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

Phase 2

Completed

Conditions: Relapsed and/or Refractory Diffuse Large B-cell Lymphoma Including With Myc Alterations

Interventions: Drug: CUDC-907

Registration Number: NCT02674750

Lead Sponsor: Curis, Inc.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 70

Inclusion Criteria

Age ≥ 18 years.
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.
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

Known primary mediastinal, ocular, epidural, testicular or breast DLBCL.
Active CNS involvement of their malignancy.
Known allergy or hypersensitivity to phosphatidylinositol 3 kinase (PI3K) inhibitors or any component of the formulations used in this study.
Cytotoxic anticancer therapy (e.g., alkylating agents, anti-metabolites, purine analogues) or any other systemic anticancer therapy within 2 weeks of study entry.
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).
Treatment with experimental therapy within 5 terminal half-lives (t1/2) or 4 weeks prior to enrollment, whichever is longer.
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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Median Progression-free Survival	1 year	Efficacy of CUDC-907 in subjects with Relapsed/Refractory MYC-altered DLBCL
Overall Survival (OS)	1 year	Efficacy of CUDC-907 in subjects with Relapsed/Refractory MYC-altered DLBCL
Disease Control Rate (DCR)	1 year	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.
Number of Participants and Severity of Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety Parameters	AEs were collected for each participant for the duration that they remained on the study, on average of 4 months	Number of participants and severity of adverse events (AEs), serious adverse events (SAEs), and other safety parameters in patients receiving CUDC-907.

Trial Locations

Locations (25): Charles A. Sammons Cancer Center
🇺🇸
Dallas, Texas, United States
Karmanos Cancer Institute
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Detroit, Michigan, United States
Swedish Cancer Institute
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Seattle, Washington, United States
University of Chicago
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Chicago, Illinois, United States
The University of Texas M.D. Anderson Cancer Center
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Houston, Texas, United States
Hospital of the University of Pennsylvania
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Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
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Philadelphia, Pennsylvania, United States
Tennessee Oncology Sarah Cannon
🇺🇸
Nashville, Tennessee, United States
Houston Methodist Hospital
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Houston, Texas, United States
Moffitt Cancer Center
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Tampa, Florida, United States
University of Oklahoma Health Sciences Center (OUHSC)
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Oklahoma City, Oklahoma, United States
University of Rochester
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Rochester, New York, United States
Hospital Durán i Reynals, Servicio de Oncología
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Barcelona, Spain
University of California San Francisco-Fresno
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Fresno, California, United States
University of Southern California, Norris Comprehensive Cancer Center
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Los Angeles, California, United States
Winship Cancer Institute of Emory University
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Atlanta, Georgia, United States
Mayo Clinic
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Rochester, Minnesota, United States
Penn State Hershey Cancer Institute-Clinical Trials Office
🇺🇸
Hershey, Pennsylvania, United States
Hospital Universitari Vall d'Hebron
🇪🇸
Barcelona, Spain
Hospital Universitario Puerta de Hierro
🇪🇸
Madrid, Spain
Hospital de la Santa Creu i Sant Pau
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Barcelona, Spain
Hospital Universitario de Salamanca
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Salamanca, Spain
Norton Cancer Institute
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Louisville, Kentucky, United States
Cancer Care Associates
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Tulsa, Oklahoma, United States
University of Tennessee Cancer Center
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Knoxville, Tennessee, United States