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

• Sponsor: Curis, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02674750
• Collaborator: (none)
• Enrollment: 70
• Locations: 25
• Arms: 3
• Duration (Months): 34.9
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Relapsed and/or Refractory Diffuse Large B-cell Lymphoma Including With Myc Alterations	Drug: CUDC-907	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Jul 1, 2016
• Actual Primary Completion Date: May 28, 2019
• Actual Study Completion Date: May 28, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. Median Progression-free Survival [1 year]

   Efficacy of CUDC-907 in subjects with Relapsed/Refractory MYC-altered DLBCL

2. Overall Survival (OS) [1 year]

   Efficacy of CUDC-907 in subjects with Relapsed/Refractory MYC-altered DLBCL

3. 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.

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Francisco-Fresno	Fresno	California	United States	93701
2	University of Southern California, Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
3	Moffitt Cancer Center	Tampa	Florida	United States	33612
4	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
5	University of Chicago	Chicago	Illinois	United States	60647
6	Norton Cancer Institute	Louisville	Kentucky	United States	40207
7	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
8	Mayo Clinic	Rochester	Minnesota	United States	55905
9	University of Rochester	Rochester	New York	United States	55905
10	University of Oklahoma Health Sciences Center (OUHSC)	Oklahoma City	Oklahoma	United States	73104
11	Cancer Care Associates	Tulsa	Oklahoma	United States	74104
12	Penn State Hershey Cancer Institute-Clinical Trials Office	Hershey	Pennsylvania	United States	17033
13	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
14	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
15	University of Tennessee Cancer Center	Knoxville	Tennessee	United States	37920
16	Tennessee Oncology Sarah Cannon	Nashville	Tennessee	United States	37203
17	Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
18	Houston Methodist Hospital	Houston	Texas	United States	77030
19	The University of Texas M.D. Anderson Cancer Center	Houston	Texas	United States	77030
20	Swedish Cancer Institute	Seattle	Washington	United States	98104
21	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
22	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08041
23	Hospital Durán i Reynals, Servicio de Oncología	Barcelona		Spain	08908
24	Hospital Universitario Puerta de Hierro	Madrid		Spain	28220
25	Hospital Universitario de Salamanca	Salamanca		Spain	37007

Sponsors and Collaborators

• Curis, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 30, 2016
• Informed Consent Form - Feb 2, 2017

More Information

Publications

None provided.

• Responsible Party: Curis, Inc.
• ClinicalTrials.gov Identifier: NCT02674750
• Other Study ID Numbers: CUDC-907-201
• First Posted: Feb 4, 2016
• Last Update Posted: Apr 27, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Curis, Inc.: DLBCL; MYC
• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse

Study Results

Participant Flow

Recruitment Details	Adverse Events were collected from signing of the ICF through the last patient visit. (July2016 - May 2019)

Arm/Group Title	Group A	Group B	Group C
Arm/Group Description	MYC translocation+ and/or MYC gene copy number gain by FISH	MYC expression in > 40% of tumor cells by IHC	MYC translocation- by FISH, and MYC expression in < 40% of tumor cells, and no MYC gene copy number gain by FISH
Period Title: Overall Study
STARTED	5	49	16
COMPLETED	0	4	4
NOT COMPLETED	5	45	12

Baseline Characteristics

Arm/Group Title	Group A	Group B	Group C	Total
Arm/Group Description	MYC translocation+ and/or MYC gene copy number gain by FISH	MYC expression in > 40% of tumor cells by IHC	MYC translocation- by FISH, and MYC expression in < 40% of tumor cells, and no MYC gene copy number gain by FISH	Total of all reporting groups
Overall Participants	5	49	16	70
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 60%	29 59.2%	8 50%	40 57.1%
>=65 years	2 40%	20 40.8%	8 50%	30 42.9%
Sex: Female, Male (Count of Participants)
Female	2 40%	20 40.8%	7 43.8%	29 41.4%
Male	3 60%	29 59.2%	9 56.3%	41 58.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 20%	4 8.2%	1 6.3%	6 8.6%
Not Hispanic or Latino	3 60%	44 89.8%	14 87.5%	61 87.1%
Unknown or Not Reported	1 20%	1 2%	1 6.3%	3 4.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	1 6.3%	1 1.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	3 6.1%	0 0%	3 4.3%
White	4 80%	44 89.8%	14 87.5%	62 88.6%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 20%	2 4.1%	1 6.3%	4 5.7%
Region of Enrollment (participants) [Number]
United States	4 80%	42 85.7%	15 93.8%	61 87.1%
Spain	0 0%	2 4.1%	1 6.3%	3 4.3%
France	1 20%	5 10.2%	0 0%	6 8.6%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis of ORR was not performed since central radiographic review was not performed, due to inconclusive efficacy at the interim analysis, enrollment was permanently stopped in August 2017.

