Aclarubicin for the Treatment of Retinal Vasculopathy With Cerebral Leukodystrophy
Completed · Phase 1
Conditions studied: Vasculopathy, Retinal, With Cerebral Leukodystrophy, Cerebroretinal Vasculopathy, Hereditary
In brief
The goal of the investigator is to utilize Aclarubicin to treat patients with Retinal Vasculopathy with Cerebral Leukodystrophy (RVCL), a rare and devastating genetic disease with no available specific treatment. RVCL results from a mutation in the tail end of the TREX1 (Three Prime Repair Exonuclease 1) gene, a major deoxyribonucleic acid (DNA) repair enzyme. The RVCL-specific mutations cause expression of a truncated and mislocalized protein. RVCL is an inherited disorder whose symptoms begin at middle age and initially predominantly affects the eye and brain. Because it is an 'autosomal dominant' disease, it strikes both males and females equally. A person with RVCL has a 50-50 chance of transmitting the gene to each child. The investigator's published studies demonstrated in a mouse model for RVCL and in vitro studies with patients' cells that defects were corrected by use of Aclarubicin, an anthracycline antibiotic often used to treat cancer. Thus, there is a strong rationale for conducting a clinical trial of aclarubicin in patients with RVCL. The dosage to be initially administered to RVCL patients initially will be \< 10% of that typically used in cancer therapeutics and will be given monthly on four consecutive days for six months. Patients will undergo assessments every six months to determine disease response. Patients that do not have clear objective response may be dose escalated by 1 dose level with permission of the principal investigator permitting the patient has not previously experienced any toxicities requiring dose modifications. We will evaluate the safety and clinical efficacy of Aclarubicin for the treatment of RVCL and evaluate its effects on cellular function. This work will generate the first clinical research data on the investigational product's utility in treating RVCL. Patients are followed for at least 2 years upon completion of Aclarubicin administration completion. We are not longer administering the drug, but are in the post-drug follow up arm of the study.
Key facts
- Study ID
- NCT02723448
- Run by
- Washington University School of Medicine
- People needed
- 4
- Starts
- 2016-12-05
- Expected to finish
- 2020-07-23
- Last updated by the study team
- 2020-11-19
Who can join
Age: 18 and older. Sex: any. Healthy volunteers: not accepted.
You may qualify if…
- A diagnosis of Retinal Vasculopathy with Cerebral Leukodystrophy (RVCL)
- At least 18 years of age at the time of study registration
- Normal hematologic function defined as: WBC (white blood cell count) > 4 x10⁹/L, ANC (absolute neutrophil count) ( >1.5 x 10⁹/L and Platelets > 100 x10⁹/L
- Females of childbearing potential (FCBP) must agree to refrain from becoming pregnant while on study drug and for 3 months after discontinuation from study drug, and must agree to use adequate contraception including hormonal contraception, (i.e. birth control pills, etc), barrier method contraception (i.e. condoms), or abstinence during that time frame.
- Able to understand and willing to sign an IRB (Institutional Review Board) approved written informed consent document (or that of legally authorized representative, if applicable)
You may not qualify if…
- Acute bacterial, fungal, or viral infection
- Known human immunodeficiency virus (HIV) or active hepatitis B or C virus infection
- Pregnant and/or breastfeeding
- Cardiovascular disease including: congestive heart failure [left ventricular ejection fraction (LVEF) < 55%] at screening; electrocardiogram (EKG) evidence of acute ischemia or medically significant conduction system abnormalities; or unstable arrhythmia or angina
- Cumulative prior anthracycline dose of 300 mg/m²
- Known hypersensitivity to one or more of the study agents
- Currently receiving or has received any investigational drugs within the 14 days prior to the first dose of study drug
- Currently receiving or has received any immunosuppressants within the 14 days prior to the first dose of study drug
Where it is running
- Washington University School of Medicine — St Louis, Missouri, United States
Full record on ClinicalTrials.gov
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