HOMER: Single Agent Ofatumumab Vs. Single Agent Rituximab in Indolent B-Cell Non Hodgkin Lymphoma Relapsed After Rituximab-Containing Therapy

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01200589
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 438
• Locations: 155
• Arms: 2
• Actual Duration (Months): 74.3
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This was a multi-center, parallel, active comparator controlled, open-label, randomized (1:1) phase III study of single agent ofatumumab compared to single agent rituximab in subjects with rituximab-sensitive indolent B-cell non hodgkin lymphoma that has relapsed at least 6 months after completing treatment with single agent rituximab or a rituximab-containing regimen. Subjects must have attained a Complete Response or Partial Response to their last prior rituximab containing therapy lasting at least six months beyond the end of rituximab therapy. Subjects were to receive four weekly doses of single agent ofatumumab (1000 mg) or rituximab (375 mg/m2), followed by ofatumumab (1000 mg) or rituximab (375 mg/m2) every 2 months for four additional doses. Therefore, subjects were to receive a total of eight doses of anti-CD20 antibody over 9 months. Subjects were evaluated for response after completion of the first four doses of therapy, after six doses of therapy, and after completion of study therapy. Subjects were to be followed until the end of the designated follow-up period (total study duration of 200 weeks) or until they meet the withdrawal criteria.

The primary objective of the study OMB157D 2303 was to demonstrate the efficacy of Arzerra based on the primary endpoint (Progression-free survival (PFS) as assessed by the IRC) in patients with Indolent B-cell Non-Hodgkin's Lymphoma Relapsed After Rituximab-Containing Regimen.

The Independent Data Monitoring Committee (IDMC) met on November 22, 2015 and recommended the termination of the study due to futility (cut-off date = 12Jun2015). The IDMC reviewed analyses results for progression free survival (PFS), overall response rate (ORR), and overall survival (OS). Novartis accepted this recommendation and the study was closed.

Final analysis was performed (cut-off date =19 Dec 2016). As the study was stopped for futility, the primary objective was not met and some secondary endpoints, supportive of primary objective (Duration of Response (DOR), time to next therapy, and pharmacokinetics) were removed as secondary end points.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma	Biological: Ofatumumab; Biological: Rituximab; Biological: Ofatumumab; Biological: Rituximab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 438 participants
• Allocation: Randomized
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase III Randomized, Open Label Study of Single Agent Ofatumumab Vs. Single Agent Rituximab in Indolent B-Cell Non Hodgkin Lymphoma Relapsed After Rituximab-Containing Therapy
• Actual Study Start Date: Oct 11, 2010
• Actual Primary Completion Date: Dec 19, 2016
• Actual Study Completion Date: Dec 19, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Ofatumumab Four weekly doses of single agent ofatumumab (1000 mg), followed by ofatumumab (1000 mg) every two months for four additional doses.	Biological: Ofatumumab; liquid concentrate for solution for infusion in glass vials containing 50 mL of solution at a concentration of 20mg/ml to provide 1000 mg per vial.; Other Names: Arzerra ; Biological: Ofatumumab; Four weekly doses of single agent ofatumumab (1000 mg), followed by ofatumumab (1000 mg) every two months for four additional doses.; Other Names: Arzerra
Active Comparator: Arm B: Rituximab Four weekly doses of single agent rituximab (375 mg/m2), followed by rituximab (375 mg/m2) every two months for four additional doses.	Biological: Rituximab; sourced locally from commercial stock; Other Names: Mabthera Rituxan ; Biological: Rituximab; Four weekly doses of single agent rituximab (375 mg/m2), followed by rituximab (375 mg/m2) every two months for four additional doses.; Other Names: Mabthera Rituxan

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) - Number of Participants With PFS Events [200 weeks]

   Disease response assessed by modified 2007 Revised Response Criteria for Malignant Lymphoma. Nodal disease, PD: 1)prev. normal node (<=1.5cm x <=1.0cm) that incr. to >2.0 x ≥1.5cm; 2)≥50% incr. from nadir product of perpendicular diameter (PPD) of any prev. involved node with long axis >1.5cm at baseline (BL) (must incr. by ≥0.5mm & to >2.0cm) OR ≥50% incr. from nadir in long axis of any prev. inv. node with long axis of >1.5cm at BL (long axis must incr. by ≥0.5mm & to >2.0cm); or 3)≥50% incr. from nadir in the sums of prod. of diameters (SPD) of target nodes & ≥1 node with long axis >1.5cm. Extranodal, PD 1)any new lesion >2.0 x ≥1.5cm not attributed to non-lymphoma causes; 2)≥50% incr. from nadir PPD of any targ. les. & >5mm incr. in either axis & les. must measure >1.5cm x ≥1.5cm OR ≥50% incr. from nadir in long axis of any targ. les. & >5mm incr. in either axis & les. must measure >1.5cm x ≥1.5cm; or 3)≥50% incr. from nadir in SPD of targ. nodes & ≥1 node with long axis >1.5cm.

Secondary Outcome Measures

1. Number of Participants With Complete Response (CR) [200 weeks]

   Complete response was assessed according to modified 2007 Revised Response Criteria for Malignant Lymphoma (RRCML) and defined as follows: 1) complete disappearance of all detectable clinical evidence of disease (all target nodes regressing to <=1.5cm in the long axis and all non-target lesions being normal in size by imaging) and disease-related symptoms if present before therapy; 2) the spleen/liver, if considered enlarged due to lymphoma based on CT scan prior to therapy, would be normal and nodules should disappear; and 3) if bone marrow was involved before treatment, the infiltrate must clear on repeat bone marrow biopsy. Computed tomography (CT) scans of the neck, thorax, abdomen and pelvis were performed as part of the efficacy evaluation.

