Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

A Study of PLX51107 in Advanced Malignancies

Protocol: OSU-16056

Full Title

A Phase 1b Dose Escalation Study to Assess Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PLX51107 in Subjects with Advanced Malignancies

Purpose

The purpose of this research study is to evaluate safety, pharmacokinetics,

pharmacodynamics, and preliminary efficacy of the investigational drug PLX51107 in subjects

with advanced solid tumors (including lymphoma), acute myeloid leukemia (AML), or high-risk

myelodysplastic syndrome (MDS).

Are you eligible?

Inclusion Criteria:

Confirmed diagnosis of an advanced malignancy in one of two treatment groups:

Treatment Group A: any advanced solid tumor (including lymphomas); Treatment Group B:

relapsed or refractory AML or high-risk MDS, defined as IPSS INT-2 or greater disease

(Maes 1999).

Progressed following at least 1 line of prior anti-cancer therapy for the advanced

disease and there is no further standard therapeutic option available (including

subjects who are intolerant to the approved/available therapies)

Age ≥ 18 years

Eastern Cooperative Oncology Group (ECOG) performance Status (PS) 0-2

Life expectancy ≥ 3 months

Adequate organ function as demonstrated by the following laboratory values (collected

within 10 days of treatment initiation) and as appropriate for the disease under

study.

Women of child-bearing potential must have a negative serum pregnancy test at

Screening and must agree to use an effective form of contraception from the time of

the negative pregnancy test up to 6 months after the last dose of study drug. Women

of non-child-bearing potential may be included if they are either surgically sterile

or have been postmenopausal for ≥ 1 year.

Fertile men must agree to use an effective method of birth control during the study

and for up to 6 months after the last dose of study drug

All associated toxicity, except grade 2 alopecia, from previous cancer therapy must

be resolved (to ≤ Grade 1 or Baseline) prior to study treatment administration (Grade

2 alopecia is allowed).

Willingness and ability to provide written informed consent prior to any

study-related procedures and to comply with all study requirements.

Exclusion Criteria:

Prior exposure to a bromodomain inhibitor

Active graft versus host disease

Known uncontrolled fungal, bacterial, and/or viral infection ≥ Grade 2

Uncontrolled autoimmune hemolytic anemia or thrombocytopenia

Presence of symptomatic or uncontrolled central nervous system or leptomeningeal

metastases (Note: Subjects with stable, treated brain metastases are eligible for

this trial. However, subjects must not have required steroid treatment for their

brain metastases within 30 days of Screening.)

A diagnosis of acute promyelocytic leukemia (APL) or chronic myeloid leukemia (CML)

in blast crisis

Known or suspected allergy to the investigational agent or any agent given in

association with this trial

Clinically significant cardiac arrhythmias including brady-arrhythmias and/or

subjects who require anti-arrhythmic therapy (excluding beta blockers or digoxin).

Subjects with controlled atrial fibrillation are not excluded.

Congenital long QT syndrome or subjects taking concomitant medications known to

prolong the QT interval except treatment required for infections with a low risk of

QTc prolongation.

Subjects on active anticoagulation therapy including warfarin, factor Xa inhibitors,

thrombin inhibitors or heparin

QTcF ≥ 450 msec (for males) or ≥ 470 msec (for females) at Screening

History of clinically significant cardiac disease or congestive heart failure >New

York Heart Association (NYHA) class 2. Subjects must not have unstable angina

(anginal symptoms at rest) or new-onset angina within the last 3 months or myocardial

infarction within the past 6 months.

Hypertension as defined by systolic blood pressure > 150 mmHg or diastolic blood

pressure > 90 mmHg despite optimal medical management

Arterial or venous thrombotic or embolic events such as cerebrovascular accident

(including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism

within the 6 months before start of study medication (except for adequately treated

catheter-related venous thrombosis occurring more than 1 month before the start of

study medication)

Inability to take oral medication or significant nausea and vomiting, malabsorption,

or significant small bowel resection that, in the opinion of the Investigator, would

preclude adequate absorption

Non-healing wound, ulcer, or bone fracture

Known HIV-positive individuals on combination antiretroviral therapy

Subjects with known active hepatitis B or C, or chronic hepatitis B or C requiring

treatment with antiviral therapy

Presence of any psychological, familial, sociological or geographical condition

potentially hampering compliance with the study protocol

Strong CYP3A4 and 2C8 inhibitors or inducers or CYP3A4 substrate drugs with a narrow

therapeutic range within 14 days or 5 drug half-lives, whichever is longer, before

start of study drug

Subjects with > Grade 1 serum potassium, magnesium, or calcium levels

Active secondary malignancy (either concurrent or within the last 3 years) that

requires non-surgical therapy (e.g., chemotherapy or radiation therapy), with the

exception of surgically treated basal or squamous cell carcinoma of the skin,

melanoma in-situ, or carcinoma in-situ of the cervix

Major surgery or significant traumatic injury within 14 days prior to Cycle 1 Day 1

Receipt of anti-cancer medications or investigational drugs within the following

interval before the first administration of study drug:

< 14 days or 5 drug half-lives, whichever is shorter, for chemotherapy and

investigational agents

< 5 half-lives for all other anti-cancer medications, or Sponsor approval

leukopheresis and/or hydroxyurea for leukocytosis is allowed any time prior to

and during the study to reduce WBC

Radiation therapy within 14 days prior to Cycle 1 Day 1

Any medical condition(s) that, in the opinion of the Investigator, would interfere

with the study endpoints or the subject's ability to participate in the study

Acute Myeloid Leukemia Leukemia