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LymphomaPhase 1NCT01742988

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

A Phase 1 study testing fimepinostat, Rituximab and venetoclax in people with Lymphoma and Relapsed Lymphoma, run by Curis, Inc. at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, Relapsed Lymphoma, Refractory Lymphoma
What is being tested?
fimepinostat, Rituximab and venetoclax
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
106 participants
Where
11 sitesUnited States
Study dates
Dec 2012to 9 Oct 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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).

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Winship Cancer Institute, Emory University

    Atlanta, Georgia, 30322

  • University of Chicago Medicine

    Chicago, Illinois, 60637

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • USC/Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Stephenson Cancer Center, University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Florida Cancer Specialists

    Sarasota, Florida, 34232

  • Swedish Cancer Institute

    Seattle, Washington, 98104

Other trials in United States

About this study

Official title: 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.

Being tested
fimepinostat, Rituximab, venetoclax
Keywords
Lymphoma, DLBCL, MYC, Diffuse Large B-Cell Lymphoma, HGBL, High-grade B-Cell Lymphoma, Double-hit Lymphoma (DHL), Triple-hit Lymphoma (THL), Double-expressor Lymphoma (DEL), P13K, HDAC, Open-Label
Medical subject headings
Lymphoma, Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01742988
Study groupRoleWhat they receive
Fimepinostat - Continuous Once DailyExperimentalFimepinostat 30-60 mg/day
Receives: Drug: fimepinostat
Fimepinostat - 2x/weekExperimentalFimepinostat 60-240 mg/day
Receives: Drug: fimepinostat
Fimepinostat - 3x/weekExperimentalFimepinostat 60-180 mg/day
Receives: Drug: fimepinostat
Fimepinostat - 4x/weekExperimentalFimepinosta 60-180 mg/day
Receives: Drug: fimepinostat
Fimepinostat - 5x/weekExperimentalFimepinostat 60-180 mg/day
Receives: Drug: fimepinostat
Fimepinostat - Expansion 5x/weekExperimentalFimepinostat 60 mg on the 5 days on/2 days off
Receives: Drug: fimepinostat
Fimepinostat - Expansion 3x/weekExperimentalFimepinostat 120 mg 3 days on/4 days off
Receives: Drug: fimepinostat
Fimepinostat 60 mg - Combination w/ rituximabExperimentalFimepinostat 60 mg 5 days on.2 days off plus rituximab
Receives: Drug: fimepinostat; Drug: Rituximab
Fimepinostat 120 mg - Combination w/ rituximabExperimentalFimepinostat 120 mg 3x/week plus rituximab
Receives: Drug: fimepinostat; Drug: Rituximab
Fimepinostat - Biocomparability ArmExperimentalBiocomparability Arm
Receives: Drug: fimepinostat
Fimepinostat 30 mg - Combination w/ venetoclaxExperimentalFimepinostat 30 mg 5 days on/2 days off plus venetoclax. Different combinations of dose levels for venetoclax will be explored
Receives: Drug: fimepinostat; Drug: venetoclax
Fimepinostat 60 mg - Combination w/ venetoclaxExperimentalFimepinostat 60 mg 5 days on/2 days off plus venetoclax. Different combinations of dose levels for venetoclax will be explored
Receives: Drug: fimepinostat; Drug: venetoclax
Fimepinostat - Combination w/ venetoclax and rituximabExperimentalFimepinostat 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
Receives: Drug: fimepinostat; Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of oral fimepinostat (CUDC-907) in combination with venetoclax and rituximab

    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).

    Measured: At the end of cycle 1 or 2 (each cycle is 21 days)

  2. 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).

    Number of participants with adverse events assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE, v4.0).

    Measured: 18 months

  3. To evaluate the efficacy of fimepinostat in combination with anti-cancer regimens by evaluating ORR

    ORR assessments as measured using Lugano criteria.

    Measured: 24 months

  4. To evaluate the efficacy of fimepinostat in combination with anti-cancer regimens by evaluating DOR

    DOR assessments as measured using Lugano criteria.

    Measured: 24 months

Secondary outcomes (15)

  1. To assess pharmacokinetics (PK) of fimepinostat when administered in combination with anti-cancer regimens as measured by area under the concentration-time curve (AUC).

    Pharmacokinetic parameters will include area under the concentration-time curve (AUC).

    Measured: Pre-dose to 21 - 28 days post dose

  2. To assess pharmacokinetics (PK) of fimepinostat when administered in combination with anti-cancer regimens as measured by maximum plasma concentration (Cmax).

    Pharmacokinetic parameters will include maximum plasma concentration (Cmax).

    Measured: Pre-dose to 21 - 28 days post dose

  3. To assess pharmacokinetics (PK) of fimepinostat when administered in combination with anti-cancer regimens as measured by half-life (T1/2).

    Pharmacokinetic parameters will include half-life (T1/2).

    Measured: Pre-dose to 21 - 28 days post dose

  4. To assess pharmacokinetics (PK) of fimepinostat when administered in combination with anti-cancer regimens as measured by clearance (Cl).

    Pharmacokinetic parameters will include clearance (Cl).

    Measured: Pre-dose to 21 - 28 days post dose

  5. To assess pharmacokinetics (PK) of fimepinostat when administered in combination with anti-cancer regimens as measured by volume of distribution (Vd).

    Pharmacokinetic parameters will include volume of distribution (Vd).

    Measured: Pre-dose to 21 - 28 days post dose

  6. To assess PK of venetoclax when administered in combination with fimepinostat as measured by area under the concentration-time curve (AUC).

    Pharmacokinetic parameters will include area under the concentration-time curve (AUC).

    Measured: Pre-dose to 21 - 28 days post dose

  7. To assess PK of venetoclax when administered in combination with fimepinostat as measured by maximum plasma concentration (Cmax).

    Pharmacokinetic parameters will include maximum plasma concentration (Cmax).

    Measured: Pre-dose to 21 - 28 days post dose

  8. To assess PK of venetoclax when administered in combination with fimepinostat as measured by half-life (T1/2).

    Pharmacokinetic parameters will include half-life (T1/2).

    Measured: Pre-dose to 21 - 28 days post dose

  9. To assess PK of venetoclax when administered in combination with fimepinostat as measured by clearance (Cl).

    Pharmacokinetic parameters will include clearance (Cl).

    Measured: Pre-dose to 21 - 28 days post dose

  10. To assess PK of venetoclax when administered in combination with fimepinostat as measured by volume of distribution (Vd).

    Pharmacokinetic parameters will include volume of distribution (Vd).

    Measured: Pre-dose to 21 - 28 days post dose

  11. To evaluate the efficacy of fimepinostat in combination with anti-cancer regimens as measured by OS.

    OS measured using RECIL 2017 criteria and revised RECIST 1.1.

    Measured: 24 months

  12. To evaluate the efficacy of fimepinostat in combination with anti-cancer regimens as measured by PFS.

    PFS measured using RECIL 2017 criteria and revised RECIST 1.1.

    Measured: 24 months

  13. To evaluate the efficacy of fimepinostat in combination with anti-cancer regimens as measured by ORR.

    ORR measured using RECIL 2017 criteria and revised RECIST 1.1.

    Measured: 24 months

  14. To evaluate the efficacy of fimepinostat in combination with anti-cancer regimens as measured by DOR.

    DOR measured using RECIL 2017 criteria and revised RECIST 1.1.

    Measured: 24 months

  15. To evaluate biomarkers of fimepinostat activity

    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.

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Dec 2012 (estimated)
  2. Study startDec 2012
  3. Primary completion9 Oct 2020
  4. Study completion9 Oct 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
106 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01742988
Sponsor's protocol ID
CUDC-907-101
Status last verified
May 2021
First submitted
4 Dec 2012
Last updated
6 May 2021
Results posted
No
Data monitoring committee
No

Publications

  • Oki Y, Kelly KR, Flinn I, Patel MR, Gharavi R, Ma A, Parker J, Hafeez A, Tuck D, Younes A. CUDC-907 in relapsed/refractory diffuse large B-cell lymphoma, including patients with MYC-alterations: results from an expanded phase I trial. Haematologica. 2017 Nov;102(11):1923-1930. doi: 10.3324/haematol.2017.172882. Epub 2017 Aug 31.

    PubMed 28860342

  • Younes A, Berdeja JG, Patel MR, Flinn I, Gerecitano JF, Neelapu SS, Kelly KR, Copeland AR, Akins A, Clancy MS, Gong L, Wang J, Ma A, Viner JL, Oki Y. Safety, tolerability, and preliminary activity of CUDC-907, a first-in-class, oral, dual inhibitor of HDAC and PI3K, in patients with relapsed or refractory lymphoma or multiple myeloma: an open-label, dose-escalation, phase 1 trial. Lancet Oncol. 2016 May;17(5):622-31. doi: 10.1016/S1470-2045(15)00584-7. Epub 2016 Mar 31.

    PubMed 27049457

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing fimepinostat, Rituximab and venetoclax in people with Lymphoma and Relapsed Lymphoma, run by Curis, Inc. at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01742988, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2021.

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