Dose Escalation & Expansion Study of Oral VRx-3996 & Valganciclovir in Subjects With EBV-Associated Lymphoid Malignancies

March 1, 2024 updated by: Viracta Therapeutics, Inc.

A Phase 1b/2 Open-Label, Dose Escalation & Expansion Study of Orally Administered VRx-3996 & Valganciclovir in Subjects With Epstein-Barr Virus-Associated Lymphoid Malignancies

A two part, Phase 1b/2 study to define a recommended Phase 2 dose of VRx-3996 in combination with valganciclovir (Phase 1b) designed to evaluate the efficacy of this combination in relapsed/refractory EBV+ lymphomas.

Study Overview

Detailed Description

The purpose of this study is to determine whether VRx-3996 in combination with valganciclovir is safe, determine the side effect profile, and to determine whether this therapy may help patients with EBV-related lymphomas. The study has two phases. Goals of the first phase include determining a safe and tolerable dose that can be administered in phase 2. Goals of the second phase include further evaluating the safety and tolerability of VRx-3996 in combination with valganciclovir, evaluating how the drugs are metabolized in the body, evaluating response rates and other exploratory objectives that will help the researchers evaluate how these drugs work in the body. Participants will receive daily oral doses of the two study drugs and will have multiple study visits where they will have blood collected, physical examinations, and other medical monitoring. Following completion of the Ph2, the study will enroll additional patients into a PK cohort to investigate the PK parameters of the tablet formulation.

Study Type

Interventional

Enrollment (Actual)

64

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • BA
      • Salvador, BA, Brazil, 40110-090
        • Centro de Hematologia e Oncologia da Bahia (CEHON)
    • PE
      • Recife, PE, Brazil, 50040-000
        • Hospital de Cancer de Pernambuco (HCP)
    • Rio Grande Do Sul
      • Porto Alegre, Rio Grande Do Sul, Brazil
        • Hospital do Câncer Mãe de Deus
    • SP
      • São Paulo, SP, Brazil, 08270-070
        • Hospital Santa Marcelina
      • São Paulo, SP, Brazil, 01321-001
        • Real e Benemérita Associação Portuguesa de Beneficência
      • São Paulo, SP, Brazil, 05403-000
        • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
    • California
      • Los Angeles, California, United States, 90033
        • USC Norris Comprehensive Cancer Center
      • Los Angeles, California, United States, 90404
        • University of California, Los Angeles
      • Orange, California, United States, 92868
        • UC Irvine Chao Family Comprehensive Cancer Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Anschutz Cancer Pavilion
    • Florida
      • Orange City, Florida, United States, 32763
        • Mid Florida Hematology and Oncology Center
      • Weeki Wachee, Florida, United States, 34607
        • ASCLEPES Research Centers
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute, Emory University
      • Augusta, Georgia, United States, 30912
        • Georgia Cancer Center at Augusta University
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University Feinberg School of Medicine
      • Chicago, Illinois, United States, 60612
        • Ruth M Rothstein CORE Center
    • Indiana
      • Indianapolis, Indiana, United States, 46237
        • Indiana Blood and Marrow Transplantation
    • Kansas
      • Westwood, Kansas, United States, 66205
        • The University of Kansas Cancer Center and Medical Pavilion
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
    • Montana
      • Billings, Montana, United States, 59102
        • St. Vincent Healthcare Cancer Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • John Theurer Cancer Center at Hackensack UMC
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10065
        • Weill Cornell Medical College - New York Presbyterian Hospital
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Wexner Medical Center James Cancer Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University
    • Texas
      • Dallas, Texas, United States, 75246
        • Texas Oncology - Baylor Sammons Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Relapsed/refractory, pathologically confirmed EBV+ lymphoid malignancy or lymphoproliferative disease
  • Absence of available therapy with reasonable likelihood of cure or significant clinical benefit
  • Adequate hematologic, hepatic and renal function as defined by laboratory assessment

Key Exclusion Criteria:

