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.
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
| Drug | Synonyms | Arms |
|---|
| VRx-3996 | Nanatinostat | PK Cohort |
| Valganciclovir | | PK Cohort |
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. Following completion of the Ph2, the
study will enroll additional patients into a PK cohort to investigate the PK parameters of
the tablet formulation.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Phase 1b Dose Escalation | Experimental | 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 | |
| Phase 2 Dose Expansion | Experimental | VRx-3996 (RP2D: recommended phase 2 dose) and valganciclovir | |
| PK Cohort | Experimental | Assessment of VRx-3996 tablet and valganciclovir PK parameters at the RP2D | |
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
- Known history of HHV-6 chromosomal integration
- Known history of HIV infection
| 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: | Up to 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 Cycle 2 Day 15 (each cycle is 28 days) |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Single-dose and steady-state AUC of VRx-3996 and valganciclovir |
| Time Frame: | Through Cycle 2 Day 15 (each cycle is 28 days) |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Steady-state elimination half-life of VRx-3996 and valganciclovir |
| Time Frame: | Through Cycle 2 Day 15 (each cycle is 28 days) |
| Safety Issue: | |
| Description: | 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 |
| 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 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
- Relapsed, refractory, EBV+ lymphoid malignancy
Last Updated
July 28, 2021
