Study to Assess the Safety, Tolerability and Pharmacokinetics of Fimepinostat (CUDC-907) in Patients With Lymphoma
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
1 other identifier
interventional
106
1 country
11
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 lymphoma
Started Dec 2012
Longer than P75 for phase_1 lymphoma
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2012
CompletedFirst Submitted
Initial submission to the registry
December 4, 2012
CompletedFirst Posted
Study publicly available on registry
December 6, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 9, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
October 9, 2020
CompletedMay 6, 2021
May 1, 2021
7.9 years
December 4, 2012
May 5, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
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).
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).
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
ORR assessments as measured using Lugano criteria.
24 months
To evaluate the efficacy of fimepinostat in combination with anti-cancer regimens by evaluating DOR
DOR assessments as measured using Lugano criteria.
24 months
Secondary Outcomes (15)
To assess pharmacokinetics (PK) of fimepinostat when administered in combination with anti-cancer regimens as measured by 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).
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).
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).
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).
Pre-dose to 21 - 28 days post dose
- +10 more secondary outcomes
Study Arms (13)
Fimepinostat - Continuous Once Daily
EXPERIMENTALFimepinostat 30-60 mg/day
Fimepinostat - 2x/week
EXPERIMENTALFimepinostat 60-240 mg/day
Fimepinostat - 3x/week
EXPERIMENTALFimepinostat 60-180 mg/day
Fimepinostat - 4x/week
EXPERIMENTALFimepinosta 60-180 mg/day
Fimepinostat - 5x/week
EXPERIMENTALFimepinostat 60-180 mg/day
Fimepinostat - Expansion 5x/week
EXPERIMENTALFimepinostat 60 mg on the 5 days on/2 days off
Fimepinostat - Expansion 3x/week
EXPERIMENTALFimepinostat 120 mg 3 days on/4 days off
Fimepinostat 60 mg - Combination w/ rituximab
EXPERIMENTALFimepinostat 60 mg 5 days on.2 days off plus rituximab
Fimepinostat 120 mg - Combination w/ rituximab
EXPERIMENTALFimepinostat 120 mg 3x/week plus rituximab
Fimepinostat - Biocomparability Arm
EXPERIMENTALBiocomparability Arm
Fimepinostat 30 mg - Combination w/ venetoclax
EXPERIMENTALFimepinostat 30 mg 5 days on/2 days off plus venetoclax. Different combinations of dose levels for venetoclax will be explored
Fimepinostat 60 mg - Combination w/ venetoclax
EXPERIMENTALFimepinostat 60 mg 5 days on/2 days off plus venetoclax. Different combinations of dose levels for venetoclax will be explored
Fimepinostat - Combination w/ venetoclax and rituximab
EXPERIMENTALFimepinostat 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
Interventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Curis, Inc.lead
- The Leukemia and Lymphoma Societycollaborator
Study Sites (11)
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
Florida Cancer Specialists
Sarasota, Florida, 34232, United States
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322, United States
University of Chicago Medicine
Chicago, Illinois, 60637, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065, United States
Stephenson Cancer Center, University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Swedish Cancer Institute
Seattle, Washington, 98104, United States
Related Publications (2)
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.
PMID: 28860342DERIVEDYounes 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.
PMID: 27049457DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
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
December 4, 2012
First Posted
December 6, 2012
Study Start
December 1, 2012
Primary Completion
October 9, 2020
Study Completion
October 9, 2020
Last Updated
May 6, 2021
Record last verified: 2021-05