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

Non-Hodgkin's Lymphoma Clinical Trial

— HOMER  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01200589
• Other study ID #: 113676
• Status: Terminated
• Phase: Phase 3
• Start date: October 11, 2010
• Est. completion date: December 19, 2016

Study information

• Verified date: April 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 438
• Est. completion date: December 19, 2016
• Est. primary completion date: December 19, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

1. Follicular lymphoma Grades 1, 2, 3 A

2. Small lymphocytic lymphoma (SLL)

3. Marginal zone lymphoma

4. Lymphoplasmacytic lymphoma

2. 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.

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

4. 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.

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

6. Age =18 years.

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

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

9. 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.

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

1. Cytopenias

2. 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

3. Progressive or massive lymphadenopathy OR

4. 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:

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

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

3. ALT or AST > 3 x ULN

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

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

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

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

1. Lactating women.

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

3. 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).

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

15. 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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma

Intervention

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.
• Rituximab
sourced locally from commercial stock
• Ofatumumab
Four weekly doses of single agent ofatumumab (1000 mg), followed by ofatumumab (1000 mg) every two months for four additional doses.
• Rituximab
Four weekly doses of single agent rituximab (375 mg/m2), followed by rituximab (375 mg/m2) every two months for four additional doses.

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Antwerpen
Belgium	Novartis Investigative Site	Antwerpen
Belgium	Novartis Investigative Site	Brugge
Belgium	Novartis Investigative Site	Brussels
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Kortrijk
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Wilrijk
Brazil	Novartis Investigative Site	Barretos	São Paulo
Brazil	Novartis Investigative Site	Betim	Minas Gerais
Brazil	Novartis Investigative Site	Curitiba	Paraná
Brazil	Novartis Investigative Site	Jau	São Paulo
Brazil	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul
Brazil	Novartis Investigative Site	Rio de Janeiro
Brazil	Novartis Investigative Site	Rio de Janeiro
Brazil	Novartis Investigative Site	Salvador	Bahía
Brazil	Novartis Investigative Site	Sao Paulo	São Paulo
Brazil	Novartis Investigative Site	Sao Paulo	São Paulo
Brazil	Novartis Investigative Site	Sao Paulo	São Paulo
Brazil	Novartis Investigative Site	Sao Paulo	São Paulo
Bulgaria	Novartis Investigative Site	Pleven
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Varna
Canada	Novartis Investigative Site	Kitchener	Ontario
Canada	Novartis Investigative Site	Moncton	New Brunswick
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Sherbrooke	Quebec
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Tianjin
Czechia	Novartis Investigative Site	Brno
Czechia	Novartis Investigative Site	Hradec Kralove
Czechia	Novartis Investigative Site	Ostrava
Czechia	Novartis Investigative Site	Praha 2
France	Novartis Investigative Site	Boulogne sur Mer Cedex
France	Novartis Investigative Site	Clermont-Ferrand Cedex 1
France	Novartis Investigative Site	La Roche sur Yon Cedex 9
France	Novartis Investigative Site	Le Mans
France	Novartis Investigative Site	Montpellier cedex 5
France	Novartis Investigative Site	Pessac cedex
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Gyor
Hungary	Novartis Investigative Site	Szeged
Japan	Novartis Investigative Site	Aichi
Japan	Novartis Investigative Site	Kyoto
Japan	Novartis Investigative Site	Miyagi
Japan	Novartis Investigative Site	Nagasaki
Japan	Novartis Investigative Site	Saitama
Japan	Novartis Investigative Site	Tochigi
Japan	Novartis Investigative Site	Tokyo
Japan	Novartis Investigative Site	Tokyo
Korea, Republic of	Novartis Investigative Site	Busan
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Peru	Novartis Investigative Site	Lima
Peru	Novartis Investigative Site	Lima
Peru	Novartis Investigative Site	Lima
Peru	Novartis Investigative Site	Miraflores	Lima
Peru	Novartis Investigative Site	San Isidro	Lima
Puerto Rico	Novartis Investigative Site	San Juan
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigative Site	Martin
South Africa	Novartis Investigative Site	Athlone Park, Amanzimtoti
South Africa	Novartis Investigative Site	Parktown	Gauteng
South Africa	Novartis Investigative Site	Port Elizabeth
South Africa	Novartis Investigative Site	Saxonwold, Johannesburg
Ukraine	Novartis Investigative Site	Donetsk
Ukraine	Novartis Investigative Site	Kyiv