2. Number of Participants With Overall Response (OR) [200 weeks]

   The overall response rate (ORR) was defined as the number of participants achieving a CR or partial response (PR). from start of randomization until disease progression, or the start of a new anti-cancer therapy. Disease response was assessed according to modified 2007 Revised Response Criteria for Malignant Lymphoma (RRCML). Computed tomography (CT) scans of the neck, thorax, abdomen and pelvis were performed as part of the efficacy evaluation. Bone marrow examination to confirm a suspected complete response (CR) was performed within 8 weeks following the onset of a CT scan confirmed CR.

3. Number of Deaths [200 weeks]

   The number of deaths were assessed.

4. Number of Participants With Infection Related Adverse Events [200 weeks]

   The number of participants with infection related adverse events was assessed.

5. Number of Participants With Infusion Related Adverse Events Due to Study Drug [36 weeks + 60 days]

   The number of participants with infusion related adverse events due to study drug was assessed.

6. Number of Participants With Myelosuppression Adverse Events [200 weeks]

   The number of participants with myelosuppression adverse events was assessed.

7. Duration of Response (DOR) [200 weeks]

8. Time to Next Treatment [200 weeks]

9. Pharmacokinetics [70 weeks]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Indolent NHL subtypes defined according to World Health Organization guidelines:

2. Follicular lymphoma Grades 1, 2, 3 A

3. Small lymphocytic lymphoma (SLL)

4. Marginal zone lymphoma

5. Lymphoplasmacytic lymphoma

6. Rituximab-sensitive iNHL, defined as a partial or complete response to their last prior treatment with rituximab or a rituximab-containing regimen lasting at least 6 months following completion of rituximab treatment.

7. Relapse or disease progression following response to prior rituximab-based therapy, as defined by 2007 RRCML criteria, which requires therapy.

8. Radiographically measurable disease, defined as: 2 or more clearly demarcated lesions/nodes with a long axis >1.5 cm and short axis ≥1.0cm. OR 1 clearly demarcated lesion/node with a long axis >2.0 cm and short axis ≥1.0cm.

9. ECOG Performance Status of 0, 1, or 2.

10. Age ≥18 years.

11. Life expectancy of at least 6 months in the opinion of the investigator.

12. The patient or their legally acceptable representative must be capable of giving written informed consent prior to performing any study-specific tests or procedures.

13. All prior treatment related non-hematologic toxicities (with the exception of alopecia) must have resolved to CTCAE (Version 4.0) ≤ Grade 2 at the time of randomization.

14. One or more of the following indications for treatment:

15. Cytopenias

16. One or more of the following lymphoma-related symptoms:

• Night sweats without signs of infection

• Unintentional weight loss (10% within the previous 6 months)

• Recurrent, unexplained fever of greater than 100.5F (38C) without signs of infection

• Fatigue which interferes with the patient's quality of life

1. Progressive or massive lymphadenopathy OR

2. Progressive or massive organomegaly French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

1. Previous treatment with ofatumumab.

2. Previous anti-CD20 radioimmunotherapy (RIT) or non-rituximab anti-CD20 therapy (such as obinutuzumab) within 6 months prior to randomization. Patients who have received previous anti-CD20 RIT or non-rituximab anti-CD20 therapy (such as obinutuzumab) must have attained a partial or complete response lasting at least 6 months, and must have recovered from any hematologic or other toxicity.

3. Previous autologous stem cell transplantation within 6 months prior to randomization.

4. Previous allogeneic stem cell transplantation.

5. Previous anti-lymphoma monoclonal antibody therapy (excluding anti-CD20 therapy and anti-CD20 RIT), chemotherapy, glucocorticoid, or other systemic therapy for lymphoma within 3 months prior to randomization.

6. Current or previous participation in the treatment phase of another interventional clinical study within 4 weeks prior to randomization. Patients may continue in the follow-up phase of another interventional clinical study, but may not have undergone any treatment on the other study within 4 weeks prior to randomization.

7. Current or previous other malignancy within 2 years prior to randomization. Subjects who have been free of malignancy for at least 2 years, or have a history of completely resected non-melanoma skin cancer or successfully treated carcinoma in situ, are eligible.

8. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, active Hepatitis C, and known HIV disease. All HIV-positive patients are excluded from this study, regardless of whether they have an Acquired Immunodeficiency Syndrome (AIDS) defining disease and/or are on antiviral therapy. Prophylactic antiviral and/or antibacterial antibiotics to prevent recurrence of previous infections are permitted.

9. Clinically significant cardiac disease as judged by the investigator including unstable angina, acute myocardial infarction within 6 months prior to randomization, uncontrolled congestive heart failure, and uncontrolled arrhythmia. Subjects with congestive heart disease or arrhythmias such as atrial fibrillation whose cardiac disease is well controlled on a stable medical regimen are eligible.

10. Other significant concurrent, uncontrolled medical conditions including, but not limited to, renal, hepatic, autoimmune, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which, in the investigator's opinion, will impact study participation.

11. Screening laboratory values:

12. Neutrophils < 1.5 x 10^9/L (unless due to iNHL involvement of the bone marrow)

13. Platelets < 50 x 10^9/L (unless due to iNHL involvement of the bone marrow)

14. ALT or AST > 3 x ULN

15. Alkaline phosphatase > 1.5 x ULN (unless due to lymphoma or a non-malignant, non-hepatic cause such as Paget's disease)

16. Total bilirubin > 1.5 x ULN (unless due to lymphoma or isolated, predominantly indirect hyperbilirubinemia due to Gilbert's syndrome)

17. Known or suspected inability to fully comply with study protocol

18. Because the effects of ofatumumab on fetuses and nursing infants are not known, the following are ineligible for study entry:

19. Lactating women.

20. Women with a positive pregnancy test at study entry.

21. Men with partners of childbearing potential and women of childbearing potential who are not willing to use adequate contraception from study entry through one year following last treatment dose. (Adequate contraception is defined as abstinence, oral hormonal birth control, hormonal birth control injections, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device, and male partner sterilization if male partner is the sole partner for a female subject. The double barrier method can be used in regions where considered acceptable and adequate, defined as condom or occlusive cap plus spermicidal agent).

22. Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones).

23. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Anchorage	Alaska	United States	99508
2	Novartis Investigative Site	Gilbert	Arizona	United States	85234
3	Novartis Investigative Site	Hot Springs	Arkansas	United States	71913
4	Novartis Investigative Site	Greenbrae	California	United States	94904
5	Novartis Investigative Site	Monterey	California	United States	93940
6	Novartis Investigative Site	Pleasant Hill	California	United States	94523
7	Novartis Investigative Site	Rancho Mirage	California	United States	92270
8	Novartis Investigative Site	Salinas	California	United States	93901
9	Novartis Investigative Site	San Diego	California	United States	92123
10	Novartis Investigative Site	San Pablo	California	United States	94806
11	Novartis Investigative Site	Santa Monica	California	United States	90403
12	Novartis Investigative Site	New Milford	Connecticut	United States	06776
13	Novartis Investigative Site	Torrington	Connecticut	United States	06790
14	Novartis Investigative Site	Lakeland	Florida	United States	33805
15	Novartis Investigative Site	Orlando	Florida	United States	32806
16	Novartis Investigative Site	Pembroke Pines	Florida	United States	33028
17	Novartis Investigative Site	Port Saint Lucie	Florida	United States	34952
18	Novartis Investigative Site	West Palm Beach	Florida	United States	33401
19	Novartis Investigative Site	Macon	Georgia	United States	31201-8300
20	Novartis Investigative Site	Marietta	Georgia	United States	30060
21	Novartis Investigative Site	Evanston	Illinois	United States	60201
22	Novartis Investigative Site	Peoria	Illinois	United States	61615
23	Novartis Investigative Site	Quincy	Illinois	United States	62301
24	Novartis Investigative Site	Skokie	Illinois	United States	60076
25	Novartis Investigative Site	Anderson	Indiana	United States	46016
26	Novartis Investigative Site	Indianapolis	Indiana	United States	46237
27	Novartis Investigative Site	Ames	Iowa	United States	50010
28	Novartis Investigative Site	Mount Sterling	Kentucky	United States	40353
29	Novartis Investigative Site	Metairie	Louisiana	United States	70006
30	Novartis Investigative Site	Shreveport	Louisiana	United States	71103
31	Novartis Investigative Site	Waterville	Maine	United States	04901
32	Novartis Investigative Site	Silver Spring	Maryland	United States	20910
33	Novartis Investigative Site	Grand Rapids	Michigan	United States	49503
34	Novartis Investigative Site	Kalamazoo	Michigan	United States	49007
35	Novartis Investigative Site	Jackson	Mississippi	United States	39202
36	Novartis Investigative Site	Columbia	Missouri	United States	65201
37	Novartis Investigative Site	Kansas City	Missouri	United States	64111
38	Novartis Investigative Site	Saint Joseph	Missouri	United States	64507
39	Novartis Investigative Site	Springfield	Missouri	United States	65807
40	Novartis Investigative Site	Bozeman	Montana	United States	59715
41	Novartis Investigative Site	Lincoln	Nebraska	United States	68506
42	Novartis Investigative Site	Lincoln	Nebraska	United States	68510
43	Novartis Investigative Site	Albuquerque	New Mexico	United States	87110
44	Novartis Investigative Site	Albuquerque	New Mexico	United States	87131
45	Novartis Investigative Site	Lake Success	New York	United States	10042
46	Novartis Investigative Site	Mount Kisco	New York	United States	10549
47	Novartis Investigative Site	Greensboro	North Carolina	United States	27403
48	Novartis Investigative Site	Bismarck	North Dakota	United States	58501
49	Novartis Investigative Site	Canton	Ohio	United States	44708
50	Novartis Investigative Site	Canton	Ohio	United States	44710
51	Novartis Investigative Site	Portland	Oregon	United States	97213
52	Novartis Investigative Site	Danville	Pennsylvania	United States	17822
53	Novartis Investigative Site	Ephrata	Pennsylvania	United States	17522
54	Novartis Investigative Site	Lancaster	Pennsylvania	United States	17605
55	Novartis Investigative Site	Willow Grove	Pennsylvania	United States	19090
56	Novartis Investigative Site	Chattanooga	Tennessee	United States	37404
57	Novartis Investigative Site	Germantown	Tennessee	United States	38138
58	Novartis Investigative Site	Knoxville	Tennessee	United States	37916
59	Novartis Investigative Site	Fort Sam Houston	Texas	United States	78234
60	Novartis Investigative Site	Houston	Texas	United States	77030
61	Novartis Investigative Site	Ogden	Utah	United States	84403
62	Novartis Investigative Site	Salt Lake City	Utah	United States	84106
63	Novartis Investigative Site	Fredericksburg	Virginia	United States	22408
64	Novartis Investigative Site	Kennewick	Washington	United States	99336
65	Novartis Investigative Site	Kirkland	Washington	United States	98034
66	Novartis Investigative Site	Mount Vernon	Washington	United States	98273
67	Novartis Investigative Site	Seattle	Washington	United States	98109
68	Novartis Investigative Site	Seattle	Washington	United States	98112
69	Novartis Investigative Site	Sequim	Washington	United States	98382
70	Novartis Investigative Site	Spokane	Washington	United States	99208
71	Novartis Investigative Site	Antwerpen		Belgium	2020
72	Novartis Investigative Site	Antwerpen		Belgium	2060
73	Novartis Investigative Site	Brugge		Belgium	8000
74	Novartis Investigative Site	Brussels		Belgium	1090
75	Novartis Investigative Site	Bruxelles		Belgium	1000
76	Novartis Investigative Site	Kortrijk		Belgium	8500
77	Novartis Investigative Site	Leuven		Belgium	3000
78	Novartis Investigative Site	Wilrijk		Belgium	2610
79	Novartis Investigative Site	Salvador	Bahía	Brazil	41253-190
80	Novartis Investigative Site	Betim	Minas Gerais	Brazil	32.651-760
81	Novartis Investigative Site	Curitiba	Paraná	Brazil	80060-900
82	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul	Brazil	90470-340
83	Novartis Investigative Site	Barretos	São Paulo	Brazil	14784-400
84	Novartis Investigative Site	Jau	São Paulo	Brazil	17210-080
85	Novartis Investigative Site	Sao Paulo	São Paulo	Brazil	01223-001
86	Novartis Investigative Site	Sao Paulo	São Paulo	Brazil	01308-000
87	Novartis Investigative Site	Sao Paulo	São Paulo	Brazil	04039-901
88	Novartis Investigative Site	Sao Paulo	São Paulo	Brazil	05403-000
89	Novartis Investigative Site	Rio de Janeiro		Brazil	20230 -130
90	Novartis Investigative Site	Rio de Janeiro		Brazil	22793-080
91	Novartis Investigative Site	Pleven		Bulgaria	5800
92	Novartis Investigative Site	Plovdiv		Bulgaria	4000
93	Novartis Investigative Site	Sofia		Bulgaria	1233
94	Novartis Investigative Site	Sofia		Bulgaria	1431
95	Novartis Investigative Site	Sofia		Bulgaria
96	Novartis Investigative Site	Varna		Bulgaria	9010
97	Novartis Investigative Site	Moncton	New Brunswick	Canada	E1C 6Z8
98	Novartis Investigative Site	Kitchener	Ontario	Canada	N2G 1G3
99	Novartis Investigative Site	Sherbrooke	Quebec	Canada	J1H 5N4
100	Novartis Investigative Site	Quebec		Canada	G1J 1Z4
101	Novartis Investigative Site	Guangzhou	Guangdong	China	510060
102	Novartis Investigative Site	Guangzhou	Guangdong	China	510080
103	Novartis Investigative Site	Hangzhou	Zhejiang	China	310003
104	Novartis Investigative Site	Beijing		China	100021
105	Novartis Investigative Site	Beijing		China	100044
106	Novartis Investigative Site	Beijing		China	100071
107	Novartis Investigative Site	Beijing		China	100142
108	Novartis Investigative Site	Beijing		China	100730
109	Novartis Investigative Site	Shanghai		China	200025
110	Novartis Investigative Site	Shanghai		China	200032
111	Novartis Investigative Site	Tianjin		China	300020
112	Novartis Investigative Site	Brno		Czechia	625 00
113	Novartis Investigative Site	Hradec Kralove		Czechia
114	Novartis Investigative Site	Ostrava		Czechia	708 52
115	Novartis Investigative Site	Praha 2		Czechia	128 08
116	Novartis Investigative Site	Boulogne sur Mer Cedex		France	62321
117	Novartis Investigative Site	Clermont-Ferrand Cedex 1		France	63003
118	Novartis Investigative Site	La Roche sur Yon Cedex 9		France	85925
119	Novartis Investigative Site	Le Mans		France	72015
120	Novartis Investigative Site	Montpellier cedex 5		France	34295
121	Novartis Investigative Site	Pessac cedex		France	33604
122	Novartis Investigative Site	Budapest		Hungary	1122
123	Novartis Investigative Site	Debrecen		Hungary	4012
124	Novartis Investigative Site	Gyor		Hungary	9023
125	Novartis Investigative Site	Szeged		Hungary	6720
126	Novartis Investigative Site	Aichi		Japan	466-8650
127	Novartis Investigative Site	Kyoto		Japan	602-8566
128	Novartis Investigative Site	Miyagi		Japan	980-8574
129	Novartis Investigative Site	Nagasaki		Japan	852-8501
130	Novartis Investigative Site	Saitama		Japan	350-8550
131	Novartis Investigative Site	Tochigi		Japan	329-0498
132	Novartis Investigative Site	Tokyo		Japan	104-0045
133	Novartis Investigative Site	Tokyo		Japan	135-8550
134	Novartis Investigative Site	Busan		Korea, Republic of	602-715
135	Novartis Investigative Site	Seoul		Korea, Republic of	120-752
136	Novartis Investigative Site	Seoul		Korea, Republic of	135-710
137	Novartis Investigative Site	Miraflores	Lima	Peru	Lima 18
138	Novartis Investigative Site	San Isidro	Lima	Peru	Lima 27
139	Novartis Investigative Site	Lima		Peru	Lima 11
140	Novartis Investigative Site	Lima		Peru	Lima 34
141	Novartis Investigative Site	Lima		Peru	Lima 41
142	Novartis Investigative Site	San Juan		Puerto Rico	00918
143	Novartis Investigative Site	Bratislava		Slovakia	833 10
144	Novartis Investigative Site	Kosice		Slovakia	041 66
145	Novartis Investigative Site	Martin		Slovakia	036 59
146	Novartis Investigative Site	Parktown	Gauteng	South Africa	2193
147	Novartis Investigative Site	Athlone Park, Amanzimtoti		South Africa	4126
148	Novartis Investigative Site	Port Elizabeth		South Africa	6045
149	Novartis Investigative Site	Saxonwold, Johannesburg		South Africa	2196
150	Novartis Investigative Site	Donetsk		Ukraine	83045
151	Novartis Investigative Site	Kyiv		Ukraine	03022
152	Novartis Investigative Site	Kyiv		Ukraine	03115
153	Novartis Investigative Site	Lviv		Ukraine	79044
154	Novartis Investigative Site	Makiivka		Ukraine	86132
155	Novartis Investigative Site	Simferopil		Ukraine	95023

Sponsors and Collaborators

• Novartis Pharmaceuticals
• GlaxoSmithKline

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01200589
• Other Study ID Numbers: 113676
• First Posted: Sep 13, 2010
• Last Update Posted: May 16, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Novartis Pharmaceuticals: Randomized trial; Ofatumumab; Rituximab; Indolent B-Cell Non Hodgkin Lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Rituximab; Ofatumumab; Antibodies, Monoclonal

Study Results

Participant Flow

Pre-assignment Detail	Participants were randomized in a 1:1 ratio to Ofatumumab or Rituximab.

Arm/Group Title	Ofatumumab	Rituximab
Arm/Group Description	Four weekly doses of single agent ofatumumab 1000 mg by intravenous (i.v.) infusion, followed by ofatumumab 1000 mg i.v. every two months for four additional doses.	Four weekly doses of single agent rituximab 375 mg/m2 i.v., followed by rituximab 375 mg/m2 i.v. every two months for four additional doses.
Period Title: Overall Study
STARTED	219	219
Intent-to-treat (ITT) Analysis Set	219	219
Safety Set	217	218
COMPLETED	29	30
NOT COMPLETED	190	189

Baseline Characteristics

Arm/Group Title	Ofatumumab	Rituximab	Total
Arm/Group Description	Four weekly doses of single agent ofatumumab 1000 mg by intravenous (i.v.) infusion, followed by ofatumumab 1000 mg i.v. every two months for four additional doses.	Four weekly doses of single agent rituximab 375 mg/m2 i.v., followed by rituximab 375 mg/m2 i.v. every two months for four additional doses.	Total of all reporting groups
Overall Participants	219	219	438
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.8 (11.27)	60.7 (11.84)	60.8 (11.54)
Sex: Female, Male (Count of Participants)
Female	115 52.5%	109 49.8%	224 51.1%
Male	104 47.5%	110 50.2%	214 48.9%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS) - Number of Participants With PFS Events
Description	Disease response assessed by modified 2007 Revised Response Criteria for Malignant Lymphoma. Nodal disease, PD: 1)prev. normal node (<=1.5cm x <=1.0cm) that incr. to >2.0 x ≥1.5cm; 2)≥50% incr. from nadir product of perpendicular diameter (PPD) of any prev. involved node with long axis >1.5cm at baseline (BL) (must incr. by ≥0.5mm & to >2.0cm) OR ≥50% incr. from nadir in long axis of any prev. inv. node with long axis of >1.5cm at BL (long axis must incr. by ≥0.5mm & to >2.0cm); or 3)≥50% incr. from nadir in the sums of prod. of diameters (SPD) of target nodes & ≥1 node with long axis >1.5cm. Extranodal, PD 1)any new lesion >2.0 x ≥1.5cm not attributed to non-lymphoma causes; 2)≥50% incr. from nadir PPD of any targ. les. & >5mm incr. in either axis & les. must measure >1.5cm x ≥1.5cm OR ≥50% incr. from nadir in long axis of any targ. les. & >5mm incr. in either axis & les. must measure >1.5cm x ≥1.5cm; or 3)≥50% incr. from nadir in SPD of targ. nodes & ≥1 node with long axis >1.5cm.
Time Frame	200 weeks

Outcome Measure Data

Analysis Population Description

The Intent-to-treat (ITT) analysis set, comprised of all randomized participants, was analyzed.

Arm/Group Title	Ofatumumab	Rituximab
Arm/Group Description	Four weekly doses of single agent ofatumumab 1000 mg by intravenous (i.v.) infusion, followed by ofatumumab 1000 mg i.v. every two months for four additional doses.	Four weekly doses of single agent rituximab 375 mg/m2 i.v., followed by rituximab 375 mg/m2 i.v. every two months for four additional doses.
Measure Participants	219	219
Number [Participants]	114 52.1%	117 53.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ofatumumab, Rituximab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants With Complete Response (CR)
Description	Complete response was assessed according to modified 2007 Revised Response Criteria for Malignant Lymphoma (RRCML) and defined as follows: 1) complete disappearance of all detectable clinical evidence of disease (all target nodes regressing to <=1.5cm in the long axis and all non-target lesions being normal in size by imaging) and disease-related symptoms if present before therapy; 2) the spleen/liver, if considered enlarged due to lymphoma based on CT scan prior to therapy, would be normal and nodules should disappear; and 3) if bone marrow was involved before treatment, the infiltrate must clear on repeat bone marrow biopsy. Computed tomography (CT) scans of the neck, thorax, abdomen and pelvis were performed as part of the efficacy evaluation.
Time Frame	200 weeks

Outcome Measure Data

Analysis Population Description

The Intent-to-treat (ITT) analysis set, comprised of all randomized participants, was analyzed.

Arm/Group Title	Ofatumumab	Rituximab
Arm/Group Description	Four weekly doses of single agent ofatumumab 1000 mg by intravenous (i.v.) infusion, followed by ofatumumab 1000 mg i.v. every two months for four additional doses.	Four weekly doses of single agent rituximab 375 mg/m2 i.v., followed by rituximab 375 mg/m2 i.v. every two months for four additional doses.
Measure Participants	219	219
Number [Participants]	36 16.4%	44 20.1%

3. Secondary Outcome

Title	Number of Participants With Overall Response (OR)
Description	The overall response rate (ORR) was defined as the number of participants achieving a CR or partial response (PR). from start of randomization until disease progression, or the start of a new anti-cancer therapy. Disease response was assessed according to modified 2007 Revised Response Criteria for Malignant Lymphoma (RRCML). Computed tomography (CT) scans of the neck, thorax, abdomen and pelvis were performed as part of the efficacy evaluation. Bone marrow examination to confirm a suspected complete response (CR) was performed within 8 weeks following the onset of a CT scan confirmed CR.
Time Frame	200 weeks

Outcome Measure Data

Analysis Population Description

The Intent-to-treat (ITT) analysis set, comprised of all randomized participants, was analyzed.

Arm/Group Title	Ofatumumab	Rituximab
Arm/Group Description	Four weekly doses of single agent ofatumumab 1000 mg by intravenous (i.v.) infusion, followed by ofatumumab 1000 mg i.v. every two months for four additional doses.	Four weekly doses of single agent rituximab 375 mg/m2 i.v., followed by rituximab 375 mg/m2 i.v. every two months for four additional doses.
Measure Participants	219	219
Number [Participants]	110 50.2%	144 65.8%

4. Secondary Outcome

Title	Number of Deaths
Description	The number of deaths were assessed.
Time Frame	200 weeks

Outcome Measure Data

Analysis Population Description

The Intent-to-treat (ITT) analysis set, comprised of all randomized participants, was analyzed.

Arm/Group Title	Ofatumumab	Rituximab
Arm/Group Description	Four weekly doses of single agent ofatumumab 1000 mg by intravenous (i.v.) infusion, followed by ofatumumab 1000 mg i.v. every two months for four additional doses.	Four weekly doses of single agent rituximab 375 mg/m2 i.v., followed by rituximab 375 mg/m2 i.v. every two months for four additional doses.
Measure Participants	219	219
Number [Participants]	28 12.8%	30 13.7%

5. Secondary Outcome

Title	Number of Participants With Infection Related Adverse Events
Description	The number of participants with infection related adverse events was assessed.
Time Frame	200 weeks

Outcome Measure Data

Analysis Population Description

The safety set, comprised of all participants who received one dose of study drug, was analyzed.

Arm/Group Title	Ofatumumab	Rituximab
Arm/Group Description	Four weekly doses of single agent ofatumumab 1000 mg by intravenous (i.v.) infusion, followed by ofatumumab 1000 mg i.v. every two months for four additional doses.	Four weekly doses of single agent rituximab 375 mg/m2 i.v., followed by rituximab 375 mg/m2 i.v. every two months for four additional doses.
Measure Participants	217	218
Number [Participants]	69 31.5%	81 37%

6. Secondary Outcome

Title	Number of Participants With Infusion Related Adverse Events Due to Study Drug
Description	The number of participants with infusion related adverse events due to study drug was assessed.
Time Frame	36 weeks + 60 days

Outcome Measure Data

Analysis Population Description

The safety set, comprised of all participants who received one dose of study drug, was analyzed.

Arm/Group Title	Ofatumumab	Rituximab
Arm/Group Description	Four weekly doses of single agent ofatumumab 1000 mg by intravenous (i.v.) infusion, followed by ofatumumab 1000 mg i.v. every two months for four additional doses.	Four weekly doses of single agent rituximab 375 mg/m2 i.v., followed by rituximab 375 mg/m2 i.v. every two months for four additional doses.
Measure Participants	217	218
Number [Participants]	178 81.3%	112 51.1%

7. Secondary Outcome

Title	Number of Participants With Myelosuppression Adverse Events
Description	The number of participants with myelosuppression adverse events was assessed.
Time Frame	200 weeks

Outcome Measure Data

Analysis Population Description

The safety set, comprised of all participants who received one dose of study drug, was analyzed.

Arm/Group Title	Ofatumumab	Rituximab
Arm/Group Description	Four weekly doses of single agent ofatumumab 1000 mg by intravenous (i.v.) infusion, followed by ofatumumab 1000 mg i.v. every two months for four additional doses.	Four weekly doses of single agent rituximab 375 mg/m2 i.v., followed by rituximab 375 mg/m2 i.v. every two months for four additional doses.
Measure Participants	217	218
Number [Participants]	24 11%	41 18.7%

8. Secondary Outcome

Title	Duration of Response (DOR)
Time Frame	200 weeks

Outcome Measure Data

Analysis Population Description

The analysis of this outcome was not performed due to the early termination of the study. Please see the brief summary of the protocol section for additional details.

Arm/Group Title	Ofatumumab	Rituximab
Arm/Group Description	Four weekly doses of single agent ofatumumab 1000 mg by intravenous (i.v.) infusion, followed by ofatumumab 1000 mg i.v. every two months for four additional doses.	Four weekly doses of single agent rituximab 375 mg/m2 i.v., followed by rituximab 375 mg/m2 i.v. every two months for four additional doses.
Measure Participants	0	0

9. Secondary Outcome

Title	Time to Next Treatment
Time Frame	200 weeks

Outcome Measure Data

Analysis Population Description

The analysis of this outcome was not performed due to the early termination of the study. Please see the brief summary of the protocol section for additional details.

Arm/Group Title	Ofatumumab	Rituximab
Arm/Group Description	Four weekly doses of single agent ofatumumab 1000 mg by intravenous (i.v.) infusion, followed by ofatumumab 1000 mg i.v. every two months for four additional doses.	Four weekly doses of single agent rituximab 375 mg/m2 i.v., followed by rituximab 375 mg/m2 i.v. every two months for four additional doses.
Measure Participants	0	0

10. Secondary Outcome

Title	Pharmacokinetics
Time Frame	70 weeks

Outcome Measure Data

Analysis Population Description

The analysis of this outcome was not performed due to the early termination of the study. Please see the brief summary of the protocol section for additional details.

Arm/Group Title	Ofatumumab	Rituximab
Arm/Group Description	Four weekly doses of single agent ofatumumab 1000 mg by intravenous (i.v.) infusion, followed by ofatumumab 1000 mg i.v. every two months for four additional doses.	Four weekly doses of single agent rituximab 375 mg/m2 i.v., followed by rituximab 375 mg/m2 i.v. every two months for four additional doses.
Measure Participants	0	0

Adverse Events

Arm/Group Title	Ofatumumab		Rituximab
Arm/Group Description	Four weekly doses of single agent ofatumumab 1000 mg by intravenous (i.v.) infusion, followed by ofatumumab 1000 mg i.v. every two months for four additional doses.		Four weekly doses of single agent rituximab 375 mg/m2 i.v., followed by rituximab 375 mg/m2 i.v. every two months for four additional doses.
All Cause Mortality
	Ofatumumab		Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ofatumumab		Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/217 (17.5%)		37/218 (17%)
Blood and lymphatic system disorders
Anaemia	1/217 (0.5%)		0/218 (0%)
Febrile neutropenia	1/217 (0.5%)		0/218 (0%)
Lymphopenia	1/217 (0.5%)		0/218 (0%)
Neutropenia	2/217 (0.9%)		1/218 (0.5%)
Pancytopenia	0/217 (0%)		1/218 (0.5%)
Cardiac disorders
Acute myocardial infarction	0/217 (0%)		1/218 (0.5%)
Atrial fibrillation	1/217 (0.5%)		2/218 (0.9%)
Cardiac failure congestive	0/217 (0%)		1/218 (0.5%)
Ear and labyrinth disorders
Otosclerosis	0/217 (0%)		1/218 (0.5%)
Eye disorders
Cataract	0/217 (0%)		1/218 (0.5%)
Gastrointestinal disorders
Constipation	0/217 (0%)		1/218 (0.5%)
Crohn's disease	1/217 (0.5%)		0/218 (0%)
Diarrhoea	1/217 (0.5%)		0/218 (0%)
Ileus	1/217 (0.5%)		0/218 (0%)
Intestinal obstruction	0/217 (0%)		2/218 (0.9%)
Intestinal perforation	1/217 (0.5%)		0/218 (0%)
Mesenteric vein thrombosis	0/217 (0%)		1/218 (0.5%)
Nausea	0/217 (0%)		1/218 (0.5%)
Rectal haemorrhage	0/217 (0%)		1/218 (0.5%)
Retroperitoneal haematoma	1/217 (0.5%)		0/218 (0%)
Small intestinal obstruction	0/217 (0%)		1/218 (0.5%)
Upper gastrointestinal haemorrhage	1/217 (0.5%)		0/218 (0%)
General disorders
Asthenia	0/217 (0%)		1/218 (0.5%)
Chills	1/217 (0.5%)		0/218 (0%)
Fatigue	0/217 (0%)		1/218 (0.5%)
General physical health deterioration	0/217 (0%)		1/218 (0.5%)
Non-cardiac chest pain	0/217 (0%)		1/218 (0.5%)
Performance status decreased	1/217 (0.5%)		0/218 (0%)
Pyrexia	0/217 (0%)		2/218 (0.9%)
Hepatobiliary disorders
Hepatotoxicity	0/217 (0%)		1/218 (0.5%)
Infections and infestations
Appendicitis	1/217 (0.5%)		0/218 (0%)
Bronchitis	1/217 (0.5%)		0/218 (0%)
Herpes zoster	1/217 (0.5%)		0/218 (0%)
Infection	1/217 (0.5%)		0/218 (0%)
Lymph gland infection	1/217 (0.5%)		0/218 (0%)
Neutropenic sepsis	0/217 (0%)		1/218 (0.5%)
Pneumonia	2/217 (0.9%)		5/218 (2.3%)
Respiratory syncytial virus infection	1/217 (0.5%)		0/218 (0%)
Sepsis	1/217 (0.5%)		3/218 (1.4%)
Septic shock	1/217 (0.5%)		0/218 (0%)
Skin infection	0/217 (0%)		1/218 (0.5%)
Urosepsis	0/217 (0%)		1/218 (0.5%)
Injury, poisoning and procedural complications
Fall	1/217 (0.5%)		0/218 (0%)
Infusion related reaction	5/217 (2.3%)		0/218 (0%)
Pubis fracture	1/217 (0.5%)		0/218 (0%)
Investigations
Alanine aminotransferase increased	1/217 (0.5%)		0/218 (0%)
