Bone Marrow Transplant for Dyskeratosis Congenita

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to bone marrow transplants for individuals with dyskeratosis congenita, a condition affecting multiple body parts and often leading to blood system failure and other serious issues. Researchers aim to perform the transplant without using certain DNA-damaging agents, which might worsen lung and liver disease or increase cancer risks. The trial employs a combination of medications, including alemtuzumab (an immunosuppressive drug) and fludarabine. It may suit those diagnosed with dyskeratosis congenita, who have a related blood disorder, and can find a suitable donor match. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using alemtuzumab and fludarabine in bone marrow transplants for dyskeratosis congenita yields promising results. One study found positive short-term outcomes with this combination, suggesting its effectiveness. These drugs replace more harmful treatments like radiation, which can damage DNA.

Patients have generally tolerated this treatment well, though some complications, such as infections or other side effects, can occur due to a weakened immune system. However, these risks are considered manageable, and the benefits can be significant in treating the blood problems caused by dyskeratosis congenita. Prospective participants should consult the trial team to understand the potential risks and benefits for their situation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using alemtuzumab and fludarabine for dyskeratosis congenita because this combination offers a unique approach to preparing patients for bone marrow transplants. Unlike standard treatments, which may not adequately address the underlying immune issues, alemtuzumab works by depleting certain immune cells, reducing the risk of transplant rejection. Fludarabine, on the other hand, enhances the anti-cancer effects, which is crucial for patients with this genetic disorder. This conditioning regimen, paired with targeted GVHD prophylaxis using calcineurin inhibitors and mycophenolate mofetil, aims to improve transplant success rates and reduce complications.

What evidence suggests that this trial's treatments could be effective for dyskeratosis congenita?

Research has shown that treatment plans using fludarabine, such as the alemtuzumab/fludarabine conditioning arm in this trial, can reduce complications during bone marrow transplants for patients with dyskeratosis congenita. When combined with alemtuzumab, fludarabine prepares the body for a transplant without using DNA-damaging agents. This method can improve survival rates by preventing harm to the lungs and liver and reducing cancer risk. Studies have found these treatment plans practical and effective in supporting the transplant process for individuals with this condition. By avoiding harmful agents, this approach aims to make bone marrow transplants safer for patients with dyskeratosis congenita. ^{1 4 6 7 8}

Who Is on the Research Team?

Suneet Agarwal, MD, PHD

Principal Investigator

Boston Children's Hospital

Are You a Good Fit for This Trial?

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.

Pregnancy or breastfeeding

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. withpower.com withpower.com/trial/bone-marrow-transplant-for-dyskeratosis-congenita-d15fc

Bone Marrow Transplant for Dyskeratosis Congenita Fludarabine-based regimens have been shown to be effective and feasible in reducing transplant-related morbidity in patients with Dyskeratosis congenita. Show ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01659606

Study Details | NCT01659606 | Radiation- and Alkylator- ... 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 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02162420?cond=(DYSKERATOSIS%20CONGENITA,%20X-LINKED)%20OR%20(DKC1)&rank=2

Hematopoietic Stem Cell Transplant for Dyskeratosis ... Fludarabine-based preparative regimen followed by an allogeneic hematopoietic stem cell transplant using related or unrelated donor in persons 0-70 years of age

4. astctjournal.org astctjournal.org/article/S2666-6367(24)00530-X/fulltext

Allogeneic Hematopoietic Cell Transplant For Bone ... We report prospectively collected standard alloHCT outcomes from a single-center, single-arm, open-label clinical trial of bone marrow or ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3736557/

OUTCOMES OF ALLOGENEIC HEMATOPOIETIC CELL ... We describe outcomes after allogeneic transplantation in 34 patients with dyskeratosis congenita transplanted between 1981 and 2009.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17724438/

Late death after unrelated-BMT for dyskeratosis congenita ... Late death after unrelated-BMT for dyskeratosis congenita following conditioning with alemtuzumab, fludarabine and melphalan.

7. researchgate.net researchgate.net/publication/6116761_Late_death_after_unrelated-BMT_for_dyskeratosis_congenita_following_conditioning_with_alemtuzumab_fludarabine_and_melphalan_4

Late death after unrelated-BMT for dyskeratosis congenita ... ... In this study, we report successful shortterm outcomes, including the ability to achieve favorable results with unrelated donor sources of hematopoietic ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00086580?term=Fludarabine&rank=3

Fludarabine (Fludara®) Plus Alemtuzumab (CAMPATH®, ... A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...