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

NCT ID: NCT01742988

Last Updated: 2021-05-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

106 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-12-31

Study Completion Date

2020-10-09

Brief Summary

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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.

Detailed Description

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Conditions

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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)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Fimepinostat - Continuous Once Daily

Fimepinostat 30-60 mg/day

Group Type EXPERIMENTAL

fimepinostat

Intervention Type DRUG

Fimepinostat - 2x/week

Fimepinostat 60-240 mg/day

Group Type EXPERIMENTAL

fimepinostat

Intervention Type DRUG

Fimepinostat - 3x/week

Fimepinostat 60-180 mg/day

Group Type EXPERIMENTAL

fimepinostat

Intervention Type DRUG

Fimepinostat - 4x/week

Fimepinosta 60-180 mg/day

Group Type EXPERIMENTAL

fimepinostat

Intervention Type DRUG

Fimepinostat - 5x/week

Fimepinostat 60-180 mg/day

Group Type EXPERIMENTAL

fimepinostat

Intervention Type DRUG

Fimepinostat - Expansion 5x/week

Fimepinostat 60 mg on the 5 days on/2 days off

Group Type EXPERIMENTAL

fimepinostat

Intervention Type DRUG

Fimepinostat - Expansion 3x/week

Fimepinostat 120 mg 3 days on/4 days off

Group Type EXPERIMENTAL

fimepinostat

Intervention Type DRUG

Fimepinostat 60 mg - Combination w/ rituximab

Fimepinostat 60 mg 5 days on.2 days off plus rituximab

Group Type EXPERIMENTAL

fimepinostat

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Fimepinostat 120 mg - Combination w/ rituximab

Fimepinostat 120 mg 3x/week plus rituximab

Group Type EXPERIMENTAL

fimepinostat

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Fimepinostat - Biocomparability Arm

Biocomparability Arm

Group Type EXPERIMENTAL

fimepinostat

Intervention Type DRUG

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

Group Type EXPERIMENTAL

fimepinostat

Intervention Type DRUG

venetoclax

Intervention Type DRUG

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

Group Type EXPERIMENTAL

fimepinostat

Intervention Type DRUG

venetoclax

Intervention Type DRUG

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

Group Type EXPERIMENTAL

fimepinostat

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Interventions

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fimepinostat

Intervention Type DRUG

Rituximab

Intervention Type DRUG

venetoclax

Intervention Type DRUG

Other Intervention Names

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CUDC-907

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Leukemia and Lymphoma Society

OTHER

Sponsor Role collaborator

Curis, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Florida Cancer Specialists

Sarasota, Florida, United States

Site Status

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States

Site Status

University of Chicago Medicine

Chicago, Illinois, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Stephenson Cancer Center, University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Swedish Cancer Institute

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 28860342 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27049457 (View on PubMed)

Other Identifiers

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CUDC-907-101

Identifier Type: -

Identifier Source: org_study_id

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