Study to Assess the Safety, Tolerability and Pharmacokinetics of Fimepinostat (CUDC-907) in Patients With Lymphoma

May 5, 2021 updated by: Curis, Inc.

Phase 1 Open Label, Multi-center, Dose-Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Orally Administered Fimepinostat (CUDC-907), a PI3K and HDAC Inhibitor, in Subjects With Refractory or Relapsed Lymphoma

This is a phase 1, open-label, dose-escalation study of fimepinostat (CUDC-907) in patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL), or high-grade B-cell lymphoma (HGBL) with or without MYC and BCL2 alterations. Fimepinostat (CUDC-907) is a multi-targeted agent designed to inhibit phosphoinositide 3-kinase (PI3K)and histone deacetylase (HDAC). The study is designed to assess the safety, the maximum tolerated dose, the recommended phase 2 dose (RP2D), pharmacokinetics and the anti-cancer activity of oral fimepinostat in combination with 1 or more anti-cancer regimens.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
106

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90033
        • USC/Norris Comprehensive Cancer Center
    • Florida
      • Sarasota, Florida, United States, 34232
        • Florida Cancer Specialists
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute, Emory University
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medicine
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Stephenson Cancer Center, University of Oklahoma Health Sciences Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients ≥ 18 years of age with any of the following: Histopathologically confirmed DLBCL or HGBL (i.e., HGBL with MYC, BCL2, and/or BCL6 rearrangements, HGBL, not otherwise specified [NOS], or DLBCL, NOS) that is refractory to, or has relapsed after, treatment with at least 1 prior regimen. Eligible sub-types include DHL, THL, or DEL, as well as DLBCL or HGBL without MYC and/or BCL2 alterations. Criteria for DHL are concurrent MYC translocation+ and BCL2 translocation+ by fluorescence in situ hybridization (FISH) (same criteria for THL, which also includes BCL6 translocation+ by FISH); criteria for DEL are concurrent overexpression of MYC (≥ 40%) and BCL2 (> 50%) by immunohistochemistry (IHC).
  • Measurable disease by CT or PET/CT. MRI acceptable as per protocol.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Recovery to Grade 1 or baseline of any toxicity due to prior systemic treatments (excluding alopecia).
  • Absolute neutrophil count ≥ 1,000/µL; platelets ≥ 75,000/µL for patients with no bone marrow involvement by malignancy; platelets ≥ 50,000/µL for patients with bone marrow involvement by malignancy.
  • Creatinine ≤ 1.5x upper limit of normal (ULN); total bilirubin ≤ 1.5x ULN; AST/ALT ≤ 2.5x ULN.
  • Life expectancy of at least 3 months.

Exclusion Criteria:

