A Study of PLX51107 in Advanced Malignancies

NCT02683395 | Terminated Phase 1

• 1 other identifier: PLX122-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 5

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

Conditions

Solid Tumors; Acute Myeloid Leukemia; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma

Keywords

PLX51107; Acute Myeloid Leukemia; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (5)

• Safety of PLX51107 as measured by adverse events and serious adverse events.

  1 year

• Area under the concentration-time curve (AUC) of PLX51107.

  1 year

• Maximum observed concentration (Cmax) of PLX51107.

  1 year

• Time to peak concentration (Tmax) of PLX51107.

  1 year

• Half life (t1/2) of PLX51107.

  1 year

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  1 year

• Duration Of Response (DOR).

  1 year

• Progression-Free Survival (PFS).

  1 year

• Overall Survival (OS).

  1 year

Study Arms (2)

Treatment Group A

EXPERIMENTAL

Open label, sequential PLX51107 dose escalation in approximately 30 solid tumor subjects.

Drug: PLX51107

Treatment Group B

EXPERIMENTAL

Open label, sequential PLX51107 dose escalation in approximately 30 subjects with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS).

Drug: PLX51107

Interventions

PLX51107 DRUG

Treatment Group A; Treatment Group B

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 a relapsed or refractory malignancy in 1 of 2 treatment groups:
• Group A: Subjects with any solid tumor (including lymphomas).
• 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.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• Life expectancy ≥3 months in the judgment of the investigator.
• Adequate organ function.
• Group A subjects must have measurable or evaluable disease per the appropriate disease criteria.
• 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.
• 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 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).
• Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements.

You may not qualify if:

• Prior exposure to a bromodomain inhibitor, such as OTX-015 or CPI-0610.
• 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.
• Known uncontrolled fungal, bacterial, and/or viral infection ≥Grade 2.
• Uncontrolled autoimmune hemolytic anemia or thrombocytopenia.
• 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.
• 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.
• Women who are pregnant or are 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.
• 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.
• 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.
• Active secondary malignancy
• Major surgery or significant traumatic injury within 14 days prior to therapy
• Receipt of anti-cancer therapy 14 days prior to Cycle 1 Day 1

Sponsors & Collaborators

• Plexxikon: lead

Study Sites (5)

Columbia University Medical Center

New York, New York, 10032, United States

Location

The Ohio State University Stephanie Spielman Comprehensive Breast Center

Columbus, Ohio, 43212, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MUSC/ Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Lymphoma, Non-Hodgkin

Interventions

PLX51107

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

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

Study Record Dates

• First Submitted: February 12, 2016
• First Posted: February 17, 2016
• Study Start: March 1, 2016
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: December 24, 2018

Record last verified: 2018-12

Locations

US (5)