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A Study of PLX51107 in Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT02683395
Recruitment Status : Terminated (Business Decision)
First Posted : February 17, 2016
Last Update Posted : December 24, 2018
Sponsor:
Information provided by (Responsible Party):
Plexxikon

Brief Summary:
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), and advanced hematological malignancies

Condition or disease Intervention/treatment Phase
Solid Tumors Acute Myeloid Leukemia Myelodysplastic Syndrome Non-Hodgkin's Lymphoma Drug: PLX51107 Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2a, Two-Part, Dose Escalation and Expansion Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PLX51107 in Subjects With Advanced Hematological Malignancies and Solid Tumors
Study Start Date : March 2016
Actual Primary Completion Date : September 2018
Actual Study Completion Date : September 2018


Arm Intervention/treatment
Experimental: Treatment Group A
Open label, sequential PLX51107 dose escalation in approximately 30 solid tumor subjects.
Drug: PLX51107
Experimental: Treatment Group B
Open label, sequential PLX51107 dose escalation in approximately 30 subjects with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS).
Drug: PLX51107



Primary Outcome Measures :
  1. Safety of PLX51107 as measured by adverse events and serious adverse events. [ Time Frame: 1 year ]
  2. Area under the concentration-time curve (AUC) of PLX51107. [ Time Frame: 1 year ]
  3. Maximum observed concentration (Cmax) of PLX51107. [ Time Frame: 1 year ]
  4. Time to peak concentration (Tmax) of PLX51107. [ Time Frame: 1 year ]
  5. Half life (t1/2) of PLX51107. [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 1 year ]
    ORR is defined as the total number of patients with the best overall response according to standard criteria for the relevant malignancy divided by the total number of treated patients and expressed as a percentage.

  2. Duration Of Response (DOR). [ Time Frame: 1 year ]
    DOR is defined as the time from the initial objective response to disease progression or death, whichever occurs first.

  3. Progression-Free Survival (PFS). [ Time Frame: 1 year ]
    PFS time is defined as the time from the first dose of PLX51107 to disease progression or death, whichever occurs first.

  4. Overall Survival (OS). [ Time Frame: 1 year ]
    OS is defined as the first dose of study drug until the date of death from any cause.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Confirmed diagnosis of a relapsed or refractory malignancy in 1 of 2 treatment groups:

    1. Group A: Subjects with any solid tumor (including lymphomas).
    2. Group B: Subjects with relapsed or refractory AML, Subjects with relapsed or refractory high-risk MDS, defined as revised International Prognostic Scoring System (IPSS-R) intermediate or greater disease.
  2. Age ≥18 years.
  3. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
  4. Life expectancy ≥3 months in the judgment of the investigator.
  5. Adequate organ function.
  6. Group A subjects must have measurable or evaluable disease per the appropriate disease criteria.
  7. 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. Effective forms of contraception include abstinence, hormonal contraceptive 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.
  8. 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.
  9. All associated clinically significant toxicity from previous cancer therapy must be resolved (to ≤Grade 1 or baseline) prior to study treatment administration (Grade 2 alopecia is allowed).
  10. 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 exposure to a bromodomain inhibitor, such as OTX-015 or CPI-0610.
  2. Allogenic or autologous transplant for hematological malignancy with infusion of stem cells within 90 days before Cycle 1 Day 1, or on active immunosuppressive therapy for graft-versus-host disease (GVHD) or GVHD prophylaxis within 2 weeks of Cycle 1 Day 1.
  3. Known uncontrolled fungal, bacterial, and/or viral infection ≥Grade 2.
  4. Uncontrolled autoimmune hemolytic anemia or thrombocytopenia.
  5. For Group A: Subjects with a history of brain metastases are ineligible. This includes previously treated brain metastases. For Group B (subjects with AML): Active symptomatic CNS involvement of AML. Subjects with previously treated leptomeningeal disease that has been effectively treated are eligible.
  6. A diagnosis of acute promyelocytic leukemia (APL) or chronic myeloid leukemia (CML) in blast crisis.
  7. Known or suspected allergy to the investigational agent or any agent given in association with this trial.
  8. Women who are pregnant or are 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. Subject with known human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection or is known to be a carrier of hepatitis B or C.
  12. Strong CYP3A4 and CYP2C8 inhibitors or inducers or CYP3A4 substrate drugs with a narrow therapeutic range taken within 14 days or 5 drug half-lives before start of study drug.
  13. Active secondary malignancy
  14. Major surgery or significant traumatic injury within 14 days prior to therapy
  15. Receipt of anti-cancer therapy 14 days prior to Cycle 1 Day 1
  16. Presence of any other medical, psychological, familial, sociological, or geographic condition potentially hampering compliance with the study protocol Subjects who are participating in any other therapeutic clinical study (observational or registry trials are allowed).
  17. Subjects who have Burkitt's lymphoma or Burkitt-like lymphoma.
  18. Subjects on active anticoagulation therapy including warfarin, factor Xa inhibitors, thrombin inhibitors, or heparin.
  19. Subjects with documented hepatic metastases involving >50% of the hepatic parenchyma.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02683395


Locations
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, Ohio
The Ohio State University Stephanie Spielman Comprehensive Breast Center
Columbus, Ohio, United States, 43212
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
United States, South Carolina
MUSC/ Hollings Cancer Center
Charleston, South Carolina, United States, 29425
United States, Texas
South Texas Accelerated Research Therapeutics
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Plexxikon

Responsible Party: Plexxikon
ClinicalTrials.gov Identifier: NCT02683395     History of Changes
Other Study ID Numbers: PLX122-01
First Posted: February 17, 2016    Key Record Dates
Last Update Posted: December 24, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Plexxikon:
PLX51107
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Non-Hodgkin's Lymphoma

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Non-Hodgkin
Leukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoma
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases