NCT03397706 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2025-03-20

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 Epstein-Barr Virus Associated Lymphoma (EBV+ lymphomas).

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number (Proportion) of Participants With Adverse Events (AEs)

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outcome · POSTED

Number (Proportion) of Participants With Dose-Limiting Toxicities (DLTs) in Phase 1b

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outcome · POSTED

Overall Response Rate

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outcome · POSTED

Duration of Response

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outcome · POSTED

Time to Response

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outcome · POSTED

Progression-Free Survival

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outcome · POSTED

Disease Control Rate

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outcome · POSTED

Overall Survival

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outcome · POSTED

Cmax (ng/mL) of VRx-3996

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outcome · POSTED

Cmax (ng/mL) of Valganciclovir

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outcome · POSTED

Area Under Curve (AUC) 0-t of VRx-3996

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outcome · POSTED

AUC 0-t of of Valganciclovir

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outcome · POSTED

Half-life of VRx-3996

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outcome · POSTED

Half-life of Valganciclovir

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Key Inclusion Criteria: * Relapsed/refractory, pathologically confirmed Epstein-Barr Virus positive (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 central nervous system (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 quantitative polymerase chain reaction (qPCR) * Known history of human herpes virus (HHV)-6 chromosomal integration * Known history of HIV infection
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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
intervention Names
Combination Product: VRx-3996 and valganciclovir
label
Phase 1b Dose Escalation
type
EXPERIMENTAL
description
VRx-3996 and valganciclovir at the recommended Phase 2 dose (RP2D)
intervention Names
Combination Product: VRx-3996 and valganciclovir
label
Phase 2 Expansion - Capsule
type
EXPERIMENTAL
description
VRx-3996 and valganciclovir at the recommended Phase 2 dose (RP2D)
intervention Names
Combination Product: VRx-3996 and valganciclovir
label
Phase 2 Expansion - Tablet
type
EXPERIMENTAL

interventions

arm Group Labels
Phase 1b Dose Escalation
Phase 2 Expansion - Capsule
Phase 2 Expansion - Tablet
description
second-generation histone deacetylase (HDAC) inhibitor, nanatinostat (previously referred to as either VRx-3996 or CHR-3396)
name
VRx-3996 and valganciclovir
other Names
nanatinostat
ganciclovir
Chroma (CHR)-3996
type
COMBINATION_PRODUCT

Study design

allocation

NON_RANDOMIZED

intervention Model

SEQUENTIAL

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 Tablet PK Cohort

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 64
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Number (percentage) of patients experiencing at least one treatment-emergent adverse event, defined as those untoward medical events with onset after the first dose of study drug or existing events that worsened after the first dose during the study
measure
Number (Proportion) of Participants With Adverse Events (AEs)
time Frame
Up to approximately 2 years
description
Number (percentage) of patients experiencing a DLT during the first cycle (28 days) of study treatment in Phase 1b, defined as an adverse event (AE) or clinically significant abnormal laboratory value that was at least possibly related to study drugs and was not primarily related to disease, disease progression, concomitant medication(s), or intercurrent illness. In addition, to be considered a DLT, the AE had to meet at least one of the following criteria: * Grade 4 anemia unexplained by underlying disease * Grade 4 febrile neutropenia * Grade 4 neutropenia lasting \>5 days * Any other Grade 4 hematologic toxicity (thrombocytopenia, neutropenia, febrile neutropenia, anemia) of any duration * Grade 4 or higher tumor lysis syndrome * Grade 3 or higher thrombocytopenia (with or without bleeding) * Any requirement for platelet transfusion * Grade 3 or higher non-hematologic toxicity despite adequate supportive care * Results in a dose hold of \>7 consecutive days
measure
Number (Proportion) of Participants With Dose-Limiting Toxicities (DLTs) in Phase 1b
time Frame
Cycle 1 (28 days)
description
Number (percentage) of patients with a best overall complete response (CR) or partial response (PR) according to the Lugano 2014 criteria (Cheson, Bruce D. et al. J Clin Oncology 2014;32(27):3059-68), where CR included complete metabolic response (no/minimal fluorodeoxyglucose \[FDG\] uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions, and PR included partial metabolic response (reduced FDG uptake compared with baseline) or radiologic response (target lesions ≤ 50% decrease in the sum of the product of perpendicular diameters of up to 6 target measurable nodes and extranodal sites)
measure
Overall Response Rate
time Frame
Up to approximately 2 years

secondary Outcomes

description
Interval of time from date of first observed complete or partial response per Lugano 2014 criteria (Cheson BD et al. J Clin Oncology 2014;32(27):3059-68) to the date of documented disease progression or death due to any cause, where disease progression is defined by Lugano 2014 criteria (Cheson BD et al. J Clin Oncology 2014;32(27):3059-68) as progressive metabolic disease (increase in fluorodeoxyglucose \[FDG\] uptake from baseline or new FDG-avid foci consistent with lymphoma) or progressive radiologic response (increase in the product of perpendicular diameters of a single node by ≥ 50% or emergence of a new lesion)
measure
Duration of Response
time Frame
Up to approximately 2 years
description
Interval of time from the start of study drug treatment to the first documentation of CR or PR per Lugano 2014 criteria (Cheson BD et al. J Clin Oncology 2014;32(27):3059-68)
measure
Time to Response
time Frame
Up to approximately 2 years
description
Interval of time from the date of first study drug administration to the documented date of disease progression or death, whichever occurred first, where disease progression is defined by Lugano 2014 criteria (Cheson BD et al. J Clin Oncology 2014;32(27):3059-68) as progressive metabolic disease (increase in fluorodeoxyglucose \[FDG\] uptake from baseline or new FDG-avid foci consistent with lymphoma) or progressive radiologic response (increase in the product of perpendicular diameters of a single node by ≥ 50% or emergence of a new lesion)
measure
Progression-Free Survival
time Frame
Up to approximately 2 years
description
Number (percentage) of patients with CR, PR, or stable disease (SD) per Lugano 2014 criteria (Cheson BD et al. J Clin Oncology 2014;32(27):3059-68)
measure
Disease Control Rate
time Frame
Up to approximately 2 years
description
Interval of time from date of first study drug treatment to date of death, for any reason (patients without documentation of death at the time of analysis were censored at the date the patient was last known to be alive)
measure
Overall Survival
time Frame
Up to approximately 2 years
description
Pharmacokinetic (PK) assessment of VRx-3996 pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on cycle 1 day 1 (C1D1) and cycle 2 day 2 (C2D1)
measure
Cmax (ng/mL) of VRx-3996
time Frame
Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1
description
PK assessment of valganciclovir pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1D1 and C2D1
measure
Cmax (ng/mL) of Valganciclovir
time Frame
Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1
description
PK assessment of VRx-3996 pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1D1 and C2D1
measure
Area Under Curve (AUC) 0-t of VRx-3996
time Frame
Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1
description
PK assessment of valganciclovir pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1D1 and C2D1
measure
AUC 0-t of of Valganciclovir
time Frame
Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1
description
PK assessment of VRx-3996 pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1D1 and C2D1
measure
Half-life of VRx-3996
time Frame
Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1
description
PK assessment of valganciclovir pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1D1 and C2D1
measure
Half-life of Valganciclovir
time Frame
Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1

Full study description

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 Epstein-Barr Virus Associated Lymphoma (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 Tablet Pharmacokinetic (PK) cohort to investigate the PK parameters of the tablet formulation.

Source references

references

citation
Haverkos B, Alpdogan O, Baiocchi R, Brammer JE, Feldman TA, Capra M, Brem EA, Nair S, Scheinberg P, Pereira J, Shune L, Joffe E, Young P, Spruill S, Katkov A, McRae R, Royston I, Faller DV, Rojkjaer L, Porcu P. Targeted therapy with nanatinostat and valganciclovir in recurrent EBV-positive lymphoid malignancies: a phase 1b/2 study. Blood Adv. 2023 Oct 24;7(20):6339-6350. doi: 10.1182/bloodadvances.2023010330.
pmid
37530631
type
DERIVED