Overview

This trial is active, not recruiting.

Condition lymphoma, non-hodgkin
Treatments ofatumumab, bendamustine
Phase phase 2
Sponsor Novartis Pharmaceuticals
Start date May 2011
End date August 2021
Trial size 53 participants
Trial identifier NCT01294579, 114612

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Masking open label
Primary purpose treatment
Arm
(Experimental)
ofatumumab and Bendamustine
ofatumumab
1000 mg intravenous (IV) on day 1 of each cycle (cycles 1-6) for induction phase 1000 mg IV every 2 months for 2 years
bendamustine
90 mg/m2 on day 1 (after the ofatumumab infusion) and day 2 of each cycle (cycles 1-6)

Primary Outcomes

Measure
Complete Remission (CR) Rate of Induction Therapy
time frame: 157 Weeks

Secondary Outcomes

Measure
Overall Response Rate (PR +CR) of Induction therapy
time frame: 157 Weeks
Conversion of PR to CR with Maintenance Ofatumumab
time frame: 260 weeks
Progression Free Survival (PFS)
time frame: 260 weeks
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of Combination of Ofatumumab and Bendamustine
time frame: 165 Weeks
Pharmacokinetic Profile Which Includes Measuring Blood Levels of Ofatumumab and Bendamustine in Combination and Ofatumumab alone During Maintenance Treatment and Measuring Blood Levels of Circulating B cell
time frame: 261 Weeks

Eligibility Criteria

Male or female participants at least 18 years old.

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.

Additional Information

Official title A Phase II Open-Label Study of Ofatumumab and Bendamustine Followed by Maintenance Ofatumumab for Indolent B-cell Non-Hodgkin's Lymphoma (B-NHL) Which Has Relapsed After Rituximab or a Rituximab Containing Therapy
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Novartis.