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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
Sponsor:
Information provided by (Responsible Party):
John P. Atkinson, MD, Washington University School of Medicine

Brief Summary:

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
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.
Drug: aclarubicin
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)




Primary Outcome Measures :
  1. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. A diagnosis of Retinal Vasculopathy with Cerebral Leukodystrophy (RVCL)
  2. At least 18 years of age at the time of study registration
  3. 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
  4. 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.
  5. 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)

Exclusion Criteria:

  1. Acute bacterial, fungal, or viral infection
  2. Known human immunodeficiency virus (HIV) or active hepatitis B or C virus infection
  3. Pregnant and/or breastfeeding
  4. 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
  5. Cumulative prior anthracycline dose of 300 mg/m²
  6. Known hypersensitivity to one or more of the study agents
  7. Currently receiving or has received any investigational drugs within the 14 days prior to the first dose of study drug
  8. Currently receiving or has received any immunosuppressants within the 14 days prior to the first dose of study drug

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Information from the National Library of Medicine

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


Locations
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United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
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Principal Investigator: John P Atkinson, MD Washington University School of Medicine
Publications:

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Responsible Party: John P. Atkinson, MD, Professor of Medicine, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02723448    
Other Study ID Numbers: ATK2016001
First Posted: March 30, 2016    Key Record Dates
Last Update Posted: November 19, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data will be shared among the principal investigator and the sub-investigators.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: The data is currently being shared among the principal investigator and the subinvestigators
Access Criteria: IPD is available on REDCap or as provided by principal investigator
Additional relevant MeSH terms:
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Vascular Diseases
Cardiovascular Diseases
Aclarubicin
Aclacinomycins
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs