Bone Marrow Transplant for Dyskeratosis Congenita

Recruiting at 17 trial locations

Overseen By Suneet Agarwal, MD, PHD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Boston Children's Hospital

Must not be taking: Fludarabine, Alemtuzumab, Mycophenolate, others

Disqualifiers: MDS, AML, HIV, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new bone marrow transplant method for patients with Dyskeratosis congenita. It uses fludarabine and antibodies to avoid harmful side effects, aiming to improve survival and reduce complications. Fludarabine-based regimens have been shown to be effective and feasible in reducing transplant-related morbidity in patients with Dyskeratosis congenita.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

How does this treatment for dyskeratosis congenita differ from other treatments?

This treatment for dyskeratosis congenita is unique because it uses a combination of drugs like Alemtuzumab, Cyclosporins, Fludarabine, Mycophenolate Mofetil, and Tacrolimus, which are typically used in reduced intensity conditioning regimens. These regimens are designed to be less harsh on the body compared to traditional treatments, potentially reducing the risk of severe side effects and improving outcomes for patients with this condition. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment for Bone Marrow Transplant for Dyskeratosis Congenita?

Research on similar treatments, like the use of alemtuzumab and fludarabine in bone marrow transplants for juvenile idiopathic arthritis, shows promising results. Patients experienced significant improvement in their condition and quality of life, suggesting potential effectiveness for similar conditions. ^{6 7 8 9 10}

Research Team

Suneet Agarwal, MD, PHD

Principal Investigator

Boston Children's Hospital

Eligibility Criteria

This trial is for patients with Dyskeratosis Congenita, specifically those who have moderate or severe aplastic anemia but not Fanconi anemia. Participants need a matching bone marrow donor and good kidney function. It's not for those with prior transplants, significant allergies to the drugs used, HIV, uncontrolled infections, pregnant or breastfeeding women, certain bone marrow abnormalities, or very poor health status.

Inclusion Criteria

My bone marrow is less active than usual for my age.

I have been tested and do not have Fanconi anemia.

My kidney function is good, with a filtration rate of at least 30 ml/min.

Exclusion Criteria

You have a specific type of antibody that reacts against the donor's tissue, and it could cause health problems.

I have had a bone marrow or stem cell transplant from another person.

My bone marrow test shows changes linked to MDS or AML.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants receive alemtuzumab/fludarabine conditioning regimen

2-3 weeks

Transplantation

Participants undergo hematopoietic cell transplantation (HCT)

1 week

Follow-up

Participants are monitored for safety, immune reconstitution, and secondary malignancies

Up to 15 years

Treatment Details

Interventions

• Alemtuzumab
• Cyclosporins
• Fludarabine
• Mycophenolate Mofetil
• Tacrolimus

Trial Overview The study tests a new Bone Marrow Transplantation (BMT) regimen without radiation and alkylators in Dyskeratosis Congenita patients. The aim is to see if this less damaging approach can still successfully treat the blood system issues without worsening lung or liver disease or increasing cancer risk.

Participant Groups

Group I: alemtuzumab/fludarabine conditioning Experimental Treatment 5 Interventions

alemtuzumab/fludarabine conditioning; calcineurin-inhibitor/mycophenolate mofetil GVHD prophylaxis

Alemtuzumab is already approved in United States, European Union for the following indications:

Approved in United States as Campath for:

• Chronic lymphocytic leukemia
• Multiple sclerosis

Approved in European Union as Lemtrada for:

• Multiple sclerosis

Approved in European Union as Campath for:

• Chronic lymphocytic leukemia

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

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

Collaborator

Trials

1

Recruited

40+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Karolinska University Hospital

Collaborator

Trials

509

Recruited

1,319,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

University of Chicago

Collaborator

Trials

1,086

Recruited

844,000+

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Collaborator

Trials

10

Recruited

2,100+

Children's Hospital Los Angeles

Collaborator

Trials

257

Recruited

5,075,000+

Children's Mercy Hospital Kansas City

Collaborator

Trials

261

Recruited

941,000+

University of Wisconsin, Madison

Collaborator

Trials

1,249

Recruited

3,255,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic stem cell transplantation for severe, refractory juvenile idiopathic arthritis. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Case report: NUDT15 polymorphism and severe azathioprine-induced myelosuppression in a young Chinese female with systematic lupus erythematosus: a case analysis and literature review. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Severe thiopurine-induced leukocytopenia and hair loss in Japanese patients with defective NUDT15 variant: Retrospective case-control study. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Therapeutic strategies evaluated by the European Society of Cutaneous Lupus Erythematosus (EUSCLE) Core Set Questionnaire in more than 1000 patients with cutaneous lupus erythematosus. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Implementation of NUDT15 Genotyping to Prevent Azathioprine-Induced Leukopenia for Patients With Autoimmune Disorders in Chinese Population. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Correction of bone marrow failure in dyskeratosis congenita by bone marrow transplantation. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Allogeneic stem cell transplantation in a patient with dyskeratosis congenita after conditioning with low-dose cyclophosphamide and anti-thymocyte globulin. [2013]

8. Turkey pubmed.ncbi.nlm.nih.gov

Successful Second Unrelated Donor Hematopoietic Stem Cell Transplant in a Patient With Dyskeratosis Congenital After First Graft Rejection. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Nonmyeloablative allogeneic hematopoietic stem cell transplantation for treatment of Dyskeratosis congenita. [2016]

10. England pubmed.ncbi.nlm.nih.gov

Reduced intensity conditioning is effective for hematopoietic SCT in dyskeratosis congenita-related BM failure. [2013]