Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03397706
Recruitment Status : Recruiting
First Posted : January 12, 2018
Last Update Posted : July 28, 2021
Sponsor:
Information provided by (Responsible Party):
Viracta Therapeutics, Inc.

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Epstein-Barr Virus Associated Lymphoma Lymphoproliferative Disorders Drug: VRx-3996 Drug: Valganciclovir Phase 1 Phase 2

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
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

PK Cohort
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 29, 2018
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

 Drug: VRx-3996
Taken orally once or twice daily
Other Name: Nanatinostat

Drug: Valganciclovir
Taken orally once or twice daily
Experimental: Phase 2 Dose Expansion
VRx-3996 (RP2D: recommended phase 2 dose) and valganciclovir
 Drug: VRx-3996
Taken orally once or twice daily
Other Name: Nanatinostat

Drug: Valganciclovir
Taken orally once or twice daily
Experimental: PK Cohort
Assessment of VRx-3996 tablet and valganciclovir PK parameters at the RP2D
 Drug: VRx-3996
Taken orally once or twice daily
Other Name: Nanatinostat

Drug: Valganciclovir
Taken orally once or twice daily


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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)

  2. Incidence of Dose Limiting Toxicities in Dose Escalation and Cohort Expansion [ Time Frame: Up to approximately 2 years ]
  3. ORR as measured by stable disease (SD), partial response (PR), and complete response (CR) by radiographic assessment [ Time Frame: Up to approximately 2 years ]

Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT03397706


Contacts
Layout table for location contacts
Contact: Robert McRae, Vice President, Operations 858-400-8470 ClinicalTrials@Viracta.com

Locations
Show Show 28 study locations
Sponsors and Collaborators
Viracta Therapeutics, Inc.
Investigators
Layout table for investigator information
Study Director: Robert McRae Viracta Therapeutics
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Layout table for additonal information
Responsible Party: Viracta Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03397706    
Other Study ID Numbers: VT3996-201
First Posted: January 12, 2018    Key Record Dates
Last Update Posted: July 28, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Viracta Therapeutics, Inc.:
EBV+ post-transplant lymphoproliferative malignancy
EBV-associated lymphoproliferative disorders associated with acquired immunodeficiency
Relapsed, refractory, EBV+ lymphoid malignancy
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
 Immune System Diseases
Valganciclovir
Antiviral Agents
Anti-Infective Agents