JASMINE: Study to Assess if ABP798 is Safe & Effective in Treating Non Hodgkin Lymphoma Compared to Rituximab

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02747043
• Collaborator: (none)
• Enrollment: 256
• Locations: 98
• Arms: 2
• Actual Duration (Months): 37.1
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This was a randomized, double-blind, active-controlled, multiple-dose, clinical similarity study to evaluate the efficacy, pharmacokinetics, pharmacodynamics, safety, tolerability and immunogenicity of ABP 798 compared with rituximab in subjects with grade 1, 2, or 3a follicular B-cell NHL and low tumor burden.

Subjects were randomized in a 1:1 ratio to receive a 375 mg/m^2 intravenous infusion of either ABP 798 or rituximab once weekly for 4 weeks followed by dosing at weeks 12 and 20.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Non-Hodgkin	Biological: ABP 798; Biological: Rituximab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 256 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind Study Evaluating the Efficacy, Safety and Immunogenicity of ABP 798 Compared With Rituximab in Subjects With CD20 Positive B-Cell Non-Hodgkin Lymphoma (NHL)
• Actual Study Start Date: May 25, 2016
• Actual Primary Completion Date: Jun 28, 2019
• Actual Study Completion Date: Jun 28, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ABP 798 ABP 798 was administered at a dose of 375 mg/m^2 as an intravenous (IV) infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.	Biological: ABP 798; ABP 798 was supplied as a sterile, preservative-free liquid concentrate for IV infusion at a concentration of 10 mg/mL in either 100 mg/10 mL or 500 mg/50 mL single-dose vials. Subjects were to receive premedications before each infusion. Premedications were to be given according to local practice for administration of rituximab therapy.; Other Names: biosimilar to rituximab
Active Comparator: Rituximab Rituximab was administered at a dose of 375 mg/m^2 as an IV infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.	Biological: Rituximab; Rituximab was procured from commercial supplies in the US and was supplied as a sterile, clear, colorless, preservative-free liquid concentrate for IV infusion at a concentration of 10 mg/mL in either 100-mg/10 mL or 500-mg/50 mL single-dose vials. Subjects were to receive premedications before each infusion. Premedications were to be given according to local practice for administration of rituximab therapy.; Other Names: Rituxan

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Responded (Overall Response Rate - ORR) by Week 28 Based on Independent Central Assessment of Disease [Post treatment up to Week 28]

   Overall response within the first treatment cycle was assessed according to International Working Group - Non-Hodgkin Lymphoma criteria (IWG-NHL criteria [Cheson et al, 1999]) by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement), and bone marrow biopsy (to assess bone marrow infiltration). ORR was the percentage of participants with a best overall response of complete response (CR), unconfirmed complete response (CRu) or partial response (PR). Participants that do not meet the criteria for response were considered non-responders. CR was defined as no evidence of disease. CRu showed nodes in the original sum of the products (SPD) regressed by >75% and/or indeterminate bone marrow results. PR was a ≥ 50% decrease in SPD of the six largest dominant nodes; >=50% decrease in liver and spleen nodes, and no increase in size of other nodes nor any new sites of disease.

Secondary Outcome Measures

1. Percentage of Participants Who Responded (Overall Response Rate - ORR) at Week 12 Based on Independent Central Assessment of Disease [Week 12]

   Overall response within the first treatment cycle was assessed according to International Working Group - Non-Hodgkin Lymphoma criteria (IWG-NHL criteria [Cheson et al, 1999]) by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement), and bone marrow biopsy (to assess bone marrow infiltration). ORR was the percentage of participants with a best overall response of complete response (CR), unconfirmed complete response (CRu) or partial response (PR). Participants that do not meet the criteria for response were considered non-responders. CR was defined as no evidence of disease. CRu showed nodes in the original sum of the products (SPD) regressed by >75% and/or indeterminate bone marrow results. PR was a ≥ 50% decrease in SPD of the six largest dominant nodes; >=50% decrease in liver and spleen nodes, and no increase in size of other nodes nor any new sites of disease.

2. Pharmacokinetic Serum Concentrations by Visit [Weeks 2, 3, 4, 12 and 20]

   Pharmacokinetic serum samples were analyzed by a central lab. Lower limit of quantification (LLOQ) was 0.25 ug/mL. PK concentrations below the lower limit of quantification were assigned a value of 0. Geometric mean and geometric CV were only calculated using concentrations >0.

3. Percentage of Participants With Complete Depletion of Clusters of Differentiation 19-Positive (CD19+) Cell Count From Baseline to Day 8 [Baseline (Day 1), Study Day 8]

   Complete depletion of CD19+ cell count at any postdose time was defined as CD19+ cell counts < 20 cell/μL (0.02 * 10^9 cell/L). Participants with missing CD19+ cell count at baseline or participants with CD19+ cell count < 20 cell/μL at baseline were to be excluded from the derivation of complete depletion of CD19+ cell count.

4. Total Immunoglobulin G (IgG) Results by Visit [Baseline (Day 1), Day 8 (Week 2), Weeks 3, 4, 28]

   Samples were analyzed by a central lab.

5. Total Immunoglobulin M (IgM) Results by Visit [Baseline (Day 1), Day 8 (Week 2), Weeks 3, 4, 28]

   Samples were analyzed by a central lab.

6. Participants With Treatment-Emergent Adverse Events [Day 1 (post treatment) to Week 28]

   An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. Each AE was graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where Grade 1 = Mild AE Grade 2 = Moderate AE Grade 3 = Severe AE Grade 4 = Life-threatening or disabling AE Grade 5 = Death related to AE. Serious adverse events include any event that is fatal, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or other significant medical hazard. IP = investigational product

7. Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs) [Day 1 (post treatment) to Week 28]

   The AEOIs prespecified for this study were infusion reactions including hypersensitivity, cardiac disorders, serious infections, progressive multifocal leukoencephalopathy, hematological reactions, hepatitis B reactivation, opportunistic infections, severe mucocutaneous reactions, tumor lysis syndrome, gastrointestinal perforation, and reversible posterior leukoencephalopathy syndrome. Infusion reactions including hypersensitivity adverse events of interest must have start date the same as, or one day after, an investigational product administration start date.

8. Number of Participants Who Developed Anti-drug Antibodies [Baseline (Day 1), Weeks 12, 20 and 28]

   Samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect antibodies capable of binding to ABP 798/rituximab (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based assay to determine neutralizing activity against ABP 798/rituximab (Neutralizing Antibody Assay). Developing antibody incidence was defined as participants with a negative or no binding antibody result at baseline and a positive antibody result at any post-baseline time point.

9. Participants' Progression-Free Survival (PFS) Status Based on the Independent Central Assessment of Disease [Day 1 up to Week 28]

   PFS was based on disease assessments determined by the central, independent, blinded radiologists' and oncologist's review.

10. Percentage of Participants Who Survived -- Overall Survival (OS) [Day 1 up to Week 28]

    Percentage of participants who were alive at the end of the study.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Males and females 18 years of age and older

• Histological confirmed (by lymph node or extranodal region biopsy), Grade 1, 2, or 3a follicular B-cell NHL expressing CD20 within 12 months before randomization

• Stage 2, 3, or 4 (per Cotswold's Modification of Ann Arbor Staging System) with measurable disease (per International Working Group)

• subjects must have a baseline scan (computed tomography [CT]) of the neck (if palpable lymph node > 1.0 cm), chest, abdomen, and pelvis to assess disease burden within 6 weeks before randomization

• subjects must have had a baseline bone marrow biopsy within 12 months before randomization. Previously confirmed positive bone marrow involvement does not need to be repeated for purposes of screening.

• Low tumor burden based on the Groupe d'Etudes des Lymphomes Folliculaires (GELF) criteria

• largest nodal or extranodal mass ≤ 7 cm

• no more than 3 nodal sites with diameter > 3 cm

• no splenomegaly > 16cm by CT scan and no symptomatic splenomegaly

• no significant pleural or peritoneal serous effusions by CT

• lactate dehydrogenase ≤ upper limit of normal (ULN)

• no B symptoms (night sweats, fever [temperature > 38°C], weight loss > 10% in the previous 6 months)

Exclusion Criteria:

• Diffuse large cell component and/or Grade 3b follicular NHL

• History or known presence of central nervous system metastases

• Malignancy other than NHL within 5 years (except treated in-situ cervical cancer, or squamous or basal cell carcinoma of the skin)

• Recent infection requiring a course of systemic anti-infective agents that was completed ≤ 7 days before randomization (with the exception of uncomplicated urinary tract infection)

• Other investigational procedures that can impact the study data, results, or patient safety while participating in this study are excluded; participation in observational studies is allowed.

