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

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ClinicalTrials.gov Identifier: NCT03397706
Recruitment Status : Recruiting
First Posted : January 12, 2018
Last Update Posted : July 10, 2020
Sponsor:
Information provided by (Responsible Party):
Viracta Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE December 20, 2017
First Posted Date  ICMJE January 12, 2018
Last Update Posted Date July 10, 2020
Actual Study Start Date  ICMJE March 29, 2018
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 19, 2020)
  • Incidence of adverse events and changes in clinical safety laboratory values in Dose Escalation and Cohort Expansion [ Time Frame: Approximately 2 years ]
    Determination of a safe and tolerable Recommended Phase 2 Dose (RP2D)
  • Incidence of Dose Limiting Toxicities in Dose Escalation and Cohort Expansion [ Time Frame: Approximately 2 years ]
    Determine safety and tolerability
  • ORR as measured by stable disease (SD), partial response (PR), and complete response (CR) by radiographic assessment [ Time Frame: Approximately 2 years ]
    Disease response will be assessed using a combination of physical exam and imaging
Original Primary Outcome Measures  ICMJE
 (submitted: January 10, 2018)
  • Incidence of adverse events and changes in clinical safety laboratory values in Dose Escalation and Cohort Expansion [ Time Frame: Approximately 2 years ]
    Determination of a safe and tolerable Recommended Phase 2 Dose (RP2D)
  • Incidence of Dose Limiting Toxicities in in Dose Escalation and Cohort Expansion [ Time Frame: Approximately 2 years ]
    Determine safety and tolerability
  • ORR as measured by stable disease (SD), partial response (PR), and complete response (CR) by radiographic assessment [ Time Frame: Approximately 2 years ]
    Disease response will be assessed using a combination of physical exam and imaging
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 19, 2020)
  • Single-dose and steady-state Cmax of VRx-3996 and valganciclovir [ Time Frame: Through study completion, an average of 6 months ]
    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 C2 D1 and pre-dose and at hour 2 on C1D2 ,C1D15, and C2D15.
  • Single-dose and steady-state AUC of VRx-3996 and valganciclovir [ Time Frame: Through study completion, an average of 6 months ]
    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 C2 D1 and pre-dose and at hour 2 on C1D2 ,C1D15, and C2D15.
  • Steady-state elimination half-life of VRx-3996 and valganciclovir [ Time Frame: Through study completion, an average of 6 months ]
    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 C2 D1 and pre-dose and at hour 2 on C1D2, C1D15, and C2D15.
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2018)
  • Single-dose and steady-state Cmax of VRx-3996 and valganciclovir [ Time Frame: Through study completion, an average of 6 months ]
    PK assessment of both VRx-3996 and valganciclovir at 0, 1, 1.5, 2, 3, 5 and 7 hours post-dose on C1D1 and pre-dose on Day 1 of all following cycles
  • Single-dose and steady-state AUC of VRx-3996 and valganciclovir [ Time Frame: Through study completion, an average of 6 months ]
    PK assessment of both VRx-3996 and valganciclovir at 0, 1, 1.5, 2, 3, 5 and 7 hours post-dose on C1D1 and pre-dose on Day 1 of all following cycles
  • Steady-state elimination half-life of VRx-3996 and valganciclovir [ Time Frame: Through study completion, an average of 6 months ]
    PK assessment of both VRx-3996 and valganciclovir at 0, 1, 1.5, 2, 3, 5 and 7 hours post-dose on C1D1 and pre-dose on Day 1 of all following cycles
  • 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
  • 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 the study drug administration) to the date of disease progression
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose Escalation & Expansion Study of Oral VRx-3996 & Valganciclovir in Subjects With EBV-Associated Lymphoid Malignancies
Official Title  ICMJE 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
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Phase 1: dose escalation phase (3+3 design with definitions of dose limiting toxicity) to define a recommended phase 2 dose

Phase 2: dose expansion

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Epstein-Barr Virus Associated Lymphoma
  • Lymphoproliferative Disorders
Intervention  ICMJE
  • Drug: VRx-3996
    capsules taken orally once or twice daily
  • Drug: Valganciclovir
    tablets taken orally once or twice daily
Study Arms  ICMJE
  • 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

    Interventions:
    • Drug: VRx-3996
    • Drug: Valganciclovir
  • Experimental: Phase 2 Dose Expansion
    VRx-3996 (RP2D: recommended phase 2 dose) and valganciclovir
    Interventions:
    • Drug: VRx-3996
    • Drug: Valganciclovir
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 19, 2020)
80
Original Estimated Enrollment  ICMJE
 (submitted: January 10, 2018)
45
Estimated Study Completion Date  ICMJE August 2021
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Robert McRae, Vice President, Operations 858-400-8470 ClinicalTrials@Viracta.com
Listed Location Countries  ICMJE Brazil,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03397706
Other Study ID Numbers  ICMJE VT3996-201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Viracta Therapeutics, Inc.
Study Sponsor  ICMJE Viracta Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Robert McRae Viracta Therapeutics, Inc.
PRS Account Viracta Therapeutics, Inc.
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP