regimens provide stable engraftment and may avoid the toxicities seen after HCT for DC, but studies to date are limited to case reports, retrospective studies and a single prospective trial. In this study, we propose to prospectively evaluate the efficacy of a fludarabine- and antibody-based conditioning regimen in HCT for DC patients, with the goals of maintaining donor hematopoiesis and transfusion independence while decreasing early and late complications of HCT for DC.

Being tested
alemtuzumab, Fludarabine, Cyclosporins, Mycophenolate mofetil, Tacrolimus
Keywords
dyskeratosis congenita, bone marrow failure, aplastic anemia, bone marrow transplantation, reduced intensity conditioning, campath, fludarabine, telomere
Medical subject headings
Dyskeratosis Congenita, Hoyeraal Hreidarsson syndrome, Revesz Debuse syndrome, Anemia, Aplastic, Bone Marrow Failure Disorders

What participants receive

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

  • alemtuzumabBiological

    Also called Campath-1H

    Conditioning: alemtuzumab 0.2 mg/kg/dose IV/SC x 5 doses

  • FludarabineDrug

    Also called Fludara

    fludarabine 30 mg/m2/dose IV x 6 doses

  • CyclosporinsDrug

    Also called cyclosporine A, Neoral, Sandimmune

  • Mycophenolate mofetilDrug

    Also called Cellcept

  • TacrolimusDrug

    Also called FK506, Prograf

Study groups in NCT01659606
Study groupRoleWhat they receive
alemtuzumab/fludarabine conditioningExperimentalalemtuzumab/fludarabine conditioning; calcineurin-inhibitor/mycophenolate mofetil GVHD prophylaxis
Receives: Biological: alemtuzumab; Drug: Fludarabine; Drug: Cyclosporins; Drug: Mycophenolate mofetil; Drug: Tacrolimus

What is being measured

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

  1. Primary engraftment

    Measured: Up to day +100 post-BMT

Secondary outcomes (10)

  1. Survival to day+100 post-BMT

    Measured: Up to day+100 post-BMT

  2. Viral reactivation and infection

    Number of participants with DNA virus (cytomegalovirus, Epstein Barr virus, or adenovirus) reactivation/infection detected by PCR screening will be reported.

    Measured: Up to day +100 post-BMT

  3. Treatment related adverse events as assessed by CTCAE version 4.0

    Measured: Up to 1 year post-BMT

  4. Secondary graft failure

    Measured: Up to 15 years post-BMT

  5. Acute and chronic graft-versus-host disease (GVHD)

    Measured: Up to 15 years post-BMT

  6. Engraftment monitoring (chimerism)

    Measured: Up to 15 years post-BMT

  7. Immune reconstitution as assessed by quantitation of lymphocyte subsets

    Number of participants with quantitative defects in lymphocyte subset numbers following BMT

    Measured: Up to 15 years post-BMT

  8. Changes in pulmonary function as assessed by pulmonary function testing

    Measured: Up to 15 years post-BMT

  9. Secondary malignancies

    Number of patients with malignancies following BMT

    Measured: Up to 15 years post-BMT

  10. Long-term survival

    Measured: Up to 15 years post-BMT

Timeline

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

  1. First posted8 Aug 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionDec 2026 (estimated)
  4. Study completionDec 2034 (estimated)

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
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01659606
Sponsor's protocol ID
12-950
Other IDs
IRB-P00003466
Status last verified
Jan 2025
First submitted
6 Aug 2012
Last updated
27 Mar 2026
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Bhoopalan SV, Wlodarski M, Reiss U, Triplett B, Sharma A. Reduced-intensity conditioning-based hematopoietic cell transplantation for dyskeratosis congenita: Single-center experience and literature review. Pediatr Blood Cancer. 2021 Oct;68(10):e29177. doi: 10.1002/pbc.29177. Epub 2021 Jun 4.

    PubMed 34086408

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing alemtuzumab, Fludarabine and Cyclosporins in people with Dyskeratosis Congenita and Hoyeraal Hreidarsson Syndrome, run by Boston Children's Hospital at 13 sites in 3 countries.

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 8 inclusion and 9 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: under way, not looking for participants, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States, Norway, Sweden. 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?

This study is still under way. Results are not available in the source record yet.

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?

Primary engraftment (time frame: Up to day +100 post-BMT). 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 NCT01659606, which also lists 1 linked publication.

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 27 Mar 2026.

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