A Study of PLX2853 in Relapsed or Refractory Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

NCT03787498 | Completed Phase 1 FDA Drug

• 1 other identifier: PLX124-02
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this research study is to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of the investigational drug PLX2853 in subjects with Relapsed or Refractory Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome

Conditions

Relapsed Acute Myeloid Leukemia (AML); Refractory Acute Myeloid Leukemia (AML); High-risk Myelodysplastic Syndrome (MDS)

Keywords

PLX2853; Acute Myeloid Leukemia; AML; Myelodysplastic Syndrome; MDS; Hematologic Malignancy; Blood Cancer

Outcome Measures

Primary Outcomes (7)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  First dose of study drug through at least 30 days after end of treatment

• Area under the concentration-time curve (AUC) of PLX2853

  From first dose of PLX2853 up to 30 days after end of treatment

• Maximum observed concentration (Cmax) of PLX2853

  From first dose of PLX2853 up to 30 days after end of treatment

• Time to peak concentration (Tmax) of PLX2853

  From first dose of PLX2853 up to 30 days after end of treatment

• Half life (t1/2) of PLX2853

  From first dose of PLX2853 up to 30 days after end of treatment

• Terminal elimination rate constant (Kel)

  From first dose of PLX2853 up to 30 days after end of treatment

• Number of participants who experience dose limiting toxicity as defined in the protocol

  Dose escalation will be guided by a modified continuous reassessment method (mCRM) using a Bayesian logistic regression model that follows the escalation with overdose control (EWOC) principle. In this method, a decision to escalate to the next dose level is based on a review of all subjects who have completed the DLT observation period.

  up to 18 months

Secondary Outcomes (6)

• Overall complete remission (OCR) rate

  From the first dose of study drug until the date of documented best response to treatment, assessed up to 18 months

• Overall response rate (ORR)

  From the first dose of study drug until the date of documented response to treatment, assessed up to 18 months

• Duration of response (DOR)

  DOR defined as the time from the initial objective response to disease progression or death, whichever occurs first, assessed up to 18 months

• Event-free survival (EFS)

  EFS time is defined as the time from the first dose of PLX2853 to treatment failure, relapse after initial response or death from any cause, assessed up to 18 months.

• Progression-free survival (PFS)

  PFS time is defined as the time from the first dose of PLX2853 to disease progression or death, whichever occurs first, assessed up to 18 months.

Study Arms (1)

PLX2853

EXPERIMENTAL

Approximately 30 subjects will be enrolled as part of dose escalation to identify the MTD/RP2D of PLX2853. Up to 6 additional subjects may be enrolled at the MTD/RP2D to further characterize the PK and PDy of PLX2853.

Drug: PLX2853

Interventions

PLX2853 DRUG

Tablets

PLX2853

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of one of the following myeloid malignancies, based on the 2016 revision of the World Health Organization classification:
• A. Relapsed or refractory AML.
• I. Subjects must have received no more than 3 prior induction therapies and have no standard therapeutic option that is expected to result in a clinical benefit.
• B. Relapsed or refractory MDS.
• I. Subjects must have high-risk disease (intermediate or greater disease according to the revised International Prognostic Scoring System \[IPSS-R\]).
• II. Subjects must have received no more than 3 prior therapies, 1 of which must have included a hypomethylating agent such as azacytidine or decitabine.
• III. Subjects must have no standard therapeutic option that is expected to result in a clinical benefit.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
• Life expectancy of ≥3 months in the judgment of the investigator.
• Adequate renal, hepatic, and coagulation parameters:
• A. Measured or calculated (Cockcroft-Gault formula) creatinine clearance (CrCl) ≥60 mL/min.
• B. Total bilirubin ≤1.5 × ULN unless due to Gilbert's syndrome.
• C. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN.
• D. Prothrombin time or international normalized ratio ≤1.5 × ULN.

You may not qualify if:

• Prior treatment with a bromodomain inhibitor.
• Any one of the following therapies:
• A. Stem cell transplantation within 90 days of study drug initiation;
• B. Active immunosuppressive therapy for graft-versus-host disease (GVHD);
• C. GVHD prophylaxis within 2 weeks of study drug initiation.
• Known uncontrolled fungal, bacterial, and/or viral infection ≥Grade 2.
• Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia.
• Active symptomatic central nervous system involvement of AML. (Individuals who have had leptomeningeal disease that was effectively treated are eligible.)
• A diagnosis of acute promyelocytic leukemia or chronic myeloid leukemia in blast crisis.
• Known or suspected allergy to the study drug or any agent given in association with this trial.
• Women who are either pregnant or breast feeding.
• Clinically significant cardiac disease.
• 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.
• Individuals who are known to be infected with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) or are known carriers of HBV or HCV. Individuals who are positive for HCV antibody must be negative for HCV RNA by polymerase chain reaction (PCR) to be eligible. Individuals with occult or prior HBV infection (defined as being seropositive for total hepatitis B core antibody and seronegative for hepatitis B surface antigen) may be included if HBV DNA is undetectable. These individuals must be willing to undergo additional testing per local standard of care.
• Active second malignancy with the exception of any of the following:

Sponsors & Collaborators

• Opna Bio LLC: lead

Study Sites (6)

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Sidney Kimmel Comprehensive Cancer At Johns Hopkins

Baltimore, Maryland, 27287, United States

Location

NewYork-Presbyterian / Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Oregon Health and Sciences University

Portland, Oregon, 97239, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Neoplasms by Site

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2018
• First Posted: December 26, 2018
• Study Start: March 19, 2019
• Primary Completion: June 30, 2021
• Study Completion: June 30, 2021
• Last Updated: April 12, 2022

Record last verified: 2022-04

Locations

US (6)