Arm/Group Title	CUDC-907
Arm/Group Description	RR-DLBCL, including with MYC alterations detected by FISH or by >=40% MYC by IHC CUDC-907
Measure Participants	0

2. Secondary Outcome

Title	Median Progression-free Survival
Description	Efficacy of CUDC-907 in subjects with Relapsed/Refractory MYC-altered DLBCL
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Evaluable population; The number of participants in this table include the evaluable participants which is different from the overall number of participants.

Arm/Group Title	Group A	Group B	Group C
Arm/Group Description	MYC translocation+ and/or MYC gene copy number gain by FISH	MYC expression in > 40% of tumor cells by IHC	MYC translocation- by FISH, and MYC expression in < 40% of tumor cells, and no MYC gene copy number gain by FISH
Measure Participants	2	28	9
Median (95% Confidence Interval) [months]	1.2	2.7	2.6

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Efficacy of CUDC-907 in subjects with Relapsed/Refractory MYC-altered DLBCL
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Evaluable population; The number of participants in this table include the evaluable participants which is different from the overall number of participants.

Arm/Group Title	Group A	Group B	Group C
Arm/Group Description	MYC translocation+ and/or MYC gene copy number gain by FISH	MYC expression in > 40% of tumor cells by IHC	MYC translocation- by FISH, and MYC expression in < 40% of tumor cells, and no MYC gene copy number gain by FISH
Measure Participants	2	28	9
Number [participants]	1 20%	17 34.7%	2 12.5%

4. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	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.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Evaluable population; The number of participants in this table include the evaluable participants which is different from the overall number of participants.

Arm/Group Title	Group A	Group B	Group C
Arm/Group Description	MYC translocation+ and/or MYC gene copy number gain by FISH	MYC expression in > 40% of tumor cells by IHC	MYC translocation- by FISH, and MYC expression in < 40% of tumor cells, and no MYC gene copy number gain by FISH
Measure Participants	2	28	9
Number (95% Confidence Interval) [percentage of participants]	0.0 0%	46.4 94.7%	44.4 277.5%

5. Secondary Outcome

Title	Number of Participants and Severity of Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety Parameters
Description	Number of participants and severity of adverse events (AEs), serious adverse events (SAEs), and other safety parameters in patients receiving CUDC-907.
Time Frame	AEs were collected for each participant for the duration that they remained on the study, on average of 4 months

Outcome Measure Data

Analysis Population Description

Safety Population; The number of participants in this table include the participants evaluable for safety which is different from the overall number of participants.

Arm/Group Title	CUDC-907
Arm/Group Description	RR-DLBCL, including with MYC alterations detected by FISH or by >=40% MYC by IHC CUDC-907
Measure Participants	68
Experienced at least 1 TEAE	68 1360%
Experienced at least 1 study tx-related TEAE	59 1180%
Experienced a Grade <3 TEAE	52 1040%
Experienced a Grade <3 TEAE tx-related	34 680%
Experienced at least 1 tx emergent SAE	30 600%
Experienced a TEAE with outcome of death	17 340%
Experienced a TEAE leading to D/C	11 220%