• Subject is currently enrolled in or has not yet completed at least 30 days or 5 half-lives (whichever is longer) since ending other investigational device or drug study(s), including vaccines, or subject is receiving other investigational agent(s)

• Previous use of either commercially available or investigational chemotherapy, biological, or immunological therapy for NHL (including rituximab or biosimilar rituximab, or other anti-CD20 treatments)

• Systemic corticosteroid use within 3 months before randomization (inhaled are allowable)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Encinitas	California	United States	92024-1332
2	Research Site	Mount Sterling	Kentucky	United States	40353
3	Research Site	Billings	Montana	United States	59102
4	Research Site	Zanesville	Ohio	United States	43701
5	Research Site	Roanoke	Virginia	United States	24014
6	Research Site	Gosford	New South Wales	Australia	2250
7	Research Site	Frankston	Victoria	Australia	3199
8	Research Site	Perth	Western Australia	Australia	6000
9	Research Site	Plovdiv		Bulgaria	4002
10	Research Site	Stara Zagora		Bulgaria	6000
11	Research Site	Windsor	Ontario	Canada	N8W 2X3
12	Research Site	Medellin	Antioquia	Colombia	050034
13	Research Site	Bogota	Cundinamarca	Colombia	110111
14	Research Site	Praha 5	Praha	Czechia	150 06
15	Research Site	Ostrava - Poruba	Severomoravsky KRAJ	Czechia	708 52
16	Research Site	Bordeaux Cedex	Aquitaine	France	33077
17	Research Site	Clermont Ferrand	Auvergne	France	63050
18	Research Site	Cesson-Sevigne	Bretagne	France	35576
19	Research Site	Boulogne sur Mer	NORD Pas-de-calais	France	62321
20	Research Site	La Rochelle	Poitou-charentes	France	17000
21	Research Site	Poitiers Cedex	Poitou-charentes	France	86021
22	Research Site	Batumi		Georgia	6000
23	Research Site	Tbilisi		Georgia	0112
24	Research Site	Tbilisi		Georgia	0160
25	Research Site	Tbilisi		Georgia	0186
26	Research Site	Freiburg	Baden-wuerttemberg	Germany	79110
27	Research Site	Augsburg	Bayern	Germany	86156
28	Research Site	Würzburg	Bayern	Germany	97080
29	Research Site	Kassel	Hessen	Germany	34125
30	Research Site	Münster	Nordrhein-westfalen	Germany	48149
31	Research Site	Leipzig	Sachsen	Germany	04103
32	Research Site	Flensburg	Schleswig-holstein	Germany	24939
33	Research Site	Athens	Attica	Greece	11525
34	Research Site	Athens	Attica	Greece	11527
35	Research Site	Patra	Peloponnese	Greece	26504
36	Research Site	Surat	Gujarat	India	395010
37	Research Site	Vadodara	Gujarat	India	390001
38	Research Site	Bangalore	Karnataka	India	560068
39	Research Site	Mangalore	Karnataka	India	575001
40	Research Site	Nashik	Maharashtra	India	422004
41	Research Site	Pune	Maharashtra	India	411 001
42	Research Site	Bikaner	Rajasthan	India	334 003
43	Research Site	Be'er Ya'akov	Rehoboth	Israel	7030000
44	Research Site	San Giovanni Rotondo	Foggia	Italy	71013
45	Research Site	Bergamo	Lombardia	Italy	24127
46	Research Site	Pesaro	Pesaro E Urbino	Italy	61100
47	Research Site	Aviano	Pordenone	Italy	33081
48	Research Site	Candiolo	Torino	Italy	10060
49	Research Site	Brescia		Italy	25123
50	Research Site	Milano		Italy	20141
51	Research Site	Milano		Italy	20153
52	Research Site	Padova		Italy	35128
53	Research Site	Parma		Italy	43126
54	Research Site	Ravenna		Italy	48100
55	Research Site	Rimini		Italy	47900
56	Research Site	Terni		Italy	05100
57	Research Site	Chiba-city	Chiba	Japan	260-8717
58	Research Site	Fukuoka-shi	Fukuoka	Japan	811-1395
59	Research Site	Maebashi-city	Gunma	Japan	371-8511
60	Research Site	Kobe-city	Hyogo	Japan	650-0047
61	Research Site	Tsu	MIE	Japan	514-8507
62	Research Site	Utsunomiya City	Tochigi	Japan	320-0834
63	Research Site	Tachikawa-city	Tokyo	Japan	190-0014
64	Research Site	Tokyo		Japan	150-8935
65	Research Site	Seoul	Gyeonggi-do	Korea, Republic of	135-710
66	Research Site	Seoul	Gyeonggi-do	Korea, Republic of	158-710
67	Research Site	Busan	Gyeongsangnam-do	Korea, Republic of	48108
68	Research Site	Jinju-si	Gyeongsangnam-do	Korea, Republic of	52727
69	Research Site	Daegu		Korea, Republic of	41931
70	Research Site	Daegu		Korea, Republic of	42415
71	Research Site	Seoul		Korea, Republic of	03080
72	Research Site	Seoul		Korea, Republic of	03181
73	Research Site	Seoul		Korea, Republic of	03722
74	Research Site	Ulsan		Korea, Republic of	44033
75	Research Site	Mexico City	Distrito Federal	Mexico	01120
76	Research Site	Chihuahua		Mexico	31203
77	Research Site	Legnica	Dolnoslaskie	Poland	59-220
78	Research Site	Toruń	Kujawsko-pomorskie	Poland	87-100
79	Research Site	Kraków	Malopolskie	Poland	31-826
80	Research Site	Gdańsk	Pomorskie	Poland	80-219
81	Research Site	Targu-Mures	Mures	Romania	540042
82	Research Site	Targu-Mures	Mures	Romania	540136
83	Research Site	Timisoara	Timis	Romania	300021
84	Research Site	Bucuresti		Romania	030171
85	Research Site	Sabadell	Barcelona	Spain	08208
86	Research Site	Córdoba	Cordoba	Spain	14004
87	Research Site	Majadahonda	Madrid	Spain	28222
88	Research Site	La Laguna Tenerife	Santa CRUZ DE Tenerife	Spain	38320
89	Research Site	Barcelona		Spain	08003
90	Research Site	Caceres		Spain	10003
91	Research Site	Cadiz		Spain	11009
92	Research Site	Madrid		Spain	28046
93	Research Site	Salamanca		Spain	37007
94	Research Site	Kyiv	Kiev	Ukraine	03115
95	Research Site	Kyiv	Kiev	Ukraine	04112
96	Research Site	Uzhgorod	Transcarpathia	Ukraine	88014
97	Research Site	Chernivtsi		Ukraine	58013
98	Research Site	Dnipropetrovsk		Ukraine	49055

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

• Study Protocol - Jul 17, 2017
• Statistical Analysis Plan - Jan 11, 2016

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02747043
• Other Study ID Numbers: 20130109; 2013-005542-11
• First Posted: Apr 21, 2016
• Last Update Posted: Aug 18, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Amgen: CD20 Positive B-cell Non-Hodgkin Lymphoma; ABP 798
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Rituximab

Study Results

Participant Flow

Recruitment Details	A total of 380 subjects were screened and 256 participants (128 in the ABP 798 treatment group and 128 in the rituximab treatment group) were randomized at 91 centers across 20 countries.
Pre-assignment Detail	Participants were randomized centrally to receive either ABP 798 or rituximab in a 1:1 manner. The randomization was stratified based on geographic region (Europe, Americas, Japan, Asia Pacific - Other) and age group (> 60 years of age, ≤ 60 years of age).

Arm/Group Title	ABP 798	Rituximab
Arm/Group Description	ABP 798 was administered at a dose of 375 mg/m^2 as an intravenous (IV) infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.	Rituximab was administered at a dose of 375 mg/m^2 as an IV infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.
Period Title: Overall Study
STARTED	128	128
Treated	128	126
COMPLETED	118	123
NOT COMPLETED	10	5

Baseline Characteristics

Arm/Group Title	ABP 798	Rituximab	Total
Arm/Group Description	ABP 798 was administered at a dose of 375 mg/m^2 as an intravenous (IV) infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.	Rituximab was administered at a dose of 375 mg/m^2 as an IV infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.	Total of all reporting groups
Overall Participants	128	128	256
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.6 (12.72)	58.2 (12.20)	57.9 (12.45)
Age, Customized (Count of Participants)
<= 60 years	71 55.5%	70 54.7%	141 55.1%
> 60 years	57 44.5%	58 45.3%	115 44.9%
Sex: Female, Male (Count of Participants)
Female	68 53.1%	62 48.4%	130 50.8%
Male	60 46.9%	66 51.6%	126 49.2%
Race/Ethnicity, Customized (Count of Participants)
White	102 79.7%	101 78.9%	203 79.3%
Asian, Non-Japanese	17 13.3%	14 10.9%	31 12.1%
Asian, Japanese	7 5.5%	8 6.3%	15 5.9%
Missing	1 0.8%	2 1.6%	3 1.2%
Other	0 0%	2 1.6%	2 0.8%
American Indian or Alaska Native	1 0.8%	0 0%	1 0.4%
White, Asian-Non-Japanese	0 0%	1 0.8%	1 0.4%
Race/Ethnicity, Customized (Count of Participants)
Not Hispanic or Latino	119 93%	119 93%	238 93%
Hispanic or Latino	8 6.3%	7 5.5%	15 5.9%
Not allowed to collect	1 0.8%	2 1.6%	3 1.2%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	75.29 (19.135)	75.19 (16.981)	75.24 (18.063)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	166.81 (10.737)	167.64 (10.292)	167.22 (10.506)
Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
Grade 0	107 83.6%	110 85.9%	217 84.8%
Grade 1	21 16.4%	18 14.1%	39 15.2%
Region of Enrollment (Count of Participants)
Europe	88 68.8%	86 67.2%	174 68%
Asia Pacific - Other	23 18%	23 18%	46 18%
Americas	10 7.8%	11 8.6%	21 8.2%
Japan	7 5.5%	8 6.3%	15 5.9%
Time Since Original Diagnosis (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	6.31 (16.325)	5.17 (10.181)	5.74 (13.590)
Previous Radiation Treatment (Count of Participants)
Yes	3 2.3%	3 2.3%	6 2.3%
No	125 97.7%	125 97.7%	250 97.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Responded (Overall Response Rate - ORR) by Week 28 Based on Independent Central Assessment of Disease
Description	Overall response within the first treatment cycle was assessed according to International Working Group - Non-Hodgkin Lymphoma criteria (IWG-NHL criteria [Cheson et al, 1999]) by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement), and bone marrow biopsy (to assess bone marrow infiltration). ORR was the percentage of participants with a best overall response of complete response (CR), unconfirmed complete response (CRu) or partial response (PR). Participants that do not meet the criteria for response were considered non-responders. CR was defined as no evidence of disease. CRu showed nodes in the original sum of the products (SPD) regressed by >75% and/or indeterminate bone marrow results. PR was a ≥ 50% decrease in SPD of the six largest dominant nodes; >=50% decrease in liver and spleen nodes, and no increase in size of other nodes nor any new sites of disease.
Time Frame	Post treatment up to Week 28

Outcome Measure Data

Analysis Population Description

The modified full analysis set included all randomized participants with evidence of disease at baseline per the tumor assessment from the central, independent, blinded assessments. Analyses for the modified full analysis set was based on randomized treatment assignment.

Arm/Group Title	ABP 798	Rituximab
Arm/Group Description	ABP 798 was administered at a dose of 375 mg/m^2 as an intravenous (IV) infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.	Rituximab was administered at a dose of 375 mg/m^2 as an IV infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.
Measure Participants	123	124
Number [percentage of participants]	78.0 60.9%	70.2 54.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABP 798, Rituximab
	Comments
	Type of Statistical Test	Equivalence
	Comments	Clinical equivalence of the primary endpoint will first be demonstrated by comparing the 1-sided 95% lower confidence limit of the RD of ORR by week 28 between ABP 798 and rituximab with a noninferiority margin of -15%. If this is successful, the 1-sided upper 95% confidence limit of the RD of ORR by week 28 will be compared with a nonsuperiority margin of +35.5%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	7.7
	Confidence Interval	(2-Sided) 90%; -1.4 to 16.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 2-sided 90% confidence limits of the risk difference (RD) of ORR by week 28 used a generalized linear model adjusted for the stratification factors (geographic region and age group).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ABP 798, Rituximab
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	7.7
	Confidence Interval	(2-Sided) 95%; -3.2 to 18.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants Who Responded (Overall Response Rate - ORR) at Week 12 Based on Independent Central Assessment of Disease
Description	Overall response within the first treatment cycle was assessed according to International Working Group - Non-Hodgkin Lymphoma criteria (IWG-NHL criteria [Cheson et al, 1999]) by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement), and bone marrow biopsy (to assess bone marrow infiltration). ORR was the percentage of participants with a best overall response of complete response (CR), unconfirmed complete response (CRu) or partial response (PR). Participants that do not meet the criteria for response were considered non-responders. CR was defined as no evidence of disease. CRu showed nodes in the original sum of the products (SPD) regressed by >75% and/or indeterminate bone marrow results. PR was a ≥ 50% decrease in SPD of the six largest dominant nodes; >=50% decrease in liver and spleen nodes, and no increase in size of other nodes nor any new sites of disease.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The modified full analysis set included all randomized participants with evidence of disease at baseline per the tumor assessment from the central, independent, blinded assessments. Analyses for the modified full analysis set was based on randomized treatment assignment.

Arm/Group Title	ABP 798	Rituximab
Arm/Group Description	ABP 798 was administered at a dose of 375 mg/m^2 as an intravenous (IV) infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.	Rituximab was administered at a dose of 375 mg/m^2 as an IV infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.
Measure Participants	123	124
Number [percentage of participants]	59.3 46.3%	58.1 45.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABP 798, Rituximab
	Comments	The 2-sided 90% confidence limits of the risk difference (RD) of ORR at week 12 used a generalized linear model adjusted for the stratification factors (geographic region and age group).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 90%; -9.3 to 11.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ABP 798, Rituximab
	Comments	The 2-sided 95% confidence limits of the risk difference (RD) of ORR at week 12 used a generalized linear model adjusted for the stratification factors (geographic region and age group).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; -11.3 to 13.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Pharmacokinetic Serum Concentrations by Visit
Description	Pharmacokinetic serum samples were analyzed by a central lab. Lower limit of quantification (LLOQ) was 0.25 ug/mL. PK concentrations below the lower limit of quantification were assigned a value of 0. Geometric mean and geometric CV were only calculated using concentrations >0.
Time Frame	Weeks 2, 3, 4, 12 and 20

Outcome Measure Data

Analysis Population Description

Safety Analysis Set of participants with available data. Participants with PK concentrations below the lower limit of quantification (LLOQ) were excluded from these analyses.