  • Intention to undergo stem cell transplant (SCT) or treatment with chimeric antigen receptor (CAR) T-cell therapy.
  • SCT therapy within 100 days prior to starting study treatment.
  • Systemic anti-cancer therapy or investigational agent within 3 weeks of study entry, except for nitrosoureas or mitomycin C (6 weeks).
  • Other non-cytotoxic anti-cancer therapy or investigational agent within 5 half-lives or 21 days prior to study treatment, whichever is shorter, as long as any drug related toxicities have resolved to Grade 1 or less. Dexamethasone up to 12 mg/d is allowed as supportive therapy and does not exclude participation.
  • Contraindication to venetoclax or rituximab.
  • Progressive disease during treatment or within 3 months of stopping prior treatment with a BCL2 inhibitor, histone deacetylase (HDAC) inhibitor, or phosphoinositide-3 kinase (PI3k) inhibitor, or prior discontinuation of any of these therapies due to clinically significant toxicity.
  • Graft vs. host disease following prior allogeneic transplant within 3 months prior to study treatment.
  • Ongoing treatment with chronic immunosuppressants.
  • Active CNS lymphoma.
  • Known gastrointestinal condition that would interfere with swallowing or the oral absorption or tolerance of fimepinostat.
  • Serious infection requiring systemic antibiotic therapy within 14 days prior to study treatment.
  • Uncontrolled or severe cardiovascular disease
  • Unstable or clinically significant concurrent medical condition.
  • Second primary malignancy within 2 years of study entry other than what is specified in the protocol.
  • Known HIV positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection.
  • Active CMV infection, presence of CMV antigenemia, or evidence of any invasive CMV end organ disease (e.g., CMV colitis).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Fimepinostat - Continuous Once Daily
Fimepinostat 30-60 mg/day
Drug: fimepinostat
Other Names:
  • CUDC-907
EXPERIMENTAL: Fimepinostat - 2x/week
Fimepinostat 60-240 mg/day
Drug: fimepinostat
Other Names:
  • CUDC-907
EXPERIMENTAL: Fimepinostat - 3x/week
Fimepinostat 60-180 mg/day
Drug: fimepinostat
Other Names:
  • CUDC-907
EXPERIMENTAL: Fimepinostat - 4x/week
Fimepinosta 60-180 mg/day
Drug: fimepinostat
Other Names:
  • CUDC-907
EXPERIMENTAL: Fimepinostat - 5x/week
Fimepinostat 60-180 mg/day
Drug: fimepinostat
Other Names:
  • CUDC-907
EXPERIMENTAL: Fimepinostat - Expansion 5x/week
Fimepinostat 60 mg on the 5 days on/2 days off
Drug: fimepinostat
Other Names:
  • CUDC-907
EXPERIMENTAL: Fimepinostat - Expansion 3x/week
Fimepinostat 120 mg 3 days on/4 days off
Drug: fimepinostat
Other Names:
  • CUDC-907
EXPERIMENTAL: Fimepinostat 60 mg - Combination w/ rituximab
Fimepinostat 60 mg 5 days on.2 days off plus rituximab
Drug: Rituximab
Drug: fimepinostat
Other Names:
  • CUDC-907
EXPERIMENTAL: Fimepinostat 120 mg - Combination w/ rituximab
Fimepinostat 120 mg 3x/week plus rituximab
Drug: Rituximab
Drug: fimepinostat
Other Names:
  • CUDC-907
EXPERIMENTAL: Fimepinostat - Biocomparability Arm
Biocomparability Arm
Drug: fimepinostat
Other Names:
  • CUDC-907
EXPERIMENTAL: Fimepinostat 30 mg - Combination w/ venetoclax
Fimepinostat 30 mg 5 days on/2 days off plus venetoclax. Different combinations of dose levels for venetoclax will be explored
Drug: venetoclax
Drug: fimepinostat
Other Names:
  • CUDC-907
EXPERIMENTAL: Fimepinostat 60 mg - Combination w/ venetoclax
Fimepinostat 60 mg 5 days on/2 days off plus venetoclax. Different combinations of dose levels for venetoclax will be explored
Drug: venetoclax
Drug: fimepinostat
Other Names:
  • CUDC-907
EXPERIMENTAL: Fimepinostat - Combination w/ venetoclax and rituximab
Fimepinostat and venetoclax dosed at dose levels determined for that combination. Rituximab dosed at 375 mg/m2 IV on Day 1 of each 21 day cycle
Drug: Rituximab
Drug: fimepinostat
Other Names:
  • CUDC-907

