CC486-CHOP in Patients With Previously Untreated Peripheral T-cell Lymphoma

• ClinicalTrials.gov Identifier: NCT03542266
• Recruitment Status: Completed
• First Posted: May 31, 2018
• Results First Posted: May 20, 2021
• Last Update Posted: August 22, 2023
• Sponsor: Weill Medical College of Cornell University
• Collaborator: Celgene Corporation
• Information provided by (Responsible Party): Weill Medical College of Cornell University

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Previously Untreated Peripheral T-cell Lymphoma
• Interventions: Drug: CC-486 Administration; Drug: CHOP Administration
• Enrollment: 21

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	CC486 +CHOP
Arm/Group Description	CC486 +CHOP CC-486 Administration: CC-486 at 300 mg once daily is to be administered Cycle 1, Day -6 to 0 and Cycles 1 to 5, Day 8 to 21. Antiemetic prophylaxis is recommended before dosing. All efforts should be made to administer CC-486 on all scheduled days of the Cycle 1 priming dosing (7 days, Cycle 1 Day -6 to Cycle 1 Day 0) and the Cycle 1-5 dosing (14 days, Day 8-21). A dose missed earlier in a day can be administered later that day as long as it is taken at least 8 hours before the next scheduled dose. Any missed dose should not be taken beyond the last scheduled day of CC-486 administration for the cycle, but should be returned by the subject for CC 486 accountability. If vomiting occurs after a dose of CC-486 is administrated, that dose should not be made up later that day. CHOP Administration: CHOP is to be administered on Days 1 to 5 of Cycles 1-6. Chemotherapy can be administer within +72h or -24h of Day 1 of each scheduled Cycle. Preparation and infusion rate are according to the package insert and local practice. The doses to be used are: Cyclophosphamide: 750 mg/m2 IV on day 1 Doxorubicin: 50 mg/m2 IV on day 1 Vincristine: 1.4 mg/m2 IV (not to exceed 2.0 mg total) on day 1 Prednisone: 100 mg PO days 1-5
Period Title: Treatment Phase
Started	21
Completed	18
Not Completed	3
Reason Not Completed
Withdrawal by Subject	1
Adverse Event	1
PD	1
Period Title: Post-treatment Follow-up Phase
Started	15 [1]
Completed	0
Not Completed	15
[1] Three subjects did not enter follow-up: 1 had PD at EOT, 2 withdrew consent

Baseline Characteristics

Arm/Group Title		CC486 +CHOP
Arm/Group Description		CC486 +CHOP CC-486 Administration: CC-486 at 300 mg once daily is to be administered Cycle 1, Day -6 to 0 and Cycles 1 to 5, Day 8 to 21. Antiemetic prophylaxis is recommended before dosing. All efforts should be made to administer CC-486 on all scheduled days of the Cycle 1 priming dosing (7 days, Cycle 1 Day -6 to Cycle 1 Day 0) and the Cycle 1-5 dosing (14 days, Day 8-21). A dose missed earlier in a day can be administered later that day as long as it is taken at least 8 hours before the next scheduled dose. Any missed dose should not be taken beyond the last scheduled day of CC-486 administration for the cycle, but should be returned by the subject for CC 486 accountability. If vomiting occurs after a dose of CC-486 is administrated, that dose should not be made up later that day. CHOP Administration: CHOP is to be administered on Days 1 to 5 of Cycles 1-6. Chemotherapy can be administer within +72h or -24h of Day 1 of each scheduled Cycle. Preparation and infusion rate are according to the package insert and local practice. The doses to be used are: Cyclophosphamide: 750 mg/m2 IV on day 1 Doxorubicin: 50 mg/m2 IV on day 1 Vincristine: 1.4 mg/m2 IV (not to exceed 2.0 mg total) on day 1 Prednisone: 100 mg PO days 1-5
Overall Number of Baseline Participants		21
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	21 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	9 42.9%
	>=65 years	12 57.1%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	21 participants
	Female	8 38.1%
	Male	13 61.9%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	21 participants
	Hispanic or Latino	1 4.8%
	Not Hispanic or Latino	19 90.5%
	Unknown or Not Reported	1 4.8%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	21 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	1 4.8%
	Black or African American	1 4.8%
	White	14 66.7%
	More than one race	0 0.0%
	Unknown or Not Reported	5 23.8%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	21 participants
		21

