Ofatumumab and Bendamustine Followed by Maintenance Ofatumumab for Rituximab Relapsed Indolent B-cell Non-Hodgkin's Lymphoma (B-NHL)
Conditions
Lymphoma, Non-Hodgkin
Conditions: official terms
Lymphoma - Lymphoma, B-Cell - Lymphoma, Non-Hodgkin
Conditions: Keywords
Non-Hodgkin's Lymphoma, Ofatumumab, Rituximab, Relapsed, Bendamustine
Study Type
Interventional
Study Phase
Phase 2
Study Design
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Ofatumumab Type: Biological
Name: Bendamustine Type: Drug
Overall Status
Recruiting
Summary
The purpose of this phase II open label study is to evaluate the safety and efficacy of ofatumumab and bendamustine followed by maintenance ofatumumab in subjects with indolent B-NHL who have relapsed after Rituximab treatment. A maximum of 53 subjects at least 18 years old with Small lymphocytic, lymphoplasmacytic, marginal zone lymphoma, or follicular lymphoma; Grades 1, 2 and 3a, will be enrolled (34 in Stage 1 and 19 in Stage 2). Subjects should have Rituximab-sensitive disease, defined as a Partial Remission (PR) or Complete Remission (CR) to the last rituximab-containing therapy lasting at least 6 months following completion of therapy or subjects should have relapse or disease progression following response to prior rituximab-based therapy and with a Eastern Cooperative Oncology Group (ECOG) Performance status of 0 1 or 2. During the induction phase, ofatumumab 1000 mg IV on day 1 of each cycle (cycles 1-6) will be followed by Bendamustine 90 mg/m2 IV on days 1, 2 of each cycle (cycles 1-6).During the maintenance phase, subjects with a PR or CR after the induction phase will receive ofatumumab 1000 mg IV every 2 months for 2 years.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Signed written informed consent

- Small lymphocytic, lymphoplasmacytic, marginal zone lymphoma, and follicular lymphoma; Grades 1, 2 and 3a, defined according to World Health organization (WHO) guidelines. [Tefferi, 2008]

- Tumor verified to be CD20+ (based on local evaluation), from a current or previous tissue biopsy. Tissue biopsy should be repeated if no report or specimen is available, CD20 staining was not previously performed, or there is clinical suspicion that the indolent lymphoma has transformed to aggressive lymphoma/higher malignancy grade.

- Rituximab-sensitive disease, defined as a Partial Remission (PR) or Complete Remission (CR) to the last rituximab-containing therapy lasting at least 6 months following completion of therapy. Last rituximab-containing therapy is defined as the last therapy regimen containing at least one full dose of rituximab.

- Relapse or disease progression following response to prior rituximab-based therapy, requiring treatment by 2007 Revised Response Criteria for Malignant Lymphoma (RRCML) guidelines.

- CT imaging in screening (based on local evaluation) showing 2 or more clearly demarcated lesions with a largest diameter > 1.5 cm, or 1 clearly demarcated lesion with a largest diameter > 2.0 cm.

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

- Age ≥ 18 years.

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

- Women of childbearing potential must have a negative serum pregnancy test within 14 days of first dose of study treatment and agree to use effective contraception during the study and for one year following the last dose of study drug.

- Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from 2 weeks prior to administration of the first dose of study treatment until one year after the last dose of study treatment.

- Must not be on any prohibited medications.

- Subjects who have received prior bendamustine are eligible if they achieved a response (CR/PR) which lasted > 6 months after the end of bendamustine containing treatment.

Exclusion Criteria:

- Lactating women

- CLL, Grade 3b follicular lymphoma or evidence that the indolent lymphoma has transformed to aggressive lymphoma. Subjects suspicious for transformation should undergo a biopsy to exclude the possibility of transformation. Subjects with a previous diagnosis of small lymphocytic leukemia (SLL) and a screening monoclonal B-lymphocyte count of ≥ 5000/µl are defined by 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria to have CLL; such patients are NOT eligible for this study.

- Rituximab-refractory disease, defined as failure to respond to or progression within 6 months of completing rituximab or rituximab-containing combination therapy.

- Previous treatment with ofatumumab.

- Previous radioimmunotherapy (RIT) within 6 months of study entry. Subjects who have received RIT must have attained a PR or CR lasting at least 6 months, and must have recovered from any hematologic or other toxicity.

- Previous allogeneic stem cell transplantation at any time OR autologous stem cell transplantation within 6 months of study entry.

- Prior use of monoclonal antibody (other than anti CD20) within 3 months prior to randomization. Chemotherapy or other systemic lymphoma therapy within 4 weeks of study entry.

- Received treatment with an investigational agent within 4 weeks of study entry, or is actively participating in another interventional clinical study.

- Known Central Nervous System (CNS) involvement by lymphoma.

- Current or previous other malignancy within 2 years of study entry. Exception: Subjects who have been disease-free for 2 years or more, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.

- Chronic or currently active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment including, but not limited to: chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, active Hepatitis C, and known HIV disease. All Human Immunodeficient virus (HIV)-positive subjects are excluded from this study, regardless of whether they have an Acquired Immunodeficiency Syndrome (AIDS) defining disease and/or are on antiviral therapy.

- Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months of study entry, uncontrolled congestive heart failure, and uncontrolled arrhythmia. Subjects with congestive heart disease or arrhythmia 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.

- Positive serology for Hepatitis B (HB) defined as a positive test for Hepatitis B surface antigen (HBsAg). In addition, if negative for HBsAg but (Hepatitis B core antibody (HBcAb) positive (regardless of Hepatitis B surface antibody [HBsAb] status), a HB DNA test will be performed and if positive the subject will be excluded. If HBV DNA is negative, subject may be included but must undergo HBV DNA monitoring. Prophylactic antiviral therapy may be initiated at the discretion of the investigator.

- Current active liver or biliary disease. Exception: Subjects with Gilbert's syndrome or asymptomatic gallstones, liver metastases related to indolent NHL or otherwise stable chronic liver disease per investigator assessment, are eligible.

- Screening laboratory values:

Neutrophils < 1.5 x 109/L (unless due to NHL involvement of the bone marrow). Platelets < 100 x 109/L (unless due to NHL involvement of the bone marrow). Serum creatinine ≥2.0 mg/dL; subjects with serum creatinine ≥2.0 mg/dL are eligible if the creatinine clearance (Cockcroft Gault equation [Cockcroft, 1976]) is ≥40 mL/min.

Total bilirubin > 1.5 times ULN [upper normal limit] (unless due to liver involvement by NHL or Gilbert's disease).

Transaminases > 3 times ULN (unless due to NHL involvement).

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

- Known or suspected hypersensitivity to ofatumumab, bendamustine or mannitol.
Locations
GSK Investigational Site
Chandler, Arizona, United States
Status: Recruiting
Contact: US GSK Clinical Trials Call Center - 877-379-3718 - GSKClinicalSupportHD@gsk.com
GSK Investigational Site
Burbank, California, United States
Status: Completed
GSK Investigational Site
Fresno, California, United States
Status: Completed
GSK Investigational Site
Oxnard, California, United States
Status: Completed
GSK Investigational Site
Aurora, Colorado, United States
Status: Recruiting
Contact: US GSK Clinical Trials Call Center - 877-379-3718 - GSKClinicalSupportHD@gsk.com
GSK Investigational Site
Orange Park, Florida, United States
Status: Recruiting
Contact: US GSK Clinical Trials Call Center - 877-379-3718 - GSKClinicalSupportHD@gsk.com
GSK Investigational Site
Burlington, Massachusetts, United States
Status: Terminated
GSK Investigational Site
Omaha, Nebraska, United States
Status: Completed
GSK Investigational Site
Las Vegas, Nevada, United States
Status: Recruiting
Contact: US GSK Clinical Trials Call Center - 877-379-3718 - GSKClinicalSupportHD@gsk.com
GSK Investigational Site
Cary, North Carolina, United States
Status: Recruiting
Contact: US GSK Clinical Trials Call Center - 877-379-3718 - GSKClinicalSupportHD@gsk.com
GSK Investigational Site
Charlotte, North Carolina, United States
Status: Completed
GSK Investigational Site
Raleigh, North Carolina, United States
Status: Terminated
GSK Investigational Site
Kettering, Ohio, United States
Status: Completed
GSK Investigational Site
Eugene, Oregon, United States
Status: Recruiting
Contact: US GSK Clinical Trials Call Center - 877-379-3718 - GSKClinicalSupportHD@gsk.com
GSK Investigational Site
Charleston, South Carolina, United States
Status: Terminated
GSK Investigational Site
Greenville, South Carolina, United States
Status: Recruiting
Contact: US GSK Clinical Trials Call Center - 877-379-3718 - GSKClinicalSupportHD@gsk.com
GSK Investigational Site
San Antonio, Texas, United States
Status: Recruiting
Contact: US GSK Clinical Trials Call Center - 877-379-3718 - GSKClinicalSupportHD@gsk.com
GSK Investigational Site
Sherman, Texas, United States
Status: Not yet recruiting
Contact: US GSK Clinical Trials Call Center - 877-379-3718 - GSKClinicalSupportHD@gsk.com
GSK Investigational Site
Tyler, Texas, United States
Status: Recruiting
Contact: US GSK Clinical Trials Call Center - 877-379-3718 - GSKClinicalSupportHD@gsk.com
GSK Investigational Site
Waco, Texas, United States
Status: Recruiting
Contact: US GSK Clinical Trials Call Center - 877-379-3718 - GSKClinicalSupportHD@gsk.com
GSK Investigational Site
Vancouver, Washington, United States
Status: Recruiting
Contact: US GSK Clinical Trials Call Center - 877-379-3718 - GSKClinicalSupportHD@gsk.com
GSK Investigational Site
Yakima, Washington, United States
Status: Recruiting
Contact: US GSK Clinical Trials Call Center - 877-379-3718 - GSKClinicalSupportHD@gsk.com
Start Date
May 2011
Completion Date
July 2020
Sponsors
GlaxoSmithKline
Source
GlaxoSmithKline
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page