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of oral fimepinostat (CUDC-907) in combination with venetoclax and rituximab
Time Frame: At the end of cycle 1 or 2 (each cycle is 21 days)
To be evaluated in patients with relapsed and/or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL). Within any given study arm, the highest dose level studied at which fewer than 2 out of 6 subjects (< 33%) experience a dose limiting toxicity (DLT).
At the end of cycle 1 or 2 (each cycle is 21 days)
To assess the safety and tolerability of fimepinostat in combination with anti-cancer regimens by evaluating the number of participants with adverse events assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE, v4.0).
Time Frame: 18 months
Number of participants with adverse events assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE, v4.0).
18 months
To evaluate the efficacy of fimepinostat in combination with anti-cancer regimens by evaluating ORR
Time Frame: 24 months
ORR assessments as measured using Lugano criteria.
24 months
To evaluate the efficacy of fimepinostat in combination with anti-cancer regimens by evaluating DOR
Time Frame: 24 months
DOR assessments as measured using Lugano criteria.
24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To assess pharmacokinetics (PK) of fimepinostat when administered in combination with anti-cancer regimens as measured by area under the concentration-time curve (AUC).
Time Frame: Pre-dose to 21 - 28 days post dose
Pharmacokinetic parameters will include area under the concentration-time curve (AUC).
Pre-dose to 21 - 28 days post dose
To assess pharmacokinetics (PK) of fimepinostat when administered in combination with anti-cancer regimens as measured by maximum plasma concentration (Cmax).
Time Frame: Pre-dose to 21 - 28 days post dose
Pharmacokinetic parameters will include maximum plasma concentration (Cmax).
Pre-dose to 21 - 28 days post dose
To assess pharmacokinetics (PK) of fimepinostat when administered in combination with anti-cancer regimens as measured by half-life (T1/2).
Time Frame: Pre-dose to 21 - 28 days post dose
Pharmacokinetic parameters will include half-life (T1/2).
Pre-dose to 21 - 28 days post dose
To assess pharmacokinetics (PK) of fimepinostat when administered in combination with anti-cancer regimens as measured by clearance (Cl).
Time Frame: Pre-dose to 21 - 28 days post dose
Pharmacokinetic parameters will include clearance (Cl).
Pre-dose to 21 - 28 days post dose
To assess pharmacokinetics (PK) of fimepinostat when administered in combination with anti-cancer regimens as measured by volume of distribution (Vd).
Time Frame: Pre-dose to 21 - 28 days post dose
Pharmacokinetic parameters will include volume of distribution (Vd).
Pre-dose to 21 - 28 days post dose
To assess PK of venetoclax when administered in combination with fimepinostat as measured by area under the concentration-time curve (AUC).
Time Frame: Pre-dose to 21 - 28 days post dose
Pharmacokinetic parameters will include area under the concentration-time curve (AUC).
Pre-dose to 21 - 28 days post dose
To assess PK of venetoclax when administered in combination with fimepinostat as measured by maximum plasma concentration (Cmax).
Time Frame: Pre-dose to 21 - 28 days post dose
Pharmacokinetic parameters will include maximum plasma concentration (Cmax).
Pre-dose to 21 - 28 days post dose
To assess PK of venetoclax when administered in combination with fimepinostat as measured by half-life (T1/2).
Time Frame: Pre-dose to 21 - 28 days post dose
Pharmacokinetic parameters will include half-life (T1/2).
Pre-dose to 21 - 28 days post dose
To assess PK of venetoclax when administered in combination with fimepinostat as measured by clearance (Cl).
Time Frame: Pre-dose to 21 - 28 days post dose
Pharmacokinetic parameters will include clearance (Cl).
Pre-dose to 21 - 28 days post dose
To assess PK of venetoclax when administered in combination with fimepinostat as measured by volume of distribution (Vd).
Time Frame: Pre-dose to 21 - 28 days post dose
Pharmacokinetic parameters will include volume of distribution (Vd).
Pre-dose to 21 - 28 days post dose
To evaluate the efficacy of fimepinostat in combination with anti-cancer regimens as measured by OS.
Time Frame: 24 months
OS measured using RECIL 2017 criteria and revised RECIST 1.1.
24 months
To evaluate the efficacy of fimepinostat in combination with anti-cancer regimens as measured by PFS.
Time Frame: 24 months
PFS measured using RECIL 2017 criteria and revised RECIST 1.1.
24 months
To evaluate the efficacy of fimepinostat in combination with anti-cancer regimens as measured by ORR.
Time Frame: 24 months
ORR measured using RECIL 2017 criteria and revised RECIST 1.1.
24 months
To evaluate the efficacy of fimepinostat in combination with anti-cancer regimens as measured by DOR.
Time Frame: 24 months
DOR measured using RECIL 2017 criteria and revised RECIST 1.1.
24 months
To evaluate biomarkers of fimepinostat activity
Time Frame: 24 months
Exploratory biological markers of fimepinostat activity will be assessed in PBMCs, plasma, and tumor and samples to explore biomarkers that correlate with safety and/or efficacy, such as CREBBP/EP300.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Curis, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
The Leukemia and Lymphoma Society

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2012

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 9, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 9, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 4, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 4, 2012

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 6, 2012

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 6, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 5, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CUDC-907-101

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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