Outcome Measures

1. Primary Outcome

Title	Complete Response Rate
Description	Complete response rate (CR) of CC486-CHOP in PTCL by Lugano Criteria for target lesions, and the Deauville Criteria (5 point scale) assessed by PET or CT; CR (complete metabolic or radiologic response) defined as Deauville score of 1, 2 or 3 by PET or regression of all target lesions to < 1.5cm in longest diameter by CT.
Time Frame	After Cycle 6 at 18 weeks

Outcome Measure Data

Analysis Population Description

3 of 21 participants did not complete treatment as outlined in the Participant Flow section; these subject were unevaluable and not included in analysis.

Arm/Group Title	CC486 +CHOP
Arm/Group Description:	CC486 +CHOP CC-486 Administration: CC-486 at 300 mg once daily is to be administered Cycle 1, Day -6 to 0 and Cycles 1 to 5, Day 8 to 21. Antiemetic prophylaxis is recommended before dosing. All efforts should be made to administer CC-486 on all scheduled days of the Cycle 1 priming dosing (7 days, Cycle 1 Day -6 to Cycle 1 Day 0) and the Cycle 1-5 dosing (14 days, Day 8-21). A dose missed earlier in a day can be administered later that day as long as it is taken at least 8 hours before the next scheduled dose. Any missed dose should not be taken beyond the last scheduled day of CC-486 administration for the cycle, but should be returned by the subject for CC 486 accountability. If vomiting occurs after a dose of CC-486 is administrated, that dose should not be made up later that day. CHOP Administration: CHOP is to be administered on Days 1 to 5 of Cycles 1-6. Chemotherapy can be administer within +72h or -24h of Day 1 of each scheduled Cycle. Preparation and infusion rate are according to the package insert and local practice. The doses to be used are: Cyclophosphamide: 750 mg/m2 IV on day 1 Doxorubicin: 50 mg/m2 IV on day 1 Vincristine: 1.4 mg/m2 IV (not to exceed 2.0 mg total) on day 1 Prednisone: 100 mg PO days 1-5
Overall Number of Participants Analyzed	18
Measure Type: Number; Unit of Measure: percentage of participants
	75

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CC486 +CHOP
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Proportion (percent)
	Estimated Value	75.0
	Confidence Interval	(2-Sided) 95%; 46.5 to 90.3
	Estimation Comments	Exact (Clopper-Pearson) 95% confidence interval for complete response rate.

2. Secondary Outcome

Title	Kaplan-Meier Overall Survival
Description	Overall Survival (OS) assessed by Kaplan-Meier survival analysis. The Kaplan-Meier overall survival estimate at 2 years (with 95% confidence interval) is reported. OS defined as the time from first treatment day until death (or until last follow-up if alive).
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

1 patient had missing overall survival information.

Arm/Group Title	CC486 +CHOP
Arm/Group Description:	CC486 +CHOP CC-486 Administration: CC-486 at 300 mg once daily is to be administered Cycle 1, Day -6 to 0 and Cycles 1 to 5, Day 8 to 21. Antiemetic prophylaxis is recommended before dosing. All efforts should be made to administer CC-486 on all scheduled days of the Cycle 1 priming dosing (7 days, Cycle 1 Day -6 to Cycle 1 Day 0) and the Cycle 1-5 dosing (14 days, Day 8-21). A dose missed earlier in a day can be administered later that day as long as it is taken at least 8 hours before the next scheduled dose. Any missed dose should not be taken beyond the last scheduled day of CC-486 administration for the cycle, but should be returned by the subject for CC 486 accountability. If vomiting occurs after a dose of CC-486 is administrated, that dose should not be made up later that day. CHOP Administration: CHOP is to be administered on Days 1 to 5 of Cycles 1-6. Chemotherapy can be administer within +72h or -24h of Day 1 of each scheduled Cycle. Preparation and infusion rate are according to the package insert and local practice. The doses to be used are: Cyclophosphamide: 750 mg/m2 IV on day 1 Doxorubicin: 50 mg/m2 IV on day 1 Vincristine: 1.4 mg/m2 IV (not to exceed 2.0 mg total) on day 1 Prednisone: 100 mg PO days 1-5
Overall Number of Participants Analyzed	20
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	68.0; (46.7 to 89.2)

3. Secondary Outcome

Title	Kaplan-Meier Progression-Free Survival
Description	Progression-free survival (PFS) assessed by Kaplan-Meier survival analysis. The Kaplan-Meier progression-free survival estimate at 2 years (with 95% confidence interval) is reported. PFS defined as the time from first treatment day until objective or symptomatic progression or death (or date of last follow-up if no progression/death).
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

1 participant had missing progression-free survival information.

Arm/Group Title	CC486 +CHOP
Arm/Group Description:	CC486 +CHOP CC-486 Administration: CC-486 at 300 mg once daily is to be administered Cycle 1, Day -6 to 0 and Cycles 1 to 5, Day 8 to 21. Antiemetic prophylaxis is recommended before dosing. All efforts should be made to administer CC-486 on all scheduled days of the Cycle 1 priming dosing (7 days, Cycle 1 Day -6 to Cycle 1 Day 0) and the Cycle 1-5 dosing (14 days, Day 8-21). A dose missed earlier in a day can be administered later that day as long as it is taken at least 8 hours before the next scheduled dose. Any missed dose should not be taken beyond the last scheduled day of CC-486 administration for the cycle, but should be returned by the subject for CC 486 accountability. If vomiting occurs after a dose of CC-486 is administrated, that dose should not be made up later that day. CHOP Administration: CHOP is to be administered on Days 1 to 5 of Cycles 1-6. Chemotherapy can be administer within +72h or -24h of Day 1 of each scheduled Cycle. Preparation and infusion rate are according to the package insert and local practice. The doses to be used are: Cyclophosphamide: 750 mg/m2 IV on day 1 Doxorubicin: 50 mg/m2 IV on day 1 Vincristine: 1.4 mg/m2 IV (not to exceed 2.0 mg total) on day 1 Prednisone: 100 mg PO days 1-5
Overall Number of Participants Analyzed	20
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	65.8; (43.4 to 88.1)

