rituximab: To Demonstrate Equivalence of Pharmacokinetics and Noninferiority of Efficacy for CT-P10 in Comparison With Rituxan

• Sponsor: Celltrion (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02162771
• Collaborator: (none)
• Enrollment: 140
• Arms: 2
• Actual Duration (Months): 53.5

Study Details

Study Description

Brief Summary

This study is a Phase 3 prospective, randomised, parallel-group, active controlled, double blind, multicentre, international study with 2 coprimary endpoints designed to demonstrate equivalence in pharmacokinetics (Part 1), as well as noninferiority in efficacy (Part 2), of CT-P10 to Rituxan when coadministered with CVP and to assess efficacy and safety in patients with advanced (stage III-IV) FL. Part 1 and Part 2 of the study will run in parallel.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Follicular	Biological: Rituxan; Biological: CT-P10; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Prednisone	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomised, Parallel-Group, Active-Controlled, Double-Blind Study to Demonstrate Equivalence of Pharmacokinetics and Noninferiority of Efficacy for CT-P10 in Comparison With Rituxan, Each Administered in Combination With Cyclophosphamide, Vincristine, and Prednisone (CVP) in Patients With Advanced Follicular Lymphoma
• Actual Study Start Date: Jul 14, 2014
• Actual Primary Completion Date: Jan 12, 2016
• Actual Study Completion Date: Dec 29, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CT-P10 Patient treated with CT-P10 (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period. Patients having responses during Core Study Period treated with CT-P10 (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.	Biological: CT-P10; Other Names: Rituximab ; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Prednisone; Other Names: Prednisolone
Active Comparator: Rituxan Patient treated with Rituxan (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period. Patients having responses during Core Study Period treated with Rituxan (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.	Biological: Rituxan; Other Names: Rituximab ; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Prednisone; Other Names: Prednisolone

Outcome Measures

Primary Outcome Measures

1. Area Under the Serum Concentration-time Curve at Steady State (AUCtau) [Core Cycle 4 (Week 12)]

   AUCtau: Area under the plasma drug concentration-time curve within a dosing interval at steady state. PK sampling was done at pre-dose and 1 hour after the end of infusion (EOI) at Core Cycles 1-3 and 5-8. At Core Cycle 4 (i.e. steady state), intensive PK samplings were done as follows: predose, EOI, 1 hour after EOI, 24 hour after EOI, 168 hour after EOI, 336 hour after EOI, 504 hour after EOI. Lastly, one sample at any time of the end of treatment (EOT) 1 visit was obtained.

2. Maximum Serum Concentration at Steady State (Cmax,ss) [Core Cycle 4 (Week 12)]

   Cmax,ss: Maximum concentration of drug in plasma at steady state on administering a fixed dose at equal dosing intervals. PK sampling was done at pre-dose and 1 hour after the end of infusion (EOI) at Core Cycles 1-3 and 5-8. At Core Cycle 4 (i.e. steady state), intensive PK samplings were done as follows: predose, EOI, 1 hour after EOI, 24 hour after EOI, 168 hour after EOI, 336 hour after EOI, 504 hour after EOI. Lastly, one sample at any time of the end of treatment (EOT) 1 visit was obtained.

3. Overall Response Rate (ORR) According to the 1999 International Working Group (IWG) Criteria [During the Core Study Period (up to 8 cycles; Week 24)]

   ORR was defined as the proportion of patients with the best response of complete response (CR), unconfirmed complete response (CRu), or partial response (PR) by central review. Per 1999 IWG criteria, the disease status was assessed by using contrasted CT, and CR, CRu, and PR were defined as followings; CR=Disappearance of all clinical/radiographic evidence of disease: regression of lymph nodes to normal size, absence of B-symptoms, bone marrow involvement, and organomegaly, and normal LDH level; CRu=Regression of measurable disease: >=75% decrease in SPD of target lesions and in each target lesions. no increase in the size of non-target lesions, neither new lesion nor organomegaly measured; PR=Regression of measurable disease: >=50% decrease in SPD of target lesions and no evidence of disease progression.

Secondary Outcome Measures

1. B-cell Kinetics (B-cell Depletion and Recovery) [Cycles 1 to 8 during the Core Study Period]

   B-cell kinetics were demonstrated by median values of B-cell counts (Lower limit of quantification was 20 cells/uL).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Patient is male or female older than 18 years.