Arm/Group Title	ABP 798	Rituximab
Arm/Group Description	ABP 798 was administered at a dose of 375 mg/m^2 as an intravenous (IV) infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.	Rituximab was administered at a dose of 375 mg/m^2 as an IV infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.
Measure Participants	128	126
Week 2 (predose)	58.66 (50.4)	58.63 (76.9)
Week 3 (predose)	105.39 (37.8)	108.77 (59.1)
Week 4 (predose)	132.70 (42.6)	140.23 (57.9)
Week 12 (predose)	21.86 (156.1)	20.55 (194.1)
Week 12 (postdose)	207.05 (58.1)	209.14 (66.8)
Week 20 (predose)	13.37 (138.7)	16.45 (115.8)

4. Secondary Outcome

Title	Percentage of Participants With Complete Depletion of Clusters of Differentiation 19-Positive (CD19+) Cell Count From Baseline to Day 8
Description	Complete depletion of CD19+ cell count at any postdose time was defined as CD19+ cell counts < 20 cell/μL (0.02 * 10^9 cell/L). Participants with missing CD19+ cell count at baseline or participants with CD19+ cell count < 20 cell/μL at baseline were to be excluded from the derivation of complete depletion of CD19+ cell count.
Time Frame	Baseline (Day 1), Study Day 8

Outcome Measure Data

Analysis Population Description

Full analysis set of participants with available data. Participants with missing CD19+ cell count at baseline or participants with CD19+ cell count < 20 cell/μL at baseline were to be excluded from the derivation of complete depletion of CD19+ cell count.

Arm/Group Title	ABP 798	Rituximab
Arm/Group Description	ABP 798 was administered at a dose of 375 mg/m^2 as an intravenous (IV) infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.	Rituximab was administered at a dose of 375 mg/m^2 as an IV infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.
Measure Participants	115	116
Number [percentage of participants]	98.3 76.8%	98.3 76.8%

5. Secondary Outcome

Title	Total Immunoglobulin G (IgG) Results by Visit
Description	Samples were analyzed by a central lab.
Time Frame	Baseline (Day 1), Day 8 (Week 2), Weeks 3, 4, 28

Outcome Measure Data

Analysis Population Description

Full analysis set of participants with available data

Arm/Group Title	ABP 798	Rituximab
Arm/Group Description	ABP 798 was administered at a dose of 375 mg/m^2 as an intravenous (IV) infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.	Rituximab was administered at a dose of 375 mg/m^2 as an IV infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.
Measure Participants	128	128
Baseline	9.740 (2.5988)	10.570 (2.5970)
Day 8 (Week 2)	9.790 (2.5719)	10.486 (2.4916)
Week 3	9.545 (2.5933)	10.374 (2.3214)
Week 4	9.744 (2.5805)	10.196 (2.2842)
Week 28	9.846 (2.6316)	10.281 (2.3617)

6. Secondary Outcome

Title	Total Immunoglobulin M (IgM) Results by Visit
Description	Samples were analyzed by a central lab.
Time Frame	Baseline (Day 1), Day 8 (Week 2), Weeks 3, 4, 28

Outcome Measure Data

Analysis Population Description

Full analysis set of participants with available data.

Arm/Group Title	ABP 798	Rituximab
Arm/Group Description	ABP 798 was administered at a dose of 375 mg/m^2 as an intravenous (IV) infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.	Rituximab was administered at a dose of 375 mg/m^2 as an IV infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.
Measure Participants	128	128
Baseline	1.021 (1.0072)	1.247 (3.4018)
Day 8 (Week 2)	1.004 (1.0300)	1.280 (3.7292)
Week 3	1.001 (1.0564)	1.370 (5.0250)
Week 4	0.985 (1.0459)	1.385 (5.3266)
Week 28	0.816 (0.8505)	1.127 (3.6752)

7. Secondary Outcome

Title	Participants With Treatment-Emergent Adverse Events
Description	An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. Each AE was graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where Grade 1 = Mild AE Grade 2 = Moderate AE Grade 3 = Severe AE Grade 4 = Life-threatening or disabling AE Grade 5 = Death related to AE. Serious adverse events include any event that is fatal, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or other significant medical hazard. IP = investigational product
Time Frame	Day 1 (post treatment) to Week 28

