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

NCT01200589 | Terminated Phase 3 Results DMC

• 1 other identifier: 113676
• Study Type: interventional
• Target: 438
• Locations: 16 countries
• Sites: 155

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.

Conditions

Non-Hodgkin's Lymphoma

Keywords

Randomized trial; Ofatumumab; Rituximab; Indolent B-Cell Non Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) - Number of Participants With PFS Events

  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.

  200 weeks

Secondary Outcomes (9)

• Number of Participants With Complete Response (CR)

  200 weeks

• Number of Participants With Overall Response (OR)

  200 weeks

• Number of Deaths

  200 weeks

• Number of Participants With Infection Related Adverse Events

  200 weeks

• Number of Participants With Infusion Related Adverse Events Due to Study Drug

  36 weeks + 60 days

Study Arms (2)

Arm A: Ofatumumab

EXPERIMENTAL

Four weekly doses of single agent ofatumumab (1000 mg), followed by ofatumumab (1000 mg) every two months for four additional doses.

Biological: Ofatumumab

Arm B: Rituximab

ACTIVE COMPARATOR

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

Interventions

Ofatumumab BIOLOGICAL

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.

Also known as: Arzerra

Arm A: Ofatumumab

Rituximab BIOLOGICAL

sourced locally from commercial stock

Also known as: Mabthera, Rituxan

Arm B: Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Indolent NHL subtypes defined according to World Health Organization guidelines:
• Follicular lymphoma Grades 1, 2, 3 A
• Small lymphocytic lymphoma (SLL)
• Marginal zone lymphoma
• Lymphoplasmacytic lymphoma
• 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.
• Relapse or disease progression following response to prior rituximab-based therapy, as defined by 2007 RRCML criteria, which requires therapy.
• 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.
• ECOG Performance Status of 0, 1, or 2.
• Age ≥18 years.
• Life expectancy of at least 6 months in the opinion of the investigator.
• The patient or their legally acceptable representative must be capable of giving written informed consent prior to performing any study-specific tests or procedures.
• 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.
• One or more of the following indications for treatment:
• Cytopenias

You may not qualify if:

• Previous treatment with ofatumumab.
• 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.
• Previous autologous stem cell transplantation within 6 months prior to randomization.
• Previous allogeneic stem cell transplantation.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Screening laboratory values:
• Neutrophils \< 1.5 x 10\^9/L (unless due to iNHL involvement of the bone marrow)
• Platelets \< 50 x 10\^9/L (unless due to iNHL involvement of the bone marrow)
• ALT or AST \> 3 x ULN
• Alkaline phosphatase \> 1.5 x ULN (unless due to lymphoma or a non-malignant, non-hepatic cause such as Paget's disease)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• GlaxoSmithKline: collaborator

Study Sites (155)

