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

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03542266
• Collaborator: Celgene Corporation (Industry)
• Enrollment: 21
• Locations: 4
• Arm: 1
• Anticipated Duration (Months): 59
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a phase II, multi-center study to determine the efficacy and safety of first-line CC-486 plus CHOP in patients with PTCL who have received no prior systemic therapy. The study has a sample size of 20, and follows two-stage minimax design for primary efficacy analysis.

Condition or Disease	Intervention/Treatment	Phase
Previously Untreated Peripheral T-cell Lymphoma	Drug: CC-486 Administration; Drug: CHOP Administration	Phase 2

Detailed Description

Study Summary:

This is a phase II, multi-center study to determine the efficacy and safety of first-line CC-486 plus CHOP in patients with Peripheral T-cell Lymphoma (PTCL) who have received no prior systemic therapy. The main objective is to determine the complete response rate (CR) of CC486-CHOP in PTCL. CR rate after cycle 6 will be used for the purpose of interim efficacy analysis.

• The study includes 6 cycles (~18 weeks) of treatment and 2 years of follow-up. The projected end date is 12/31/2022. Patients achieving complete remission will be evaluated every 6 months for 2 years or until disease progression. Patients who have disease progression will be contacted every 6 months to assess for survival status.

• Standard dose CHOP will be provided on day 1 of each cycle and repeat every 3 weeks for a total of 6 cycles.

• CC486 at 300 mg daily will be administered orally from day -6 to day 0 for cycle 1 priming, and on days 8-21 following cycles 1-5.

• Patients in CR/PR following 6 cycles of treatment have the option to proceed to consolidative autologous stem cell transplant.

• Will continue on treatment as long as they are responding to therapy and not experiencing unacceptable side effects.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: This is a phase II, multi-center study to determine the efficacy and safety of first-line CC-486 plus CHOP in patients with PTCL who have received no prior systemic therapy. The study has a sample size of 20, and follows two-stage minimax design for primary efficacy analysis.This is a phase II, multi-center study to determine the efficacy and safety of first-line CC-486 plus CHOP in patients with PTCL who have received no prior systemic therapy. The study has a sample size of 20, and follows two-stage minimax design for primary efficacy analysis.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-center Phase II Study of CC486-CHOP in Patients With Previously Untreated Peripheral T-cell Lymphoma
• Actual Study Start Date: Jun 1, 2018
• Actual Primary Completion Date: Mar 25, 2020
• Anticipated Study Completion Date: May 1, 2023

Arms and Interventions

Arm

Intervention/Treatment

Experimental: CC486 +CHOP CC486 +CHOP

Drug: 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.; Other Names: Oral Azacitidine ; Drug: 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

Outcome Measures

Primary Outcome Measures

1. Complete Response Rate [After Cycle 6 at 18 weeks]

   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.

Secondary Outcome Measures

1. Overall Survival [2 years]

   Overall Survival (OS) assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formula. OS will be defined as the time from first treatment day until death.

2. Progression-Free Survival [2 years]

   Progression-free survival (PFS), assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formula. PFS will be defined as the time from first treatment day until objective or symptomatic progression or death.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed diagnosis of PTCL of the following subtypes:

1. Angioimmunoblastic T-cell lymphoma

2. Follicular T-cell lymphoma

3. PTCL/NOS, T-follicular helper (TFH) variant

• No prior systemic therapy for lymphoma

• Measurable disease defined by a tumor mass ≥ 1.5 cm in one dimension and measurable in two dimensions

• ECOG performance status ≤ 2

Exclusion Criteria:

• Known central nervous system (CNS) involvement by lymphoma

• Active viral infection with HIV or hepatitis type B or C (seropositive HBV patients are eligible if they are negative for HBV DNA by PCR and receive concomitant antiviral therapy).

• Prior history of malignancies other than PTCL unless the patient has been disease free for ≥ 5 years from the signing of the ICF.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Moffitt Cancer Center	Tampa	Florida	United States	33612
2	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
3	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
4	Weill Cornell Medicine	New York	New York	United States	10065

Sponsors and Collaborators

• Weill Medical College of Cornell University
• Celgene Corporation

Investigators

• Principal Investigator: Jia Ruan, MD, Ph.D, Weill Medical College of Cornell University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 25, 2020

More Information

Publications

None provided.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT03542266
• Other Study ID Numbers: 1711018777
• First Posted: May 31, 2018
• Last Update Posted: May 19, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Weill Medical College of Cornell University: Peripheral T-cell Lymphoma; Azacitidine; Lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Azacitidine; Cc-486

Study Results

Participant Flow

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
Period Title: Treatment Phase
STARTED	15
COMPLETED	0
NOT COMPLETED	15

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 Participants	21
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 42.9%
>=65 years	12 57.1%
Sex: Female, Male (Count of Participants)
Female	8 38.1%
Male	13 61.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 4.8%
Not Hispanic or Latino	19 90.5%
Unknown or Not Reported	1 4.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	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%
Unknown or Not Reported	5 23.8%
Region of Enrollment (participants) [Number]
United States	21 100%

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
Measure Participants	18
Number [percentage of participants]	75 357.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CC486 +CHOP
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion (percent)
	Estimated Value	75.0
	Confidence Interval	(2-Sided) 95%; 46.5 to 90.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Exact (Clopper-Pearson) 95% confidence interval for complete response rate.

