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

Status: Active

Description

This is a phase 1 / 2, open-label, dose-escalation study of fimepinostat (CUDC-907) in patients with relapsed and / or refractory lymphoma, 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.

Eligibility Criteria

Inclusion Criteria

  • Inclusion Criteria: Subjects of ≥ 18 years of age with any of the following: For Dose-Escalation cohorts: - Fimepinostat + venetoclax: Histopathologically confirmed DLBCL or HGBL that is refractory to, or has relapsed after, treatment with at least 1 prior regimen - Fimepinostat + rituximab + bendamustine: Histopathologically confirmed diagnosis of lymphoma (i.e., B-cell non-Hodgkin lymphoma [NHL], TCL, or HL) that is refractory to, or has relapsed after, treatment with at least 1 prior regimen. For Dose-Expansion cohorts: - Fimepinostat + venetoclax: R/R DLBCL or HGBL with both MYC and BCL2 alterations and/or overexpression (DHL, THL, or DEL) that is refractory to, or has relapsed after, 1 or more prior lines of therapy. - Fimepinostat + rituximab + bendamustine: R/R DLBCL or HGBL that is refractory to, or has relapsed after, 1 or more prior lines of therapy - 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 or treatment with chimeric antigen receptor (CAR) T-cell therapy. - 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. - 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).

Locations & Contacts

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: In review
Contact: April Johnson
Phone: 949-653-2959ext118
Email: AprilDJohnson@mednet.ucla.edu

Georgia

Atlanta
Emory Saint Joseph's Hospital
Status: Active
Name Not Available
Emory University Hospital / Winship Cancer Institute
Status: Active
Name Not Available
Emory University Hospital Midtown
Status: Active
Name Not Available

Michigan

Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: Active
Name Not Available

Pennsylvania

Philadelphia
University of Pennsylvania / Abramson Cancer Center
Status: Active
Name Not Available

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Curis

Trial IDs

Primary ID CUDC-907-101
Secondary IDs NCI-2014-00764
Clinicaltrials.gov ID NCT01742988