Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
estimated completion

Description

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.

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

Keywords

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) DLBCL MYC Diffuse Large B-Cell Lymphoma HGBL High-grade B-Cell Lymphoma P13K HDAC Open-Label Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Rituximab Venetoclax fimepinostat Fimepinostat - Continuous Once Daily Fimepinostat - 2x/week Fimepinostat - 3x/week Fimepinostat - 4x/week Fimepinostat - 5x/week Fimepinostat - Expansion 5x/week Fimepinostat - Expansion 3x/week

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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 CAN'T join 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.
  • Active CMV infection, presence of CMV antigenemia, or evidence of any invasive CMV end organ disease (e.g., CMV colitis).

Locations

  • USC/Norris Comprehensive Cancer Center
    Los Angeles California 90033 United States
  • Swedish Cancer Institute
    Seattle Washington 98104 United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Curis, Inc.
ID
NCT01742988
Phase
Phase 1
Study Type
Interventional
Last Updated