Clinical Trials /

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

NCT03397706

Description:

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.

Related Conditions:
  • Hematopoietic and Lymphoid Malignancy
  • Lymphoproliferative Disorder
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: VT3996-201
  • NCT ID: NCT03397706

Conditions

  • Epstein-Barr Virus Associated Lymphoma
  • Lymphoproliferative Disorders

Interventions

DrugSynonymsArms
VRx-3996Phase 1b Dose Escalation
ValganciclovirPhase 1b Dose Escalation

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1b Dose EscalationExperimentalVRx-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
  • VRx-3996
  • Valganciclovir
Phase 2 Dose ExpansionExperimentalVRx-3996 (RP2D: recommended phase 2 dose) and valganciclovir
  • VRx-3996
  • Valganciclovir

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Adverse Events and changes in clinical safety laboratory values in Dose Escalation and Cohort Expansion
Time Frame:Approximately 2 years
Safety Issue:
Description:Determination of a safe and tolerable Recommended Phase 2 Dose (RP2D)

Secondary Outcome Measures

Measure:Single-dose and steady-state Cmax of VRx-3996 and valganciclovir
Time Frame:Through study completion, an average of 6 months
Safety Issue:
Description: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
Measure:Single-dose and steady-state AUC of VRx-3996 and valganciclovir
Time Frame:Through study completion, an average of 6 months
Safety Issue:
Description: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
Measure:Steady-state Elimination half-life of VRx-3996 and valganciclovir
Time Frame:Through study completion, an average of 6 months
Safety Issue:
Description: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
Measure:Time to response
Time Frame:Approximately 6 months
Safety Issue:
Description: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
Measure:Duration of response
Time Frame:Up to approximately 2 years
Safety Issue:
Description: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
Measure:Progression-free survival
Time Frame:Up to approximately 2 years
Safety Issue:
Description:The interval between the date of first study drug administration and the date of PD or death, whichever is first reported

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Viracta Therapeutics, Inc.

Trial Keywords

  • EBV+ post-transplant lymphoproliferative malignancy
  • EBV-associated lymphoproliferative disorders associated with acquired immunodeficiency including HIV-positive
  • Relapsed, refractory, EBV+ lymphoid malignancy

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