Study to Evaluate the Efficacy and Safety of CUDC-907 in Patients With RR DLBCL, Including Patients With MYC Alterations

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

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).

Study Overview

• Status: Completed
• Conditions: Relapsed and/or Refractory Diffuse Large B-cell Lymphoma Including With Myc Alterations
• Intervention / Treatment: Drug: CUDC-907

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.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08041
    • Hospital de La Santa Creu i Sant Pau
  • Barcelona, Spain, 08908
    • Hospital Durán i Reynals, Servicio de Oncología
  • Madrid, Spain, 28220
    • Hospital Universitario Puerta de Hierro
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
• United States
  • California
    • Fresno, California, United States, 93701
      • University of California San Francisco-Fresno
    • Los Angeles, California, United States, 90033
      • University of Southern California, Norris Comprehensive Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
  • Illinois
    • Chicago, Illinois, United States, 60647
      • University of Chicago
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • Rochester, New York, United States, 55905
      • University of Rochester
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center (OUHSC)
    • Tulsa, Oklahoma, United States, 74104
      • Cancer Care Associates
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Cancer Institute-Clinical Trials Office
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Cancer Center
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology Sarah Cannon
  • Texas
    • Dallas, Texas, United States, 75246
      • Charles A. Sammons Cancer Center
    • Houston, Texas, United States, 77030
      • The University of Texas M.D. Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group A; Group A: MYC translocation+ and/or MYC gene copy number gain by FISH	Drug: CUDC-907
EXPERIMENTAL: Group B; Group B: MYC expression in > 40% of tumor cells by IHC	Drug: CUDC-907
EXPERIMENTAL: Group C; Group C: MYC translocation- by FISH, and MYC expression in < 40% of tumor cells, and no MYC gene copy number gain by FISH	Drug: CUDC-907

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Efficacy of CUDC-907 in subjects with Relapsed/Refractory MYC-altered Diffuse Large B-Cell Lymphoma (DLBCL)	2 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Progression-free Survival	Efficacy of CUDC-907 in subjects with Relapsed/Refractory MYC-altered DLBCL	1 year
Overall Survival (OS)	Efficacy of CUDC-907 in subjects with Relapsed/Refractory MYC-altered DLBCL	1 year
Disease Control Rate (DCR)	Efficacy of CUDC-907 in subjects with Relapsed/Refractory MYC-altered DLBCL Note: Response is defined using Cheson 2007 criteria. CR=Complete Response; PR=Partial Response; SD=Stable Disease. a. Two-sided exact binomial 95% confidence interval. Revised Response Criteria for Malignant Lymphoma (Cheson 2007) was used for the assessment of response. DCR is defined as the proportion of patients having best response of complete response, partial response, or stable disease.	1 year
Number of Participants and Severity of Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety Parameters	Number of participants and severity of adverse events (AEs), serious adverse events (SAEs), and other safety parameters in patients receiving CUDC-907.	AEs were collected for each participant for the duration that they remained on the study, on average of 4 months

Collaborators and Investigators

• Sponsor: Curis, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (ACTUAL): May 28, 2019
• Study Completion (ACTUAL): May 28, 2019

Study Registration Dates

• First Submitted: January 29, 2016
• First Submitted That Met QC Criteria: February 3, 2016
• First Posted (ESTIMATE): February 4, 2016

Study Record Updates

• Last Update Posted (ACTUAL): April 27, 2022
• Last Update Submitted That Met QC Criteria: April 25, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: DLBCL; MYC
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: CUDC-907-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED