Study to Assess the Safety, Tolerability and Pharmacokinetics of Fimepinostat (CUDC-907) in Patients With Lymphoma
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ClinicalTrials.gov Identifier: NCT01742988 |
Recruitment Status :
Completed
First Posted : December 6, 2012
Last Update Posted : May 6, 2021
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Condition or disease | Intervention/treatment | Phase |
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Lymphoma Relapsed Lymphoma Refractory Lymphoma Relapsed and/or Refractory Lymphoma Relapsed Ddiffuse Large B-Cell Lymphoma (DLBCL) Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Relapsed and/or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Double-hit Lymphoma (DHL) Triple-hit Lymphoma (THL) Double-expressor Lymphoma (DEL) High-grade B-cell Lymphoma (HGBL) | Drug: fimepinostat Drug: Rituximab Drug: venetoclax | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 106 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Study Start Date : | December 2012 |
Actual Primary Completion Date : | October 9, 2020 |
Actual Study Completion Date : | October 9, 2020 |

Arm | Intervention/treatment |
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Experimental: Fimepinostat - Continuous Once Daily
Fimepinostat 30-60 mg/day
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Drug: fimepinostat
Other Name: CUDC-907 |
Experimental: Fimepinostat - 2x/week
Fimepinostat 60-240 mg/day
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Drug: fimepinostat
Other Name: CUDC-907 |
Experimental: Fimepinostat - 3x/week
Fimepinostat 60-180 mg/day
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Drug: fimepinostat
Other Name: CUDC-907 |
Experimental: Fimepinostat - 4x/week
Fimepinosta 60-180 mg/day
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Drug: fimepinostat
Other Name: CUDC-907 |
Experimental: Fimepinostat - 5x/week
Fimepinostat 60-180 mg/day
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Drug: fimepinostat
Other Name: CUDC-907 |
Experimental: Fimepinostat - Expansion 5x/week
Fimepinostat 60 mg on the 5 days on/2 days off
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Drug: fimepinostat
Other Name: CUDC-907 |
Experimental: Fimepinostat - Expansion 3x/week
Fimepinostat 120 mg 3 days on/4 days off
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Drug: fimepinostat
Other Name: CUDC-907 |
Experimental: Fimepinostat 60 mg - Combination w/ rituximab
Fimepinostat 60 mg 5 days on.2 days off plus rituximab
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Drug: fimepinostat
Other Name: CUDC-907 Drug: Rituximab |
Experimental: Fimepinostat 120 mg - Combination w/ rituximab
Fimepinostat 120 mg 3x/week plus rituximab
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Drug: fimepinostat
Other Name: CUDC-907 Drug: Rituximab |
Experimental: Fimepinostat - Biocomparability Arm
Biocomparability Arm
|
Drug: fimepinostat
Other Name: 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: fimepinostat
Other Name: CUDC-907 Drug: venetoclax |
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: fimepinostat
Other Name: CUDC-907 Drug: venetoclax |
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: fimepinostat
Other Name: CUDC-907 Drug: Rituximab |
- 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).
- 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).
- 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.
- 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.
- 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).
- 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).
- 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).
- 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).
- 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).
- 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).
- 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).
- 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).
- 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).
- 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).
- 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.
- 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.
- 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.
- 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.
- 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.

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

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): NCT01742988
United States, California | |
USC/Norris Comprehensive Cancer Center | |
Los Angeles, California, United States, 90033 | |
United States, Florida | |
Florida Cancer Specialists | |
Sarasota, Florida, United States, 34232 | |
United States, Georgia | |
Winship Cancer Institute, Emory University | |
Atlanta, Georgia, United States, 30322 | |
United States, Illinois | |
University of Chicago Medicine | |
Chicago, Illinois, United States, 60637 | |
United States, Michigan | |
University of Michigan | |
Ann Arbor, Michigan, United States, 48109 | |
United States, New York | |
Memorial Sloan-Kettering Cancer Center | |
New York, New York, United States, 10065 | |
United States, Oklahoma | |
Stephenson Cancer Center, University of Oklahoma Health Sciences Center | |
Oklahoma City, Oklahoma, United States, 73104 | |
United States, Pennsylvania | |
Hospital of the University of Pennsylvania | |
Philadelphia, Pennsylvania, United States, 19104 | |
United States, Tennessee | |
Sarah Cannon Research Institute | |
Nashville, Tennessee, United States, 37203 | |
United States, Texas | |
MD Anderson Cancer Center | |
Houston, Texas, United States, 77030 | |
United States, Washington | |
Swedish Cancer Institute | |
Seattle, Washington, United States, 98104 |
Responsible Party: | Curis, Inc. |
ClinicalTrials.gov Identifier: | NCT01742988 |
Other Study ID Numbers: |
CUDC-907-101 |
First Posted: | December 6, 2012 Key Record Dates |
Last Update Posted: | May 6, 2021 |
Last Verified: | May 2021 |
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 |
Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |
Lymphoma, Non-Hodgkin Rituximab Venetoclax Antineoplastic Agents, Immunological Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents |