Clinical Trials /

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

NCT03787498

Description:

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

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of PLX2853 in Relapsed or Refractory Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome
  • Official Title: A Phase 1b Dose-escalation Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PLX2853 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome

Clinical Trial IDs

  • ORG STUDY ID: PLX124-02
  • NCT ID: NCT03787498

Conditions

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

Interventions

DrugSynonymsArms
PLX2853PLX2853

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
PLX2853ExperimentalApproximately 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.
  • PLX2853

Eligibility Criteria

        Inclusion Criteria:

          1. 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.

          2. Age ≥18 years.

          3. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.

          4. Life expectancy of ≥3 months in the judgment of the investigator.

          5. 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. E. Activated partial
             thromboplastin time ≤1.5 × ULN.

          6. Women of child-bearing potential must have a negative pregnancy test at Screening and
             must agree to use an effective form of contraception from the time of the negative
             pregnancy test to 90 days after the last dose of study drug. Effective forms of
             contraception include abstinence, hormonal contraception in conjunction with a barrier
             method, or a double barrier method. Women of non-child-bearing potential may be
             included if they are either surgically sterile or have been postmenopausal for ≥ 1
             year.

          7. Fertile men must agree to use an effective method of birth control during the study
             and for 90 days after the last dose of study drug.

          8. Resolution (to ≤Grade 1 or baseline) of all significant toxicity associated with prior
             cancer therapy prior to study drug initiation. (Grade 2 alopecia is allowed.)

          9. Willingness and ability to provide written informed consent prior to any study-related
             procedures and to comply with all study requirements.

        Exclusion Criteria:

          1. Prior treatment with a bromodomain inhibitor.

          2. 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.

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

          4. Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia.

          5. Active symptomatic central nervous system involvement of AML. (Individuals who have
             had leptomeningeal disease that was effectively treated are eligible.)

          6. A diagnosis of acute promyelocytic leukemia or chronic myeloid leukemia in blast
             crisis.

          7. Known or suspected allergy to the study drug or any agent given in association with
             this trial.

          8. Women who are either pregnant or breast feeding.

          9. Clinically significant cardiac disease.

         10. 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.

         11. 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.

         12. Active secondary malignancy that confounds interpretation of the study results or
             limits the subject's survival to <2 years in the judgement of the investigator.

         13. Major surgery or significant injury within the 14-day period prior to study drug
             initiation.

         14. Anti-cancer therapy in the period immediately preceding study drug initiation.

         15. Any other medical, psychological, familial, sociologic, or geographic condition that,
             in the judgement of the investigator, would potentially hamper compliance with the
             study protocol or interfere with the study endpoints or the subject's ability to
             participate in the study.

         16. Participation in any other therapeutic clinical study. (Participation in observational
             or registry trials is allowed.)

         17. Individuals who are on active anticoagulation therapy (e.g., warfarin, factor Xa
             inhibitors, thrombin inhibitors, heparin).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame:First dose of study drug through at least 30 days after end of treatment
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Overall complete remission (OCR) rate
Time Frame:From the first dose of study drug until the date of documented best response to treatment, assessed up to 18 months
Safety Issue:
Description:AML — CR + CRi; MDS — CR
Measure:Overall response rate (ORR)
Time Frame:From the first dose of study drug until the date of documented response to treatment, assessed up to 18 months
Safety Issue:
Description:AML — Complete response (CR) + CR with incomplete hematologic recovery (CRi) + partial response (PR); MDS — CR + PR
Measure:Duration of response (DOR)
Time Frame:DOR defined as the time from the initial objective response to disease progression or death, whichever occurs first, assessed up to 18 months
Safety Issue:
Description:
Measure:Event-free survival (EFS)
Time Frame: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.
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame: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.
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:From the first dose of study drug until the date of death from any cause, assessed up to 18 months.
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Plexxikon

Trial Keywords

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

Last Updated

January 8, 2020