What is the mechanism of action of this treatment?

Dyskeratosis congenita (DC) treatments often involve bone marrow transplantation (BMT) to address bone marrow failure. Traditional BMT uses DNA-damaging agents such as alkylators and radiation, which can worsen other DC-related conditions like lung and liver disease and increase cancer risk. The modified BMT regimen being studied avoids these agents, aiming to reduce these additional health risks while still achieving successful transplantation. This is crucial for DC patients as it offers a potentially safer treatment option that mitigates the risk of exacerbating non-hematologic complications.

What side effects are associated with this type of intervention?

Traditional bone marrow transplantation (BMT) treatments for Dyskeratosis Congenita often involve alkylators and radiation, which can lead to severe side effects such as exacerbation of lung and liver disease and an increased risk of secondary cancers. The modified BMT regimen being studied aims to avoid these DNA-damaging agents to reduce such risks, potentially minimizing these severe complications.

What prior FDA approvals exist?

There are no specific FDA-approved treatments for Dyskeratosis Congenita that focus on the avoidance of DNA damaging agents in bone marrow transplantation. Traditional BMT often involves the use of alkylators and radiation, which can exacerbate complications in DC patients. The trial studying a modified BMT regimen aims to avoid these agents to reduce additional risks, but this approach is still under investigation and not yet FDA-approved.

What other types of research exist?

Promising novel alternatives to modified bone marrow transplantation for Dyskeratosis Congenita patients include the use of low-dose radiation combined with rapamycin, which promotes long-term bone marrow chimerism without the need for DNA damaging agents. This approach facilitates engraftment and could be curative for nonmalignant disorders like DC. Additionally, ongoing research into gene therapy and the use of genetically modified autologous cells may offer future treatment options.

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Monoclonal Antibodies

Bone Marrow Transplant for Dyskeratosis Congenita

Phase 2

Waitlist Available

Led By Suneet Agarwal, MD, PHD

Research Sponsored by Boston Children's Hospital

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Bone marrow hypocellular for age

Diagnosis of Fanconi anemia must be excluded by specific testing

Must not have

Prior allogeneic marrow or stem cell transplantation

Clonal cytogenetic abnormalities associated with MDS or AML on bone marrow examination

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 15 years post-bmt

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include immune system reactions due to alemtuzumab; digestive problems from mycophenolate mofetil; nervous system effects from fludarabine; and kidney dysfunction from cyclosporins. Tacrolimus might cause high blood pressure and tremors.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I have been tested and do not have Fanconi anemia.

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

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I have been diagnosed with moderate or severe aplastic anemia.

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My donor will provide a bone marrow transplant.

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I have a donor match for a transplant.

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I have been diagnosed with dyskeratosis congenita.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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

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I need assistance with all my care and cannot carry out any daily activities.

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I do not have any untreated serious infections.

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I have had a solid organ transplant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 15 years post-bmt

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 15 years post-bmt

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 15 years post-bmt for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Immune reconstitution as assessed by quantitation of lymphocyte subsets

Secondary malignancies

Viral reactivation and infection

Side effects data

From 2021 Phase 3 trial • 30 Patients • NCT01877837

36%

Infection (grade 3 and above)

24%

Graft versus host disease

Renal insufficiency

SupraVentricular Tachycardia

Alerted mental status

Posterior Reversible Encephalopathy Syndrome

Gastrointestinal bleed

Respiratory failure

Hypokalemia

100%

80%

60%

40%

20%

Study treatment Arm

Patients With Sickle Cell Anemia

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: alemtuzumab/fludarabine conditioningExperimental Treatment5 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Tacrolimus

FDA approved

Mycophenolate mofetil

2014

Completed Phase 4

~3060

alemtuzumab

2004

Completed Phase 4

~2760

Fludarabine

2012

Completed Phase 4

~1860

Cyclosporins

2018

Completed Phase 4

~220

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Dyskeratosis congenita (DC) treatments often involve bone marrow transplantation (BMT) to address bone marrow failure. Traditional BMT uses DNA-damaging agents such as alkylators and radiation, which can worsen other DC-related conditions like lung and liver disease and increase cancer risk. The modified BMT regimen being studied avoids these agents, aiming to reduce these additional health risks while still achieving successful transplantation. This is crucial for DC patients as it offers a potentially safer treatment option that mitigates the risk of exacerbating non-hematologic complications.

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