Clinical trial NCT02674750: Study to Evaluate the Efficacy and Safety of CUDC-907 in Patients With RR DLBCL, Including Patients With MYC Alterations
Official title: Open-Label, Phase 2 Study to Evaluate the Efficacy and Safety of CUDC-907 in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma, Including Patients With MYC Alterations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Relapsed and/or Refractory Diffuse Large B-cell Lymphoma Including With Myc Alterations
Keywords: DLBCL
MYC
Lead sponsor: Curis, Inc.
Sponsor class: INDUSTRY
First posted: 2016-02-04
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 2, open-label, multicenter trial designed to evaluate the efficacy and safety of CUDC-907 in subjects 18 years and older with Relapsed/Refractory (RR) MYC-altered Diffuse Large B-Cell Lymphoma (DLBCL).

Detailed description: Patients with RR DLBCL will be eligible for treatment with CUDC-907, as long as they have tumor tissue available that can be tested for MYC-altered disease based on one of the following:

* Fresh tumor tissue obtained from biopsy accessible lesions , or
* Archived tumor tissue (most recent available)

Subjects will be required to submit archival tumor samples (most recent available) or fresh tumor samples for central FISH and IHC testing. Subjects whose tumors have been previously characterized as MYC-altered are strongly encouraged to enter the study. For subjects who enter the study with unconfirmed MYC-altered disease, fresh tumor samples are preferred.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years.
2. At least 2 but no more than 4 prior lines of therapy for the treatment of de novo DLBCL and ineligible for (or failed) autologous or allogeneic stem cell transplant (SCT) (salvage therapy, conditioning therapy and maintenance with transplant will be considered one prior treatment). NOTE: For follicular lymphoma transformed to DLBCL (t-FL/DLBCL), single agent non-cytotoxic therapy will not be considered as a line of therapy.
3. Histopathologically confirmed diagnosis of one of the following:

   * RR DLBCL per the 2008 World Health Organization (WHO) classification of hematopoietic and lymphoid tumors (Swerdlow et al, 2008).
   * High grade B-cell lymphoma (HGBL), with MYC and BCL2 and/or BCL6 rearrangements or DLBCL, NOS per the 2016 revision of the WHO classification of lymphoid neoplasms (Swerdlow et al, 2016).
   * Diagnosis of t-FL/DLBCL is allowed. However, other B-cell lymphomas including other transformed indolent lymphomas/DLBCL per the 2008 WHO classification, and Burkitt lymphoma are not eligible.

Exclusion Criteria:

1. Known primary mediastinal, ocular, epidural, testicular or breast DLBCL.
2. Active CNS involvement of their malignancy.
3. Known allergy or hypersensitivity to phosphatidylinositol 3 kinase (PI3K) inhibitors or any component of the formulations used in this study.
4. Cytotoxic anticancer therapy (e.g., alkylating agents, anti-metabolites, purine analogues) or any other systemic anticancer therapy within 2 weeks of study entry.
5. Radiotherapy delivered to non-target lesions within one week prior to starting study treatment or delivered to target lesions that will be followed on the study (note: prior sites of radiation will be recorded).
6. Treatment with experimental therapy within 5 terminal half-lives (t1/2) or 4 weeks prior to enrollment, whichever is longer.
7. Current or planned glucocorticoid therapy, with the following exceptions:

   * Doses ≤ 10 mg/kg/day prednisolone or equivalent is allowed, provided that the steroid dose has been stable or tapering for at least 14 days prior to the first dose of CUDC-907.
   * Inhaled, intranasal, intraarticular, and topical steroids are permitted.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 2 Years
Secondary outcomes:
measure: Median Progression-free Survival
timeFrame: 1 year
measure: Overall Survival (OS)
timeFrame: 1 year
measure: Disease Control Rate (DCR)
timeFrame: 1 year
measure: Number of Participants and Severity of Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety Parameters
timeFrame: AEs were collected for each participant for the duration that they remained on the study, on average of 4 months
Other outcomes:
Locations:
city: Fresno
country: United States
facility: University of California San Francisco-Fresno
state: California
city: Los Angeles
country: United States
facility: University of Southern California, Norris Comprehensive Cancer Center
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center (OUHSC)
state: Oklahoma
city: Tulsa
country: United States
facility: Cancer Care Associates
state: Oklahoma
city: Hershey
country: United States
facility: Penn State Hershey Cancer Institute-Clinical Trials Office
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Knoxville
country: United States
facility: University of Tennessee Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology Sarah Cannon
state: Tennessee
city: Dallas
country: United States
facility: Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: The University of Texas M.D. Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Durán i Reynals, Servicio de Oncología
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
Study officials:
References: