Ofatumumab and Bendamustine Followed by Maintenance Ofatumumab for Rituximab Relapsed Indolent B-cell Non-Hodgkin's Lymphoma (B-NHL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT01294579
First received: February 3, 2011
Last updated: March 8, 2016
Last verified: March 2016
  Purpose
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.

Condition Intervention Phase
Lymphoma, Non-Hodgkin
Biological: Ofatumumab
Drug: Bendamustine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Complete Remission (CR) Rate of Induction Therapy [ Time Frame: 157 Weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall Response Rate (PR +CR) of Induction therapy [ Time Frame: 157 Weeks ] [ Designated as safety issue: No ]
  • Conversion of PR to CR with Maintenance Ofatumumab [ Time Frame: 260 weeks ] [ Designated as safety issue: No ]
  • Progression Free Survival (PFS) [ Time Frame: 260 weeks ] [ Designated as safety issue: No ]
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability of Combination of Ofatumumab and Bendamustine [ Time Frame: 165 Weeks ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 53
Study Start Date: May 2011
Estimated Study Completion Date: August 2021
Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open Label Single Arm
ofatumumab and Bendamustine
Biological: 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

Drug: Bendamustine
90 mg/m2 on day 1 (after the ofatumumab infusion) and day 2 of each cycle (cycles 1-6)

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01294579

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals +41613241111

Locations
United States, Arizona
Novartis Investigative Site Recruiting
Chandler, Arizona, United States, 85224
United States, California
Novartis Investigative Site Completed
Burbank, California, United States, 91505
Novartis Investigative Site Completed
Fresno, California, United States, 93720
Novartis Investigative Site Completed
Oxnard, California, United States, 93030
United States, Colorado
Novartis Investigative Site Recruiting
Aurora, Colorado, United States, 80045
United States, Florida
Novartis Investigative Site Recruiting
Orange Park, Florida, United States, 32073
United States, Massachusetts
Novartis Investigative Site Terminated
Burlington, Massachusetts, United States, 01805
United States, Nebraska
Novartis Investigative Site Completed
Omaha, Nebraska, United States, 68198-9200
United States, Nevada
Novartis Investigative Site Recruiting
Las Vegas, Nevada, United States, 89169
United States, North Carolina
Novartis Investigative Site Recruiting
Cary, North Carolina, United States, 27518
Novartis Investigative Site Completed
Charlotte, North Carolina, United States, 28204
Novartis Investigative Site Terminated
Raleigh, North Carolina, United States, 27607
United States, Ohio
Novartis Investigative Site Completed
Kettering, Ohio, United States, 45429
United States, Oregon
Novartis Investigative Site Recruiting
Eugene, Oregon, United States, 97401
United States, South Carolina
Novartis Investigative Site Terminated
Charleston, South Carolina, United States, 29414
Novartis Investigative Site Recruiting
Greenville, South Carolina, United States, 29601
United States, Texas
Novartis Investigative Site Recruiting
San Antonio, Texas, United States, 78229
Novartis Investigative Site Not yet recruiting
Sherman, Texas, United States, 75090
Novartis Investigative Site Recruiting
Tyler, Texas, United States, 75702
Novartis Investigative Site Recruiting
Waco, Texas, United States, 76712
United States, Washington
Novartis Investigative Site Recruiting
Vancouver, Washington, United States, 98684
Novartis Investigative Site Recruiting
Yakima, Washington, United States, 98902
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT01294579     History of Changes
Other Study ID Numbers: 114612 
Study First Received: February 3, 2011
Last Updated: March 8, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Non-Hodgkin's Lymphoma
Ofatumumab
Relapsed
Rituximab
Bendamustine

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Bendamustine Hydrochloride
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 21, 2016