  • Known primary CNS lymphoma
  • Known CNS metastases or leptomeningeal disease unless appropriately treated and neurologically stable for at least 4 weeks
  • Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
  • Refractory graft versus host disease (GvHD) not responding to treatment
  • Known active hepatitis B virus infection
  • Circulating hepatitis C virus on qPCR
  • Known history of HHV-6 chromosomal integration
  • Known history of HIV infection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1b Dose Escalation

VRx-3996 (cohort 1) and valganciclovir

VRx-3996 (cohort 2) and valganciclovir

VRx-3996 (cohort 3) and valganciclovir

VRx-3996 (cohort 4) and valganciclovir

VRx-3996 (cohort 5) and valganciclovir

Taken orally once or twice daily
Other Names:
  • Nanatinostat
Taken orally once or twice daily
Experimental: Phase 2 Dose Expansion
VRx-3996 (RP2D: recommended phase 2 dose) and valganciclovir
Taken orally once or twice daily
Other Names:
  • Nanatinostat
Taken orally once or twice daily
Experimental: PK Cohort
Assessment of VRx-3996 tablet and valganciclovir PK parameters at the RP2D
Taken orally once or twice daily
Other Names:
  • Nanatinostat
Taken orally once or twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events and changes in clinical safety laboratory values in Dose Escalation and Cohort Expansion
Time Frame: Up to approximately 2 years
Determination of a safe and tolerable Recommended Phase 2 Dose (RP2D)
Up to approximately 2 years
Incidence of Dose Limiting Toxicities in Dose Escalation and Cohort Expansion
Time Frame: Up to approximately 2 years
Up to approximately 2 years
ORR as measured by stable disease (SD), partial response (PR), and complete response (CR) by radiographic assessment
Time Frame: Up to approximately 2 years
Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Single-dose and steady-state Cmax of VRx-3996 and valganciclovir
Time Frame: Through Cycle 2 Day 15 (each cycle is 28 days)
PK assessment of both VRx-3996 and valganciclovir pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1 and C2D1 and pre-dose and at hour 2 on C1D2 ,C1D15, and C2D15
Through Cycle 2 Day 15 (each cycle is 28 days)
Single-dose and steady-state AUC of VRx-3996 and valganciclovir
Time Frame: Through Cycle 2 Day 15 (each cycle is 28 days)
PK assessment of both VRx-3996 and valganciclovir pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1 and C2D1 and pre-dose and at hour 2 on C1D2 ,C1D15, and C2D15
Through Cycle 2 Day 15 (each cycle is 28 days)
Steady-state elimination half-life of VRx-3996 and valganciclovir
Time Frame: Through Cycle 2 Day 15 (each cycle is 28 days)
PK assessment of both VRx-3996 and valganciclovir pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1 and C2D1 and pre-dose and at hour 2 on C1D2, C1D15, and C2D15
Through Cycle 2 Day 15 (each cycle is 28 days)
Time to response
Time Frame: Approximately 6 months
The time from the start of first study drug administration to the first overall tumor response observed for subjects who achieved a CR or PR
Approximately 6 months
Duration of response
Time Frame: Up to approximately 2 years
The time interval (days) from date of the first overall response (CR or PR; achieved after study drug administration) to the date of disease progression
Up to approximately 2 years
Progression-free survival
Time Frame: Up to approximately 2 years
The interval between the date of first study drug administration and the date of PD or death, whichever is first reported
Up to approximately 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Jill DeFratis Robinson, Viracta Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 29, 2018

Primary Completion (Actual)

April 1, 2023

Study Completion (Actual)

May 4, 2023

Study Registration Dates

First Submitted

December 20, 2017

First Submitted That Met QC Criteria

January 10, 2018

First Posted (Actual)

January 12, 2018

Study Record Updates

Last Update Posted (Estimated)

March 5, 2024

Last Update Submitted That Met QC Criteria

March 1, 2024

Last Verified

October 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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