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	ABP 798	Rituximab
Arm/Group Description	ABP 798 was administered at a dose of 375 mg/m^2 as an intravenous (IV) infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.	Rituximab was administered at a dose of 375 mg/m^2 as an IV infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.
Measure Participants	128	126
Any AE	107 83.6%	95 74.2%
Any grade >=3 AE	14 10.9%	13 10.2%
Any fatal AE	0 0%	0 0%
Any serious AE	5 3.9%	5 3.9%
Any AE leading to discontinuation of IP	4 3.1%	1 0.8%
Any AE leading to dose delay/withheld IP	9 7%	9 7%

8. Secondary Outcome

Title	Percentage of Participants With Treatment-emergent Adverse Events of Interest (AEOIs)
Description	The AEOIs prespecified for this study were infusion reactions including hypersensitivity, cardiac disorders, serious infections, progressive multifocal leukoencephalopathy, hematological reactions, hepatitis B reactivation, opportunistic infections, severe mucocutaneous reactions, tumor lysis syndrome, gastrointestinal perforation, and reversible posterior leukoencephalopathy syndrome. Infusion reactions including hypersensitivity adverse events of interest must have start date the same as, or one day after, an investigational product administration start date.
Time Frame	Day 1 (post treatment) to Week 28

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title	ABP 798	Rituximab
Arm/Group Description	ABP 798 was administered at a dose of 375 mg/m^2 as an intravenous (IV) infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.	Rituximab was administered at a dose of 375 mg/m^2 as an IV infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.
Measure Participants	128	126
Any AEOI	49.2 38.4%	45.2 35.3%
Infusion reactions including hypersensitivity	43.0 33.6%	42.9 33.5%
Hematological reactions	5.5 4.3%	4.8 3.8%
Cardiac disorders	2.3 1.8%	1.6 1.3%
Serious infections	1.6 1.3%	0 0%
Severe mucocutaneous reactions	0.8 0.6%	0 0%
Gastrointestinal perforation	0 0%	0 0%
Hepatitis B reactivation	0 0%	0 0%
Opportunistic infection	0 0%	0 0%
Progressive multifocal leukoencephalopathy	0 0%	0 0%
Reversible posterior leukoencephalopathy	0 0%	0 0%
Tumor lysis syndrome	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABP 798, Rituximab
	Comments	Percentage risk difference for 'Any adverse event of interest'
	Type of Statistical Test	Other
	Comments	Risk difference (ABP 798 - Rituximab) and CIs were estimated by Wald asymptotic confidence limits, or exact confidence limits if n < 25 for either treatment.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	4.0
	Confidence Interval	(2-Sided) 95%; -8.3 to 16.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ABP 798, Rituximab
	Comments	Percentage risk difference for 'Infusion reactions including hypersensitivity'
	Type of Statistical Test	Other
	Comments	Risk difference (ABP 798 - Rituximab) and CIs were estimated by Wald asymptotic confidence limits, or exact confidence limits if n < 25 for either treatment.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -12.1 to 12.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ABP 798, Rituximab
	Comments	Percentage risk difference for 'Hematological reactions'
	Type of Statistical Test	Other
	Comments	Risk difference (ABP 798 - Rituximab) and CIs were estimated by Wald asymptotic confidence limits, or exact confidence limits if n < 25 for either treatment.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -11.8 to 13.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	ABP 798, Rituximab
	Comments	Percentage risk difference in 'Cardiac disorders'
	Type of Statistical Test	Other
	Comments	Risk difference (ABP 798 - Rituximab) and CIs were estimated by Wald asymptotic confidence limits, or exact confidence limits if n < 25 for either treatment.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; -11.8 to 13.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ABP 798, Rituximab
	Comments	Percentage risk difference in 'Serious infections'
	Type of Statistical Test	Other
	Comments	Risk difference (ABP 798 - Rituximab) and CIs were estimated by Wald asymptotic confidence limits, or exact confidence limits if n < 25 for either treatment.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95%; -10.9 to 14.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	ABP 798, Rituximab
	Comments	Percentage risk difference in 'Severe mucocutaneous reactions'
	Type of Statistical Test	Other
	Comments	Risk difference (ABP 798 - Rituximab) and CIs were estimated by Wald asymptotic confidence limits, or exact confidence limits if n < 25 for either treatment.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; -11.7 to 13.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Number of Participants Who Developed Anti-drug Antibodies
Description	Samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect antibodies capable of binding to ABP 798/rituximab (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based assay to determine neutralizing activity against ABP 798/rituximab (Neutralizing Antibody Assay). Developing antibody incidence was defined as participants with a negative or no binding antibody result at baseline and a positive antibody result at any post-baseline time point.
Time Frame	Baseline (Day 1), Weeks 12, 20 and 28