Novartis Investigative Site

Anchorage, Alaska, 99508, United States

Location

Novartis Investigative Site

Gilbert, Arizona, 85234, United States

Location

Novartis Investigative Site

Hot Springs, Arkansas, 71913, United States

Location

Novartis Investigative Site

Greenbrae, California, 94904, United States

Location

Novartis Investigative Site

Monterey, California, 93940, United States

Location

Novartis Investigative Site

Pleasant Hill, California, 94523, United States

Location

Novartis Investigative Site

Rancho Mirage, California, 92270, United States

Location

Novartis Investigative Site

Salinas, California, 93901, United States

Location

Novartis Investigative Site

San Diego, California, 92123, United States

Location

Novartis Investigative Site

San Pablo, California, 94806, United States

Location

Novartis Investigative Site

Santa Monica, California, 90403, United States

Location

Novartis Investigative Site

New Milford, Connecticut, 06776, United States

Location

Novartis Investigative Site

Torrington, Connecticut, 06790, United States

Location

Novartis Investigative Site

Lakeland, Florida, 33805, United States

Location

Novartis Investigative Site

Orlando, Florida, 32806, United States

Location

Novartis Investigative Site

Pembroke Pines, Florida, 33028, United States

Location

Novartis Investigative Site

Port Saint Lucie, Florida, 34952, United States

Location

Novartis Investigative Site

West Palm Beach, Florida, 33401, United States

Location

Novartis Investigative Site

Macon, Georgia, 31201-8300, United States

Location

Novartis Investigative Site

Marietta, Georgia, 30060, United States

Location

Novartis Investigative Site

Evanston, Illinois, 60201, United States

Location

Novartis Investigative Site

Peoria, Illinois, 61615, United States

Location

Novartis Investigative Site

Quincy, Illinois, 62301, United States

Location

Novartis Investigative Site

Skokie, Illinois, 60076, United States

Location

Novartis Investigative Site

Anderson, Indiana, 46016, United States

Location

Novartis Investigative Site

Indianapolis, Indiana, 46237, United States

Location

Novartis Investigative Site

Ames, Iowa, 50010, United States

Location

Novartis Investigative Site

Mount Sterling, Kentucky, 40353, United States

Location

Novartis Investigative Site

Metairie, Louisiana, 70006, United States

Location

Novartis Investigative Site

Shreveport, Louisiana, 71103, United States

Location

Novartis Investigative Site

Waterville, Maine, 04901, United States

Location

Novartis Investigative Site

Silver Spring, Maryland, 20910, United States

Location

Novartis Investigative Site

Grand Rapids, Michigan, 49503, United States

Location

Novartis Investigative Site

Kalamazoo, Michigan, 49007, United States

Location

Novartis Investigative Site

Jackson, Mississippi, 39202, United States

Location

Novartis Investigative Site

Columbia, Missouri, 65201, United States

Location

Novartis Investigative Site

Kansas City, Missouri, 64111, United States

Location

Novartis Investigative Site

Saint Joseph, Missouri, 64507, United States

Location

Novartis Investigative Site

Springfield, Missouri, 65807, United States

Location

Novartis Investigative Site

Bozeman, Montana, 59715, United States

Location

Novartis Investigative Site

Lincoln, Nebraska, 68506, United States

Location

Novartis Investigative Site

Lincoln, Nebraska, 68510, United States

Location

Novartis Investigative Site

Albuquerque, New Mexico, 87110, United States

Location

Novartis Investigative Site

Albuquerque, New Mexico, 87131, United States

Location

Novartis Investigative Site

Lake Success, New York, 10042, United States

Location

Novartis Investigative Site

Mount Kisco, New York, 10549, United States

Location

Novartis Investigative Site

Greensboro, North Carolina, 27403, United States

Location

Novartis Investigative Site

Bismarck, North Dakota, 58501, United States

Location

Novartis Investigative Site

Canton, Ohio, 44708, United States

Location

Novartis Investigative Site

Canton, Ohio, 44710, United States

Location

Novartis Investigative Site

Portland, Oregon, 97213, United States

Location

Novartis Investigative Site

Danville, Pennsylvania, 17822, United States

Location

Novartis Investigative Site

Ephrata, Pennsylvania, 17522, United States

Location

Novartis Investigative Site

Lancaster, Pennsylvania, 17605, United States

Location

Novartis Investigative Site

Willow Grove, Pennsylvania, 19090, United States

Location

Novartis Investigative Site

Chattanooga, Tennessee, 37404, United States

Location

Novartis Investigative Site

Germantown, Tennessee, 38138, United States

Location

Novartis Investigative Site

Knoxville, Tennessee, 37916, United States

Location

Novartis Investigative Site

Fort Sam Houston, Texas, 78234, United States

Location

Novartis Investigative Site

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Ogden, Utah, 84403, United States

Location

Novartis Investigative Site

Salt Lake City, Utah, 84106, United States

Location

Novartis Investigative Site

Fredericksburg, Virginia, 22408, United States

Location

Novartis Investigative Site

Kennewick, Washington, 99336, United States

Location

Novartis Investigative Site

Kirkland, Washington, 98034, United States

Location

Novartis Investigative Site

Mount Vernon, Washington, 98273, United States

Location

Novartis Investigative Site

Seattle, Washington, 98109, United States

Location

Novartis Investigative Site

Seattle, Washington, 98112, United States

Location

Novartis Investigative Site

Sequim, Washington, 98382, United States

Location

Novartis Investigative Site

Spokane, Washington, 99208, United States

Location

Novartis Investigative Site

Antwerp, 2020, Belgium

Location

Novartis Investigative Site

Antwerp, 2060, Belgium

Location

Novartis Investigative Site

Bruges, 8000, Belgium

Location

Novartis Investigative Site

Brussels, 1000, Belgium

Location

Novartis Investigative Site

Brussels, 1090, Belgium

Location

Novartis Investigative Site

Kortrijk, 8500, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Wilrijk, 2610, Belgium

Location

Novartis Investigative Site

Salvador, Estado de Bahia, 41253-190, Brazil

Location

Novartis Investigative Site

Betim, Minas Gerais, 32.651-760, Brazil

Location

Novartis Investigative Site

Curitiba, Paraná, 80060-900, Brazil

Location

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90470-340, Brazil

Location

Novartis Investigative Site

Barretos, São Paulo, 14784-400, Brazil

Location

Novartis Investigative Site

Jaú, São Paulo, 17210-080, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01223-001, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01308-000, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 04039-901, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 05403-000, Brazil

Location

Novartis Investigative Site

Rio de Janeiro, 20230 -130, Brazil

Location

Novartis Investigative Site

Rio de Janeiro, 22793-080, Brazil

Location

Novartis Investigative Site

Pleven, 5800, Bulgaria

Location

Novartis Investigative Site

Plovdiv, 4000, Bulgaria

Location

Novartis Investigative Site

Sofia, 1233, Bulgaria

Location

Novartis Investigative Site

Sofia, 1431, Bulgaria

Location

Novartis Investigative Site

Sofia, Bulgaria

Location

Novartis Investigative Site

Varna, 9010, Bulgaria

Location

Novartis Investigative Site

Moncton, New Brunswick, E1C 6Z8, Canada

Location

Novartis Investigative Site

Kitchener, Ontario, N2G 1G3, Canada

Location

Novartis Investigative Site

Québec, Quebec, G1J 1Z4, Canada

Location

Novartis Investigative Site

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510060, China

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510080, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310003, China

Location

Novartis Investigative Site

Beijing, 100021, China

Location

Novartis Investigative Site

Beijing, 100044, China

Location

Novartis Investigative Site

Beijing, 100071, China

Location

Novartis Investigative Site

Beijing, 100142, China

Location

Novartis Investigative Site

Beijing, 100730, China

Location

Novartis Investigative Site

Shanghai, 200025, China

Location

Novartis Investigative Site

Shanghai, 200032, China

Location

Novartis Investigative Site

Tianjin, 300020, China

Location

Novartis Investigative Site

Brno, 625 00, Czechia

Location

Novartis Investigative Site

Hradec Králové, Czechia

Location

Novartis Investigative Site

Ostrava, 708 52, Czechia

Location

Novartis Investigative Site

Prague, 128 08, Czechia

Location

Novartis Investigative Site

Boulogne-sur-Mer, 62321, France

Location

Novartis Investigative Site

Clermont-Ferrand, 63003, France

Location

Novartis Investigative Site

La Roche-sur-Yon, 85925, France

Location

Novartis Investigative Site

Le Mans, 72015, France

Location

Novartis Investigative Site

Montpellier, 34295, France

Location

Novartis Investigative Site

Pessac, 33604, France

Location

Novartis Investigative Site

Budapest, 1122, Hungary

Location

Novartis Investigative Site

Debrecen, 4012, Hungary

Location

Novartis Investigative Site

Győr, 9023, Hungary

Location

Novartis Investigative Site

Szeged, 6720, Hungary

Location

Novartis Investigative Site

Aichi, 466-8650, Japan

Location

Novartis Investigative Site

Kyoto, 602-8566, Japan

Location

Novartis Investigative Site

Miyagi, 980-8574, Japan

Location

Novartis Investigative Site

Nagasaki, 852-8501, Japan

Location

Novartis Investigative Site

Saitama, 350-8550, Japan

Location

Novartis Investigative Site

Tochigi, 329-0498, Japan

Location

Novartis Investigative Site

Tokyo, 104-0045, Japan

Location

Novartis Investigative Site

Tokyo, 135-8550, Japan

Location

Novartis Investigative Site

Miraflores, Lima region, Lima 18, Peru

Location

Novartis Investigative Site

San Isidro, Lima region, Lima 27, Peru

Location

Novartis Investigative Site

Lima, Lima 11, Peru

Location

Novartis Investigative Site

Lima, Lima 34, Peru

Location

Novartis Investigative Site

Lima, Lima 41, Peru

Location

Novartis Investigative Site

San Juan, 00918, Puerto Rico

Location

Novartis Investigative Site

Bratislava, 833 10, Slovakia

Location

Novartis Investigative Site

Košice, 041 66, Slovakia

Location

Novartis Investigative Site

Martin, 036 59, Slovakia

Location

Novartis Investigative Site

Parktown, Gauteng, 2193, South Africa

Location

Novartis Investigative Site

Athlone Park, Amanzimtoti, 4126, South Africa

Location

Novartis Investigative Site

Port Elizabeth, 6045, South Africa

Location

Novartis Investigative Site

Saxonwold, Johannesburg, 2196, South Africa

Location

Novartis Investigative Site

Busan, 602-715, South Korea

Location

Novartis Investigative Site

Seoul, 120-752, South Korea

Location

Novartis Investigative Site

Seoul, 135-710, South Korea

Location

Novartis Investigative Site

Donetsk, 83045, Ukraine

Location

Novartis Investigative Site

Kyiv, 03022, Ukraine

Location

Novartis Investigative Site

Kyiv, 03115, Ukraine

Location

Novartis Investigative Site

Lviv, 79044, Ukraine

Location

Novartis Investigative Site

Makiivka, 86132, Ukraine

Location

Novartis Investigative Site

Simferopil, 95023, Ukraine

Location

Related Publications (1)

• Maloney DG, Ogura M, Fukuhara N, Davis J, Lasher J, Izquierdo M, Banerjee H, Tobinai K. A phase 3 randomized study (HOMER) of ofatumumab vs rituximab in iNHL relapsed after rituximab-containing therapy. Blood Adv. 2020 Aug 25;4(16):3886-3893. doi: 10.1182/bloodadvances.2020001942.

  PMID: 32810220 DERIVED

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

ofatumumab; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2010
• First Posted: September 13, 2010
• Study Start: October 11, 2010
• Primary Completion: December 19, 2016
• Study Completion: December 19, 2016
• Last Updated: May 16, 2018
• Results First Posted: May 16, 2018

Record last verified: 2018-04

Locations

CZ (4); JP (8); PE (5); UA (6); ZA (4); CN (11); SL (3); PR (1); US (70); BR (12); FR (6); CA (4); BE (8); KR (3); HU (4); BU (6)