2. Patient has histologically confirmed FL according to the World Health Organization 2008 classification (Jaffe 2009); grades 1 to 3a based on local laboratory review.

3. Patient has at least 1 measurable tumour mass that has not previously been irradiated, and the mass must be:

• greater than 1.5 cm in the longest dimension or

• between 1.1 and 1.5 cm in the longest dimension and greater than 1.0 cm in the shortest axis

1. Patient has confirmed CD20+ lymphoma, as assessed by local laboratory review. (Tissue obtained within 6 months before Day 1 of Cycle 1 will be reviewed by a central independent reviewer to detect pathological type.)

2. Patient has Ann Arbor stage III or IV disease.

Exclusion Criteria:

1. Patient has received rituximab (or a rituximab biosimilar), cyclophosphamide, or vincristine.

2. Patient has allergies or hypersensitivity to murine, chimeric, human or humanised proteins, cyclophosphamide, vincristine, or prednisone.

3. Patient has evidence of histological transformation to high-grade or diffuse large B-cell lymphoma.

4. Patient has known central nervous system involvement.

5. Patient has received previous treatment for NHL:

• Previous treatment including chemotherapy, radiotherapy, immunotherapy, and/or surgery (except previous biopsy)

• All doses of corticoid therapy for treatment of NHL

• Corticoid therapy during the previous 4 weeks from Day 1 of Cycle 1 with prednisone >20 mg per day for the treatment for any purpose

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Celltrion

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Celltrion
• ClinicalTrials.gov Identifier: NCT02162771
• Other Study ID Numbers: CT-P10 3.3; 2013-004493-96
• First Posted: Jun 13, 2014
• Last Update Posted: Jan 29, 2020
• Last Verified: Jan 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Keywords provided by Celltrion: Advanced Follicular Lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Follicular; Prednisone; Prednisolone; Cyclophosphamide; Rituximab; Vincristine

Study Results

Participant Flow

Pre-assignment Detail	A total of 184 participants were screened for the study. Of those, 44 participants failed screening and 140 participants were enrolled in the study.

Arm/Group Title	CT-P10	Rituxan
Arm/Group Description	Patient treated with CT-P10 (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period. Patients having responses during Core Study Period treated with CT-P10 (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.	Patient treated with Rituxan (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period. Patients having responses during Core Study Period treated with Rituxan (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.
Period Title: Core Study Period (Part 2)
STARTED	70	70
COMPLETED	62	62
NOT COMPLETED	8	8
Period Title: Core Study Period (Part 2)
STARTED	62	60
COMPLETED	46	38
NOT COMPLETED	16	22

Baseline Characteristics

Arm/Group Title	CT-P10	Rituxan	Total
Arm/Group Description	Patient treated with CT-P10 (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period. Patients having responses during Core Study Period treated with CT-P10 (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.	Patient treated with Rituxan (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period. Patients having responses during Core Study Period treated with Rituxan (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.	Total of all reporting groups
Overall Participants	70	70	140
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57.0	58.5	57.5
Sex: Female, Male (Count of Participants)
Female	40 57.1%	37 52.9%	77 55%
Male	30 42.9%	33 47.1%	63 45%

Outcome Measures

1. Primary Outcome

Title	Area Under the Serum Concentration-time Curve at Steady State (AUCtau)
Description	AUCtau: Area under the plasma drug concentration-time curve within a dosing interval at steady state. PK sampling was done at pre-dose and 1 hour after the end of infusion (EOI) at Core Cycles 1-3 and 5-8. At Core Cycle 4 (i.e. steady state), intensive PK samplings were done as follows: predose, EOI, 1 hour after EOI, 24 hour after EOI, 168 hour after EOI, 336 hour after EOI, 504 hour after EOI. Lastly, one sample at any time of the end of treatment (EOT) 1 visit was obtained.
Time Frame	Core Cycle 4 (Week 12)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population consisted of all patients who had at least 1 posttreatment PK concentration result after receiving at least 1 dose of study drug (CT-P10 or Rituxan) in Part 1. Patients considered outliers identified by a robust regression model (95% CI) were excluded from the analysis.

Arm/Group Title	CT-P10	Rituxan
Arm/Group Description	Patient treated with CT-P10 (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period. Patients having responses during Core Study Period treated with CT-P10 (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.	Patient treated with Rituxan (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period. Patients having responses during Core Study Period treated with Rituxan (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.
Measure Participants	50	56
Geometric Mean (Standard Error) [h*ug/mL]	41002.43 (1.136)	40099.08 (1.143)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT-P10, Rituxan
	Comments	Equivalence in AUCtau between CT-P10 and Rituxan
	Type of Statistical Test	Equivalence
	Comments	The 90% CIs of the ratios of geometric means of log-transformed values were used to assess the bioequivalence between CT-P10 and Rituxan (bioequivalence range of 80% to 125%)
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric least square means
	Estimated Value	102.25
	Confidence Interval	(2-Sided) 90%; 94.05 to 111.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Maximum Serum Concentration at Steady State (Cmax,ss)
Description	Cmax,ss: Maximum concentration of drug in plasma at steady state on administering a fixed dose at equal dosing intervals. PK sampling was done at pre-dose and 1 hour after the end of infusion (EOI) at Core Cycles 1-3 and 5-8. At Core Cycle 4 (i.e. steady state), intensive PK samplings were done as follows: predose, EOI, 1 hour after EOI, 24 hour after EOI, 168 hour after EOI, 336 hour after EOI, 504 hour after EOI. Lastly, one sample at any time of the end of treatment (EOT) 1 visit was obtained.
Time Frame	Core Cycle 4 (Week 12)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population consisted of all patients who had at least 1 posttreatment PK concentration result after receiving at least 1 dose of study drug (CT-P10 or Rituxan) in Part 1. Patients considered outliers identified by a robust regression model (95% CI) were excluded from the analysis.

Arm/Group Title	CT-P10	Rituxan
Arm/Group Description	Patient treated with CT-P10 (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period. Patients having responses during Core Study Period treated with CT-P10 (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.	Patient treated with Rituxan (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period. Patients having responses during Core Study Period treated with Rituxan (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.
Measure Participants	53	56
Geometric Mean (Standard Error) [ug/mL]	256.19 (1.115)	254.49 (1.120)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT-P10, Rituxan
	Comments	Equivalence in Cmax,ss between CT-P10 and Rituxan
	Type of Statistical Test	Equivalence
	Comments	The 90% CIs of the ratios of geometric means of log-transformed transformed values were used to assess the bioequivalence between CT-P10 and Rituxan (bioequivalence range of 80% to 125%)
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric least square means
	Estimated Value	100.67
	Confidence Interval	(2-Sided) 90%; 93.84 to 108.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Overall Response Rate (ORR) According to the 1999 International Working Group (IWG) Criteria
Description	ORR was defined as the proportion of patients with the best response of complete response (CR), unconfirmed complete response (CRu), or partial response (PR) by central review. Per 1999 IWG criteria, the disease status was assessed by using contrasted CT, and CR, CRu, and PR were defined as followings; CR=Disappearance of all clinical/radiographic evidence of disease: regression of lymph nodes to normal size, absence of B-symptoms, bone marrow involvement, and organomegaly, and normal LDH level; CRu=Regression of measurable disease: >=75% decrease in SPD of target lesions and in each target lesions. no increase in the size of non-target lesions, neither new lesion nor organomegaly measured; PR=Regression of measurable disease: >=50% decrease in SPD of target lesions and no evidence of disease progression.
Time Frame	During the Core Study Period (up to 8 cycles; Week 24)

Outcome Measure Data

Analysis Population Description

Efficacy population consisted of all patients who had at least 1 response evaluation after receiving at least 1 treatment cycle in the Core Study Period without any major protocol deviation that was relevant to the efficacy endpoint in Part 2.

Arm/Group Title	CT-P10	Rituxan
Arm/Group Description	Patient treated with CT-P10 (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period. Patients having responses during Core Study Period treated with CT-P10 (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.	Patient treated with Rituxan (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period. Patients having responses during Core Study Period treated with Rituxan (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.
Measure Participants	66	68
Count of Participants [Participants]	64 91.4%	63 90%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CT-P10, Rituxan
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin of -7% was predefined.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Point estimate difference
	Estimated Value	4.3
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	B-cell Kinetics (B-cell Depletion and Recovery)
Description	B-cell kinetics were demonstrated by median values of B-cell counts (Lower limit of quantification was 20 cells/uL).
Time Frame	Cycles 1 to 8 during the Core Study Period

Outcome Measure Data

Analysis Population Description

Pharmacodynamic (PD) population consisted of all patients who had at least 1 posttreatment PD result after receiving at least 1 dose of study drug (CT-P10 or Rituxan) without any major protocol deviation that was relevant to the PD endpoint in Part 2.

Arm/Group Title	CT-P10	Rituxan
Arm/Group Description	Patient treated with CT-P10 (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period. Patients having responses during Core Study Period treated with CT-P10 (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.	Patient treated with Rituxan (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period. Patients having responses during Core Study Period treated with Rituxan (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.
Measure Participants	70	70
Core Cycle 1 (Predose)	92.5	62.0
Core Cycle 1 (1 hour after the end of infusion)	20.0	20.0
Core Cycle 2 (Predose)	20.0	20.0
Core Cycle 3 (Predose)	20.0	20.0
Core Cycle 4 (Predose)	20.0	20.0
Core Cycle 5 (Predose)	20.0	20.0
Core Cycle 6 (Predose)	20.0	20.0
Core Cycle 7 (Predose)	20.0	20.0
Core Cycle 8 (Predose)	20.0	20.0

Adverse Events

Time Frame	Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from last dose of the study drug, regardless of relationship to the study drug (a median follow up of 39.9 months).
Adverse Event Reporting Description	All TESAEs and non-serious AEs reported for more than 5% of the patients in either treatment group were summarized for the safety population. Safety population consisted of all patients who received at least 1 dose of the study drug (CT-P10 or Rituxan). Grading for severity and terminology of AEs were described according to the CTCAE Version 4.0.
Arm/Group Title	CT-P10		Rituxan
Arm/Group Description	Patient treated with CT-P10 (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period. Patients having responses during Core Study Period treated with CT-P10 (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.		Patient treated with Rituxan (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period. Patients having responses during Core Study Period treated with Rituxan (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period.
All Cause Mortality
	CT-P10		Rituxan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	CT-P10		Rituxan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/70 (34.3%)		13/70 (18.6%)
Blood and lymphatic system disorders
Anaemia	1/70 (1.4%)		0/70 (0%)
Febrile neutropenia	2/70 (2.9%)		3/70 (4.3%)
Leukopenia	0/70 (0%)		1/70 (1.4%)
Neutropenia	1/70 (1.4%)		1/70 (1.4%)
Pancytopenia	1/70 (1.4%)		0/70 (0%)
Cardiac disorders
Atrial fibrillation	1/70 (1.4%)		0/70 (0%)
Tachycardia	0/70 (0%)		1/70 (1.4%)
Gastrointestinal disorders
Constipation	1/70 (1.4%)		0/70 (0%)
Diarrhea	0/70 (0%)		1/70 (1.4%)
Ileus	0/70 (0%)		1/70 (1.4%)
Small intestinal perforation	1/70 (1.4%)		0/70 (0%)
General disorders
Pyrexia	0/70 (0%)		1/70 (1.4%)
Hepatobiliary disorders
Cholecystitis	1/70 (1.4%)		0/70 (0%)
Immune system disorders
Anaphylactic shock	1/70 (1.4%)		0/70 (0%)
Infections and infestations
Abdominal infection	1/70 (1.4%)		0/70 (0%)
Appendicitis	1/70 (1.4%)		0/70 (0%)
Campylobacter gastroenteritis	1/70 (1.4%)		0/70 (0%)
Encephalitis	0/70 (0%)		1/70 (1.4%)
Herpes virus infection	1/70 (1.4%)		0/70 (0%)
Lower respiratory tract infection	1/70 (1.4%)		2/70 (2.9%)
Pneumonia	4/70 (5.7%)		1/70 (1.4%)
Sialodenitis	1/70 (1.4%)		0/70 (0%)
Upper respiratory tract infection	0/70 (0%)		2/70 (2.9%)
Injury, poisoning and procedural complications
Fracture	1/70 (1.4%)		0/70 (0%)
Injury	1/70 (1.4%)		0/70 (0%)
Post procedural fistula	1/70 (1.4%)		0/70 (0%)
Subdural haematoma	0/70 (0%)		1/70 (1.4%)
Investigations
Liver function test abnormal	1/70 (1.4%)		0/70 (0%)
Metabolism and nutrition disorders
Hypoalbuminaemia	1/70 (1.4%)		0/70 (0%)
Hypocalcaemia	1/70 (1.4%)		0/70 (0%)
Hypomagnesaemia	1/70 (1.4%)		0/70 (0%)
Tumour lysis syndrome	1/70 (1.4%)		0/70 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma gastric	1/70 (1.4%)		0/70 (0%)
Hepatocellular carcinoma	1/70 (1.4%)		0/70 (0%)
Invasive lobular breast carcinoma	1/70 (1.4%)		0/70 (0%)
Prostate cancer metastatic	1/70 (1.4%)		0/70 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/70 (0%)		1/70 (1.4%)
Chronic obstructive pulmonary disease	2/70 (2.9%)		1/70 (1.4%)
Pleural effusion	1/70 (1.4%)		0/70 (0%)
Pulmonary embolism	1/70 (1.4%)		0/70 (0%)
Respiratory failure	1/70 (1.4%)		0/70 (0%)
Vascular disorders
Deep vein thrombosis	1/70 (1.4%)		0/70 (0%)
Hypertension	1/70 (1.4%)		0/70 (0%)
Peripheral ischaemia	0/70 (0%)		1/70 (1.4%)
Thrombophlebitis	0/70 (0%)		1/70 (1.4%)
Other (Not Including Serious) Adverse Events
	CT-P10		Rituxan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	58/70 (82.9%)		57/70 (81.4%)
Blood and lymphatic system disorders
Anaemia	6/70 (8.6%)		5/70 (7.1%)
Neutropenia	27/70 (38.6%)		20/70 (28.6%)
Gastrointestinal disorders
Abdominal pain	8/70 (11.4%)		11/70 (15.7%)
Constipation	12/70 (17.1%)		10/70 (14.3%)
Diarrhoea	6/70 (8.6%)		7/70 (10%)
Nausea	9/70 (12.9%)		7/70 (10%)
Stomatitis	2/70 (2.9%)		4/70 (5.7%)
General disorders
Asthenia	5/70 (7.1%)		8/70 (11.4%)
Fatigue	6/70 (8.6%)		8/70 (11.4%)
Oedema	5/70 (7.1%)		3/70 (4.3%)
Pyrexia	3/70 (4.3%)		6/70 (8.6%)
Infections and infestations
Fungal infection	4/70 (5.7%)		4/70 (5.7%)
Influenza	2/70 (2.9%)		4/70 (5.7%)
Lower respiratory tract infection	7/70 (10%)		1/70 (1.4%)
Sinusitis	5/70 (7.1%)		2/70 (2.9%)
Upper respiratory tract infection	14/70 (20%)		18/70 (25.7%)
Urinary tract infection	6/70 (8.6%)		6/70 (8.6%)
Injury, poisoning and procedural complications
Fracture	4/70 (5.7%)		1/70 (1.4%)
Infusion related reaction	16/70 (22.9%)		19/70 (27.1%)
Metabolism and nutrition disorders
Decreased appetite	0/70 (0%)		6/70 (8.6%)
Hyperglycaemia	2/70 (2.9%)		5/70 (7.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/70 (10%)		4/70 (5.7%)
Back pain	2/70 (2.9%)		12/70 (17.1%)
Myalgia	6/70 (8.6%)		2/70 (2.9%)
Nervous system disorders
Dizziness	4/70 (5.7%)		5/70 (7.1%)
Headache	4/70 (5.7%)		6/70 (8.6%)
Hypoaesthesia	6/70 (8.6%)		2/70 (2.9%)
Neuropathy peripheral	10/70 (14.3%)		12/70 (17.1%)
Paraesthesia	3/70 (4.3%)		8/70 (11.4%)
Psychiatric disorders
Insomnia	2/70 (2.9%)		6/70 (8.6%)
Respiratory, thoracic and mediastinal disorders
Cough	6/70 (8.6%)		5/70 (7.1%)
Dyspnoea	4/70 (5.7%)		1/70 (1.4%)
Oropharyngeal pain	1/70 (1.4%)		4/70 (5.7%)
Skin and subcutaneous tissue disorders
Alopecia	10/70 (14.3%)		5/70 (7.1%)
Vascular disorders
Hypertension	6/70 (8.6%)		3/70 (4.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Confidentiality and non-disclosure agreement (CDA) was executed between Celltrion, Inc. and some PIs who have participated in publications funded by the sponsor for academic purposes for a period that is more than 180 days from the time submitted to the sponsor for review.