Adverse Events

Time Frame	From time of informed consent to 28 days post last dose of study drug, approximately 8 months.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	CC486 +CHOP
Arm/Group Description	CC486 +CHOP CC-486 Administration: CC-486 at 300 mg once daily is to be administered Cycle 1, Day -6 to 0 and Cycles 1 to 5, Day 8 to 21. Antiemetic prophylaxis is recommended before dosing. All efforts should be made to administer CC-486 on all scheduled days of the Cycle 1 priming dosing (7 days, Cycle 1 Day -6 to Cycle 1 Day 0) and the Cycle 1-5 dosing (14 days, Day 8-21). A dose missed earlier in a day can be administered later that day as long as it is taken at least 8 hours before the next scheduled dose. Any missed dose should not be taken beyond the last scheduled day of CC-486 administration for the cycle, but should be returned by the subject for CC 486 accountability. If vomiting occurs after a dose of CC-486 is administrated, that dose should not be made up later that day. CHOP Administration: CHOP is to be administered on Days 1 to 5 of Cycles 1-6. Chemotherapy can be administer within +72h or -24h of Day 1 of each scheduled Cycle. Preparation and infusion rate are according to the package insert and local practice. The doses to be used are: Cyclophosphamide: 750 mg/m2 IV on day 1 Doxorubicin: 50 mg/m2 IV on day 1 Vincristine: 1.4 mg/m2 IV (not to exceed 2.0 mg total) on day 1 Prednisone: 100 mg PO days 1-5
All-Cause Mortality
	CC486 +CHOP
	Affected / at Risk (%)
Total	1/21 (4.76%)
Serious Adverse Events
	CC486 +CHOP
	Affected / at Risk (%)
Total	6/21 (28.57%)
Gastrointestinal disorders
Diarrhea *	1/21 (4.76%)
Infections and infestations
Influenza A *	1/21 (4.76%)
Lung Infection, COVID-19 *	1/21 (4.76%)
Investigations
Neutopenic Fever *	2/21 (9.52%)
Metabolism and nutrition disorders
Hyponatremia *	1/21 (4.76%)
Blood Bilirubin Increase *	1/21 (4.76%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness *	1/21 (4.76%)
Nervous system disorders
Stroke *	1/21 (4.76%)
Headache *	1/21 (4.76%)
Skin and subcutaneous tissue disorders
Cellulitis *	1/21 (4.76%)
* Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	CC486 +CHOP
	Affected / at Risk (%)
Total	21/21 (100.00%)
Blood and lymphatic system disorders
Anemia †	10/21 (47.62%)
Cardiac disorders
Sinus tachycardia †	3/21 (14.29%)
Orthostatic hypotension †	3/21 (14.29%)
Chest pain - cardiac †	3/21 (14.29%)
Gastrointestinal disorders
Abdominal Pain †	7/21 (33.33%)
Constipation †	19/21 (90.48%)
Diarrhea †	11/21 (52.38%)
Dry Mouth †	5/21 (23.81%)
Flatulence †	3/21 (14.29%)
Gastroesophageal reflux disease †	2/21 (9.52%)
Mucositis Oral †	2/21 (9.52%)
Nausea †	15/21 (71.43%)
Stomach Pain †	2/21 (9.52%)
Vomiting †	10/21 (47.62%)
General disorders
Edema limbs †	6/21 (28.57%)
Fatigue †	14/21 (66.67%)
Fever †	3/21 (14.29%)
Generalized weakness †	2/21 (9.52%)
Non-cardiac chest pain †	4/21 (19.05%)
Night sweats †	2/21 (9.52%)
Weight loss †	2/21 (9.52%)
Infections and infestations
Oral Candidiasis †	2/21 (9.52%)
Rhinovirus †	2/21 (9.52%)
Skin infection †	2/21 (9.52%)
Upper respiratory infection †	3/21 (14.29%)
Investigations
Alanine aminotransferase increased †	3/21 (14.29%)
Aspartate aminotransferase increased †	2/21 (9.52%)
Alkaline phosphatase increased †	2/21 (9.52%)
Lymphocyte count decreased †	13/21 (61.90%)
Neutrophil count decreased †	15/21 (71.43%)
Transaminitis †	2/21 (9.52%)
Platelet count decreased †	11/21 (52.38%)
White blood cell decreased †	12/21 (57.14%)
Metabolism and nutrition disorders
Anorexia †	6/21 (28.57%)
Hypercalcemia †	2/21 (9.52%)
Hypoalbuminemia †	3/21 (14.29%)
Hypocalcemia †	2/21 (9.52%)
Hyponatremia †	3/21 (14.29%)
Musculoskeletal and connective tissue disorders
Arthralgia †	3/21 (14.29%)
Bone pain †	3/21 (14.29%)
Myalgia †	2/21 (9.52%)
Nervous system disorders
Dizziness †	6/21 (28.57%)
Dysgeusia †	3/21 (14.29%)
Headache †	5/21 (23.81%)
Neuropathy †	5/21 (23.81%)
Syncope †	2/21 (9.52%)
Psychiatric disorders
Anxiety †	4/21 (19.05%)
Insomnia †	2/21 (9.52%)
Respiratory, thoracic and mediastinal disorders
Cough †	5/21 (23.81%)
Nasal congestion †	5/21 (23.81%)
Rhinorrhea †	2/21 (9.52%)
Sore throat †	2/21 (9.52%)
Skin and subcutaneous tissue disorders
Alopecia †	5/21 (23.81%)
Erythema †	2/21 (9.52%)
Pruritus †	4/21 (19.05%)
Rash maculo-papular †	3/21 (14.29%)
Vascular disorders
Hypertension †	4/21 (19.05%)
Hypotension †	2/21 (9.52%)
Superficial thrombophlebitis †	2/21 (9.52%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Jia Ruan, MD, PhD
• Organization: Weill Cornell Medical College
• Phone: 646-962-2064
• EMail: jruan@med.cornell.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Yoon SE, Cho J, Kim YJ, Kim SJ, Kim WS. Real-World Efficacy of 5-Azacytidine as Salvage Chemotherapy for Angioimmunoblastic T-cell Lymphoma. Clin Lymphoma Myeloma Leuk. 2022 Nov;22(11):e972-e980. doi: 10.1016/j.clml.2022.07.009. Epub 2022 Jul 17.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT03542266
• Other Study ID Numbers: 1711018777
• First Submitted: May 18, 2018
• First Posted: May 31, 2018
• Results First Submitted: March 10, 2021
• Results First Posted: May 20, 2021
• Last Update Posted: August 22, 2023