Aclarubicin for the Treatment of Retinal Vasculopathy With Cerebral Leukodystrophy (RVCL)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02723448|
Recruitment Status : Completed
First Posted : March 30, 2016
Last Update Posted : November 19, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Vasculopathy, Retinal, With Cerebral Leukodystrophy Cerebroretinal Vasculopathy, Hereditary||Drug: aclarubicin||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||4 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Aclarubicin for the Treatment of Retinal Vasculopathy With Cerebral Leukodystrophy (RVCL)|
|Actual Study Start Date :||December 5, 2016|
|Actual Primary Completion Date :||July 23, 2020|
|Actual Study Completion Date :||July 23, 2020|
Single Arm Study
Aclarubicin (6 mg/m²) will be administered intravenously through a central venous access device over 1 hour for four consecutive days (Days 2-5) of each 28 day cycle to each participant [Retinal Vasculopathy with Cerebral Leukodystrophy (RVCL) patients]. There is no maximum number of cycles.
Aclarubicin (3 mg/m²) will be administered intravenously through a central venous access device over 1 hour for four consecutive days per 28 day cycle. There is no maximum number of cycles.
Other Name: aclacinomycin-A (HCl)
- Change in Lesion Pattern on Fluid-Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI) in Retinal Vasculopathy Cerebral Leukodystrophy (RVCL) patients [ Time Frame: Change from baseline at six months ]Volume increase in lesions on FLAIR MRI between baseline and six months is assessed
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02723448
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|Principal Investigator:||John P Atkinson, MD||Washington University School of Medicine|