2. Secondary Outcome

Title	Overall Survival
Description	Overall Survival (OS) assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formula. OS will be defined as the time from first treatment day until death.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Progression-Free Survival
Description	Progression-free survival (PFS), assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formula. PFS will be defined as the time from first treatment day until objective or symptomatic progression or death.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From time of informed consent to 28 days post last dose of study drug, approximately 8 months.
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 (%)	# Events
Total	1/21 (4.8%)
Serious Adverse Events
	CC486 +CHOP
	Affected / at Risk (%)	# Events
Total	6/21 (28.6%)
Gastrointestinal disorders
Diarrhea	1/21 (4.8%)
Infections and infestations
Influenza A	1/21 (4.8%)
Lung Infection, COVID-19	1/21 (4.8%)
Investigations
Neutopenic Fever	2/21 (9.5%)
Metabolism and nutrition disorders
Hyponatremia	1/21 (4.8%)
Blood Bilirubin Increase	1/21 (4.8%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	1/21 (4.8%)
Nervous system disorders
Stroke	1/21 (4.8%)
Headache	1/21 (4.8%)
Skin and subcutaneous tissue disorders
Cellulitis	1/21 (4.8%)
Other (Not Including Serious) Adverse Events
	CC486 +CHOP
	Affected / at Risk (%)	# Events
Total	21/21 (100%)
Blood and lymphatic system disorders
Anemia	10/21 (47.6%)
Cardiac disorders
Sinus tachycardia	3/21 (14.3%)
Orthostatic hypotension	3/21 (14.3%)
Chest pain - cardiac	3/21 (14.3%)
Gastrointestinal disorders
Abdominal Pain	7/21 (33.3%)
Constipation	19/21 (90.5%)
Diarrhea	11/21 (52.4%)
Dry Mouth	5/21 (23.8%)
Flatulence	3/21 (14.3%)
Gastroesophageal reflux disease	2/21 (9.5%)
Mucositis Oral	2/21 (9.5%)
Nausea	15/21 (71.4%)
Stomach Pain	2/21 (9.5%)
Vomiting	10/21 (47.6%)
General disorders
Edema limbs	6/21 (28.6%)
Fatigue	14/21 (66.7%)
Fever	3/21 (14.3%)
Generalized weakness	2/21 (9.5%)
Non-cardiac chest pain	4/21 (19%)
Night sweats	2/21 (9.5%)
Weight loss	2/21 (9.5%)
Infections and infestations
Oral Candidiasis	2/21 (9.5%)
Rhinovirus	2/21 (9.5%)
Skin infection	2/21 (9.5%)
Upper respiratory infection	3/21 (14.3%)
Investigations
Alanine aminotransferase increased	3/21 (14.3%)
Aspartate aminotransferase increased	2/21 (9.5%)
Alkaline phosphatase increased	2/21 (9.5%)
Lymphocyte count decreased	13/21 (61.9%)
Neutrophil count decreased	15/21 (71.4%)
Transaminitis	2/21 (9.5%)
Platelet count decreased	11/21 (52.4%)
White blood cell decreased	12/21 (57.1%)
Metabolism and nutrition disorders
Anorexia	6/21 (28.6%)
Hypercalcemia	2/21 (9.5%)
Hypoalbuminemia	3/21 (14.3%)
Hypocalcemia	2/21 (9.5%)
Hyponatremia	3/21 (14.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/21 (14.3%)
Bone pain	3/21 (14.3%)
Myalgia	2/21 (9.5%)
Nervous system disorders
Dizziness	6/21 (28.6%)
Dysgeusia	3/21 (14.3%)
Headache	5/21 (23.8%)
Neuropathy	5/21 (23.8%)
Syncope	2/21 (9.5%)
Psychiatric disorders
Anxiety	4/21 (19%)
Insomnia	2/21 (9.5%)
Respiratory, thoracic and mediastinal disorders
Cough	5/21 (23.8%)
Nasal congestion	5/21 (23.8%)
Rhinorrhea	2/21 (9.5%)
Sore throat	2/21 (9.5%)
Skin and subcutaneous tissue disorders
Alopecia	5/21 (23.8%)
Erythema	2/21 (9.5%)
Pruritus	4/21 (19%)
Rash maculo-papular	3/21 (14.3%)
Vascular disorders
Hypertension	4/21 (19%)
Hypotension	2/21 (9.5%)
Superficial thrombophlebitis	2/21 (9.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.