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	ABP 798	Rituximab
Arm/Group Description	ABP 798 was administered at a dose of 375 mg/m^2 as an intravenous (IV) infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.	Rituximab was administered at a dose of 375 mg/m^2 as an IV infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.
Measure Participants	126	123
Binding antibody positive	3 2.3%	1 0.8%
Neutralizing antibody positive	1 0.8%	1 0.8%

10. Secondary Outcome

Title	Participants' Progression-Free Survival (PFS) Status Based on the Independent Central Assessment of Disease
Description	PFS was based on disease assessments determined by the central, independent, blinded radiologists' and oncologist's review.
Time Frame	Day 1 up to Week 28

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	ABP 798	Rituximab
Arm/Group Description	ABP 798 was administered at a dose of 375 mg/m^2 as an intravenous (IV) infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.	Rituximab was administered at a dose of 375 mg/m^2 as an IV infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.
Measure Participants	128	126
Participants with disease progression or death	3.1 2.4%	2.4 1.9%
Participants alive and progression-free	96.9 75.7%	97.6 76.3%

11. Secondary Outcome

Title	Percentage of Participants Who Survived -- Overall Survival (OS)
Description	Percentage of participants who were alive at the end of the study.
Time Frame	Day 1 up to Week 28

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	ABP 798	Rituximab
Arm/Group Description	ABP 798 was administered at a dose of 375 mg/m^2 as an intravenous (IV) infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.	Rituximab was administered at a dose of 375 mg/m^2 as an IV infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.
Measure Participants	128	126
Number [percentage of participants]	100 78.1%	100 78.1%

Adverse Events

Time Frame	Day 1 to 28 weeks
Adverse Event Reporting Description	Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Arm/Group Title	ABP 798		Rituximab
Arm/Group Description	ABP 798 was administered at a dose of 375 mg/m^2 as an intravenous (IV) infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.		Rituximab was administered at a dose of 375 mg/m^2 as an IV infusion once weekly for 4 weeks followed by dosing at weeks 12 and 20.
All Cause Mortality
	ABP 798		Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/128 (0%)		0/126 (0%)
Serious Adverse Events
	ABP 798		Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/128 (3.9%)		5/126 (4%)
Cardiac disorders
Coronary artery stenosis	0/128 (0%)		1/126 (0.8%)
Gastrointestinal disorders
Abdominal pain	0/128 (0%)		1/126 (0.8%)
Colitis ulcerative	0/128 (0%)		1/126 (0.8%)
Dysphagia	0/128 (0%)		1/126 (0.8%)
Stomatitis	1/128 (0.8%)		0/126 (0%)
General disorders
Chills	0/128 (0%)		1/126 (0.8%)
Pyrexia	1/128 (0.8%)		0/126 (0%)
Infections and infestations
Lower respiratory tract infection	1/128 (0.8%)		0/126 (0%)
Septic shock	1/128 (0.8%)		0/126 (0%)
Viral infection	1/128 (0.8%)		0/126 (0%)
Injury, poisoning and procedural complications
Hip fracture	1/128 (0.8%)		0/126 (0%)
Limb traumatic amputation	1/128 (0.8%)		0/126 (0%)
Nervous system disorders
Headache	0/128 (0%)		1/126 (0.8%)
Reproductive system and breast disorders
Erectile dysfunction	0/128 (0%)		1/126 (0.8%)
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	0/128 (0%)		1/126 (0.8%)
Other (Not Including Serious) Adverse Events
	ABP 798		Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/128 (46.1%)		61/126 (48.4%)
Gastrointestinal disorders
Abdominal pain	4/128 (3.1%)		9/126 (7.1%)
Diarrhoea	3/128 (2.3%)		9/126 (7.1%)
Nausea	6/128 (4.7%)		14/126 (11.1%)
General disorders
Asthenia	12/128 (9.4%)		6/126 (4.8%)
Fatigue	13/128 (10.2%)		12/126 (9.5%)
Pyrexia	8/128 (6.3%)		8/126 (6.3%)
Infections and infestations
Upper respiratory tract infection	7/128 (5.5%)		1/126 (0.8%)
Nervous system disorders
Headache	15/128 (11.7%)		12/126 (9.5%)
Respiratory, thoracic and mediastinal disorders
Throat irritation	9/128 (7%)		8/126 (6.3%)
Skin and subcutaneous tissue disorders
Pruritus	6/128 (4.7%)		12/126 (9.5%)
Rash	9/128 (7%)		6/126 (4.8%)
Urticaria	7/128 (5.5%)		2/126 (1.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.