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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 10, 2020
Sponsor:
Information provided by (Responsible Party):
Viracta Therapeutics, Inc.

Study Description
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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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 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
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 : February 2021
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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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
capsules taken orally once or twice daily

Drug: Valganciclovir
tablets taken orally once or twice daily
Experimental: Phase 2 Dose Expansion
VRx-3996 (RP2D: recommended phase 2 dose) and valganciclovir
 Drug: VRx-3996
capsules taken orally once or twice daily

Drug: Valganciclovir
tablets taken orally once or twice daily


Outcome Measures
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Primary Outcome Measures :
  1. 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)

  2. Incidence of Dose Limiting Toxicities in Dose Escalation and Cohort Expansion [ Time Frame: Approximately 2 years ]
    Determine safety and tolerability

  3. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  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
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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

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
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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): NCT03397706


Contacts
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Contact: Robert McRae, Vice President, Operations 858-400-8470 ClinicalTrials@Viracta.com

Locations
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Sponsors and Collaborators
Viracta Therapeutics, Inc.
Investigators
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Study Director: Robert McRae Viracta Therapeutics, Inc.
More Information
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Additional Information:

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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 10, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
 Immune System Diseases
Valganciclovir
Antiviral Agents
Anti-Infective Agents