Adverse Events

Time Frame	AEs were collected for each participant for the duration that they remained on the study, on average of 4 months
Arm/Group Title	CUDC-907
Arm/Group Description	RR-DLBCL, including with MYC alterations detected by FISH or by >=40% MYC by IHC CUDC-907
All Cause Mortality
	CUDC-907
	Affected / at Risk (%)	# Events
Total	17/68 (25%)
Serious Adverse Events
	CUDC-907
	Affected / at Risk (%)	# Events
Total	30/68 (44.1%)
Blood and lymphatic system disorders
Anemia	1/68 (1.5%)	1
Febrile Neutropenia	1/68 (1.5%)	1
Cardiac disorders
Atrial fibrillation	2/68 (2.9%)	2
Gastrointestinal disorders
Diarhhea	3/68 (4.4%)	3
Abdominal Pain	2/68 (2.9%)	2
Abdominal Pain Upper	1/68 (1.5%)	1
Small Intestinal Obstruction	1/68 (1.5%)	1
General disorders
Asthenia	1/68 (1.5%)	1
Disease Progression	1/68 (1.5%)	1
Non-cardiac chest pain	1/68 (1.5%)	1
Pyrexia	1/68 (1.5%)	1
Hepatobiliary disorders
Cholecystitis	1/68 (1.5%)	1
hyperbilirubenemia	1/68 (1.5%)	1
Infections and infestations
Sepsis	3/68 (4.4%)	3
Citrobacter Batremia	1/68 (1.5%)	1
Cytomegalovirus	1/68 (1.5%)	1
Enterococcal	1/68 (1.5%)	1
Pneumonia	1/68 (1.5%)	1
Wound infection	1/68 (1.5%)	1
Injury, poisoning and procedural complications
Tracheal obstruction	1/68 (1.5%)	1
Metabolism and nutrition disorders
Dehydration	3/68 (4.4%)	3
Musculoskeletal and connective tissue disorders
Pain in extremity	1/68 (1.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Diffuse Large B Cell lymphoma	7/68 (10.3%)	7
Lymphoma	3/68 (4.4%)	3
Nervous system disorders
Gullain-Barre Syndrome	1/68 (1.5%)	1
Product Issues
Device occulsion	1/68 (1.5%)	1
Renal and urinary disorders
Acute Kidney Injury	3/68 (4.4%)	3
Respiratory, thoracic and mediastinal disorders
COPD	1/68 (1.5%)	1
Pulmonary Embolism	1/68 (1.5%)	1
Other (Not Including Serious) Adverse Events
	CUDC-907
	Affected / at Risk (%)	# Events
Total	68/68 (100%)
Blood and lymphatic system disorders
Thrombocytopenia	28/68 (41.2%)	28
Anemia	18/68 (26.5%)	18
Neutropenia	14/68 (20.6%)	14
Cardiac disorders
Atrial fibrillation	5/68 (7.4%)	5
Gastrointestinal disorders
Diarrhea	49/68 (72.1%)	49
Nausea	33/68 (48.5%)	33
Vomiting	19/68 (27.9%)	19
Constipation	14/68 (20.6%)	14
Abdominal Pain	12/68 (17.6%)	12
Dyspepsia	4/68 (5.9%)	4
General disorders
Fatigue	24/68 (35.3%)	24
Pyrexia	13/68 (19.1%)	13
Peripheral edema	8/68 (11.8%)	8
Asthensia	5/68 (7.4%)	5
Chills	4/68 (5.9%)	4
Infections and infestations
Upper Respiratory Infection	6/68 (8.8%)	6
Sepsis	4/68 (5.9%)	4
Metabolism and nutrition disorders
Hypokalemia	37/68 (54.4%)	37
Decreased appetite	23/68 (33.8%)	23
Hypomagnesia	27/68 (39.7%)	27
Dehydration	19/68 (27.9%)	19
Hypocalcemia	12/68 (17.6%)	12
Hyperuricemia	13/68 (19.1%)	13
Musculoskeletal and connective tissue disorders
Arthralgia	14/68 (20.6%)	14
Pain in extremity	13/68 (19.1%)	13
Back pain	11/68 (16.2%)	11
Musculoskeletal pain	6/68 (8.8%)	6
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Diffuse Large B Cell lymphoma	7/68 (10.3%)	7
Nervous system disorders
Dizziness	13/68 (19.1%)	13
Headache	6/68 (8.8%)	6
Dysgeusia	5/68 (7.4%)	5
Psychiatric disorders
Insomnia	4/68 (5.9%)	4
Renal and urinary disorders
Acute Kidney Injury	11/68 (16.2%)	11
Respiratory, thoracic and mediastinal disorders
Dyspnea	18/68 (26.5%)	18
Cough	9/68 (13.2%)	9
Oropharyngeal Pain	6/68 (8.8%)	6
Skin and subcutaneous tissue disorders
Pruritus	5/68 (7.4%)	5

Limitations/Caveats

Due to inconclusive efficacy at the interim analysis, enrollment was permanently stopped in August 2017.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.