Aspartate aminotransferase increased	1/217 (0.5%)		0/218 (0%)
Metabolism and nutrition disorders
Dehydration	0/217 (0%)		1/218 (0.5%)
Hyponatraemia	0/217 (0%)		1/218 (0.5%)
Musculoskeletal and connective tissue disorders
Back pain	1/217 (0.5%)		1/218 (0.5%)
Bursitis	1/217 (0.5%)		0/218 (0%)
Musculoskeletal pain	1/217 (0.5%)		0/218 (0%)
Pain in extremity	0/217 (0%)		1/218 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of appendix	1/217 (0.5%)		0/218 (0%)
Adenocarcinoma of colon	1/217 (0.5%)		0/218 (0%)
Carcinoid tumour pulmonary	0/217 (0%)		1/218 (0.5%)
Colorectal cancer	1/217 (0.5%)		0/218 (0%)
Hepatic neoplasm	0/217 (0%)		1/218 (0.5%)
Hepatocellular carcinoma	1/217 (0.5%)		0/218 (0%)
Lung adenocarcinoma	1/217 (0.5%)		0/218 (0%)
Malignant pleural effusion	0/217 (0%)		1/218 (0.5%)
Mycosis fungoides	1/217 (0.5%)		0/218 (0%)
Myelodysplastic syndrome	1/217 (0.5%)		0/218 (0%)
Oesophageal carcinoma	0/217 (0%)		1/218 (0.5%)
Prostate cancer	1/217 (0.5%)		0/218 (0%)
Squamous cell carcinoma	0/217 (0%)		1/218 (0.5%)
Squamous cell carcinoma of skin	2/217 (0.9%)		0/218 (0%)
Transitional cell carcinoma	1/217 (0.5%)		0/218 (0%)
Nervous system disorders
Cerebrovascular accident	0/217 (0%)		1/218 (0.5%)
Normal pressure hydrocephalus	1/217 (0.5%)		0/218 (0%)
Presyncope	1/217 (0.5%)		0/218 (0%)
Syncope	0/217 (0%)		1/218 (0.5%)
Transient ischaemic attack	1/217 (0.5%)		0/218 (0%)
Psychiatric disorders
Depression	0/217 (0%)		1/218 (0.5%)
Renal and urinary disorders
Acute kidney injury	1/217 (0.5%)		1/218 (0.5%)
Hydronephrosis	0/217 (0%)		1/218 (0.5%)
Renal colic	0/217 (0%)		1/218 (0.5%)
Renal failure	0/217 (0%)		1/218 (0.5%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/217 (0%)		1/218 (0.5%)
Asthma	1/217 (0.5%)		0/218 (0%)
Bronchopneumopathy	0/217 (0%)		1/218 (0.5%)
Cough	0/217 (0%)		2/218 (0.9%)
Dyspnoea	0/217 (0%)		2/218 (0.9%)
Lung disorder	0/217 (0%)		1/218 (0.5%)
Pleural effusion	1/217 (0.5%)		1/218 (0.5%)
Pulmonary embolism	0/217 (0%)		2/218 (0.9%)
Skin and subcutaneous tissue disorders
Toxic epidermal necrolysis	1/217 (0.5%)		0/218 (0%)
Vascular disorders
Hypotension	1/217 (0.5%)		0/218 (0%)
Poor peripheral circulation	0/217 (0%)		1/218 (0.5%)
Shock haemorrhagic	1/217 (0.5%)		0/218 (0%)
Other (Not Including Serious) Adverse Events
	Ofatumumab		Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	177/217 (81.6%)		150/218 (68.8%)
Blood and lymphatic system disorders
Neutropenia	6/217 (2.8%)		16/218 (7.3%)
Gastrointestinal disorders
Abdominal pain	12/217 (5.5%)		7/218 (3.2%)
Constipation	17/217 (7.8%)		11/218 (5%)
Diarrhoea	20/217 (9.2%)		15/218 (6.9%)
Nausea	19/217 (8.8%)		16/218 (7.3%)
General disorders
Asthenia	9/217 (4.1%)		14/218 (6.4%)
Chills	8/217 (3.7%)		13/218 (6%)
Fatigue	21/217 (9.7%)		28/218 (12.8%)
Pyrexia	9/217 (4.1%)		21/218 (9.6%)
Infections and infestations
Nasopharyngitis	14/217 (6.5%)		22/218 (10.1%)
Upper respiratory tract infection	13/217 (6%)		11/218 (5%)
Injury, poisoning and procedural complications
Infusion related reaction	40/217 (18.4%)		19/218 (8.7%)
Investigations
Alanine aminotransferase increased	3/217 (1.4%)		11/218 (5%)
Neutrophil count decreased	10/217 (4.6%)		16/218 (7.3%)
White blood cell count decreased	12/217 (5.5%)		23/218 (10.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	8/217 (3.7%)		11/218 (5%)
Nervous system disorders
Headache	11/217 (5.1%)		20/218 (9.2%)
Psychiatric disorders
Insomnia	14/217 (6.5%)		7/218 (3.2%)
Respiratory, thoracic and mediastinal disorders
Cough	9/217 (4.1%)		18/218 (8.3%)
Dyspnoea	13/217 (6%)		13/218 (6%)
Oropharyngeal discomfort	6/217 (2.8%)		11/218 (5%)
Oropharyngeal pain	12/217 (5.5%)		11/218 (5%)
Skin and subcutaneous tissue disorders
Pruritus	20/217 (9.2%)		14/218 (6.4%)
Rash	42/217 (19.4%)		11/218 (5%)
Rash maculo-papular	16/217 (7.4%)		2/218 (0.9%)
Urticaria	41/217 (18.9%)		3/218 (1.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.