Ukraine	Novartis Investigative Site	Kyiv
Ukraine	Novartis Investigative Site	Lviv
Ukraine	Novartis Investigative Site	Makiivka
Ukraine	Novartis Investigative Site	Simferopil
United States	Novartis Investigative Site	Albuquerque	New Mexico
United States	Novartis Investigative Site	Albuquerque	New Mexico
United States	Novartis Investigative Site	Ames	Iowa
United States	Novartis Investigative Site	Anchorage	Alaska
United States	Novartis Investigative Site	Anderson	Indiana
United States	Novartis Investigative Site	Bismarck	North Dakota
United States	Novartis Investigative Site	Bozeman	Montana
United States	Novartis Investigative Site	Canton	Ohio
United States	Novartis Investigative Site	Canton	Ohio
United States	Novartis Investigative Site	Chattanooga	Tennessee
United States	Novartis Investigative Site	Columbia	Missouri
United States	Novartis Investigative Site	Danville	Pennsylvania
United States	Novartis Investigative Site	Ephrata	Pennsylvania
United States	Novartis Investigative Site	Evanston	Illinois
United States	Novartis Investigative Site	Fort Sam Houston	Texas
United States	Novartis Investigative Site	Fredericksburg	Virginia
United States	Novartis Investigative Site	Germantown	Tennessee
United States	Novartis Investigative Site	Gilbert	Arizona
United States	Novartis Investigative Site	Grand Rapids	Michigan
United States	Novartis Investigative Site	Greenbrae	California
United States	Novartis Investigative Site	Greensboro	North Carolina
United States	Novartis Investigative Site	Hot Springs	Arkansas
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Jackson	Mississippi
United States	Novartis Investigative Site	Kalamazoo	Michigan
United States	Novartis Investigative Site	Kansas City	Missouri
United States	Novartis Investigative Site	Kennewick	Washington
United States	Novartis Investigative Site	Kirkland	Washington
United States	Novartis Investigative Site	Knoxville	Tennessee
United States	Novartis Investigative Site	Lake Success	New York
United States	Novartis Investigative Site	Lakeland	Florida
United States	Novartis Investigative Site	Lancaster	Pennsylvania
United States	Novartis Investigative Site	Lincoln	Nebraska
United States	Novartis Investigative Site	Lincoln	Nebraska
United States	Novartis Investigative Site	Macon	Georgia
United States	Novartis Investigative Site	Marietta	Georgia
United States	Novartis Investigative Site	Metairie	Louisiana
United States	Novartis Investigative Site	Monterey	California
United States	Novartis Investigative Site	Mount Kisco	New York
United States	Novartis Investigative Site	Mount Sterling	Kentucky
United States	Novartis Investigative Site	Mount Vernon	Washington
United States	Novartis Investigative Site	New Milford	Connecticut
United States	Novartis Investigative Site	Ogden	Utah
United States	Novartis Investigative Site	Orlando	Florida
United States	Novartis Investigative Site	Pembroke Pines	Florida
United States	Novartis Investigative Site	Peoria	Illinois
United States	Novartis Investigative Site	Pleasant Hill	California
United States	Novartis Investigative Site	Port Saint Lucie	Florida
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Quincy	Illinois
United States	Novartis Investigative Site	Rancho Mirage	California
United States	Novartis Investigative Site	Saint Joseph	Missouri
United States	Novartis Investigative Site	Salinas	California
United States	Novartis Investigative Site	Salt Lake City	Utah
United States	Novartis Investigative Site	San Diego	California
United States	Novartis Investigative Site	San Pablo	California
United States	Novartis Investigative Site	Santa Monica	California
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Sequim	Washington
United States	Novartis Investigative Site	Shreveport	Louisiana
United States	Novartis Investigative Site	Silver Spring	Maryland
United States	Novartis Investigative Site	Skokie	Illinois
United States	Novartis Investigative Site	Spokane	Washington
United States	Novartis Investigative Site	Springfield	Missouri
United States	Novartis Investigative Site	Torrington	Connecticut
United States	Novartis Investigative Site	Waterville	Maine
United States	Novartis Investigative Site	West Palm Beach	Florida
United States	Novartis Investigative Site	Willow Grove	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals	GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Czechia,  France,  Hungary,  Japan,  Korea, Republic of,  Peru,  Puerto Rico,  Slovakia,  South Africa,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of Participants With Complete Response (CR)	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.	200 weeks
Secondary	Number of Participants With Overall Response (OR)	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.	200 weeks
Secondary	Number of Deaths	The number of deaths were assessed.	200 weeks
Secondary	Number of Participants With Infection Related Adverse Events	The number of participants with infection related adverse events was assessed.	200 weeks
Secondary	Number of Participants With Infusion Related Adverse Events Due to Study Drug	The number of participants with infusion related adverse events due to study drug was assessed.	36 weeks + 60 days
Secondary	Number of Participants With Myelosuppression Adverse Events	The number of participants with myelosuppression adverse events was assessed.	200 weeks
Secondary	Duration of Response (DOR)		200 weeks
Secondary	Time to Next Treatment		200 weeks
Secondary	Pharmacokinetics		70 weeks