Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 100 of 315 for:    BENDAMUSTINE

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01294579
Recruitment Status : Completed
First Posted : February 11, 2011
Results First Posted : August 9, 2018
Last Update Posted : August 9, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this phase II open label study was is to evaluate the safety and efficacy of ofatumumab and bendamustine followed by maintenance ofatumumab in subjects with indolent B-NHL who had 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, would have been enrolled (34 in Stage 1 and 19 in Stage 2). Subjects should have had 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 relapsed or have had disease progression following response to prior rituximab-based therapy 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) were 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 received ofatumumab 1000 mg IV every 2 months for 2 years.

Condition or disease Intervention/treatment Phase
Lymphoma, Non-Hodgkin Biological: Ofatumumab Drug: Bendamustine Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Masking: None (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
Actual Study Start Date : May 17, 2011
Actual Primary Completion Date : December 20, 2016
Actual Study Completion Date : December 20, 2016


Arm Intervention/treatment
Experimental: ofatumumab and bendamustine

1000 mg intravenous (IV) on day 1 of each cycle (cycles 1-6) for induction phase and 1000 mg IV every 2 months for 2 years.

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

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)




Primary Outcome Measures :
  1. Complete Remission (CR) Rate of Induction Therapy After Cycle 6 (28 Days) (FAS) [ Time Frame: Baseline up to 24 weeks ]
    Complete response (CR) included all of the following: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. All target nodes had to have regressed to ≤ 1.5cm in the longest diameter. Non-measureable nodes 1.1 to 1.5cm in the longest diameter and >1cm in the short axis at baseline had to regress to ≤ 1cm in the short axis by visual estimation; enlarged spleen or liver (with nodules) must have returned to normal size and nodules disappeared and if bone marrow was involved, infiltrate had to have cleared on repeat biopsy sample. CR was not valid without imaging data. The corresponding 2-sided 95% exact confidence interval (CI) of the response rate was estimated by the Clopper-Pearson method.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) During Induction Phase After Cycle 6 (FAS) [ Time Frame: Baseline up to 24 weeks ]
    The overall response = CR (defined in Primary Outcome) + Partial Response (PR) which required all of the following: > or = to 50% decrease from baseline in target nodules; > or = to 50% decrease in hepatic/splenic nodules and no increase in liver or spleen size; no unequivocal progression in non-target lestions; no new sites of disease.

  2. Conversion Rate of Partial Response in Induction Phase to Complete Response With Maintenance Ofatumumab (FAS) [ Time Frame: Partial response in induction phase up to 24 weeks ]
    Rate of conversion from PR in the Induction phase, to CR with maintenance ofatumumab in subjects who have a PR with induction therapy with ofatumumab and bendamustine

  3. Percentage of Participants With Progression Free Survival (PFS) up to 30 Months (FAS) [ Time Frame: Baseline up to approximately 30 months ]
    Progression free survival (PFS) is defined as the interval between first treatment and disease progression or death due to any cause. PFS criteria: A previously normal node (≤ 1.5 x ≤ 1.0cm), including nodes that were not previously visible, must increase to >2.0 x ≥ 1.5cm; ≥ 50% increase from nadir in the PPD of any target node. The long axis must increase by at least 5 mm and to >2.0cm.; ≥ 50% increase from nadir in the long axis of any target node. The long axis must increase by at least 5 mm and to >2.0 cm.; ≥ 50% increase from nadir in the SPD of target nodes and at least one node should have a long axis >1.5 cm.

  4. Kaplan-Meier Estimates of Progression Free Survival up to 30 Months (FAS) [ Time Frame: Baseline up to approximately 30 months ]
    Progression Free Survival (PFS) is defined as the interval between first treatment and disease progression or death due to any cause. PFS events: progression documented between scheduled visits, death before first PD assessment (or death at baseline or prior to any adequate assessments), death between adequate assessment visits. For the PFS analysis, the survival function was estimated using Kaplan-Meier estimates.

  5. 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: up to 30 months ]
    Due to recruitment issues, this data analysis was not done per changes in planned analysis. This data was only presented as patient listings. The statistical analysis plan was modified to indicate that Pharmacokinetic/Pharmacodynamic exploratory analyses were not done.

  6. All Deaths by Preferred Term (Safety Set) up to Approximately 30 Months [ Time Frame: Baseline up to approximately 30 months ]
    Deaths were collected and were considered to be an on treatment death up to 60 days post treatment.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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 was 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, that requiried 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 had 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 had 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 have been on any prohibited medications.
  • Subjects who had received prior bendamustine were eligible if they had 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 had transformed to aggressive lymphoma. Subjects suspicious for transformation should have undergone 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 were NOT eligible for this study.
  • Rituximab-refractory disease, defined as failure to have responded 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 was 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 had to have been performed and if positive the subject will be excluded. If HBV DNA is negative, subject may be included but must have undergone HBV DNA monitoring. Prophylactic antiviral therapy may have been 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 were 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01294579


Locations
Layout table for location information
United States, Arizona
Novartis Investigative Site
Chandler, Arizona, United States, 85224
United States, California
Novartis Investigative Site
Burbank, California, United States, 91505
Novartis Investigative Site
Fresno, California, United States, 93720
Novartis Investigative Site
Oxnard, California, United States, 93030
United States, Colorado
Novartis Investigative Site
Aurora, Colorado, United States, 80045
United States, Florida
Novartis Investigative Site
Orange Park, Florida, United States, 32073
United States, Massachusetts
Novartis Investigative Site
Burlington, Massachusetts, United States, 01805
United States, Nebraska
Novartis Investigative Site
Omaha, Nebraska, United States, 68198-9200
United States, Nevada
Novartis Investigative Site
Las Vegas, Nevada, United States, 89169
United States, North Carolina
Novartis Investigative Site
Cary, North Carolina, United States, 27518
Novartis Investigative Site
Charlotte, North Carolina, United States, 28204
Novartis Investigative Site
Raleigh, North Carolina, United States, 27607
United States, Ohio
Novartis Investigative Site
Kettering, Ohio, United States, 45429
United States, Oregon
Novartis Investigative Site
Eugene, Oregon, United States, 97401
United States, South Carolina
Novartis Investigative Site
Charleston, South Carolina, United States, 29414
Novartis Investigative Site
Greenville, South Carolina, United States, 29601
United States, Texas
Novartis Investigative Site
San Antonio, Texas, United States, 78229
Novartis Investigative Site
Sherman, Texas, United States, 75090
Novartis Investigative Site
Tyler, Texas, United States, 75702
Novartis Investigative Site
Waco, Texas, United States, 76712
United States, Washington
Novartis Investigative Site
Vancouver, Washington, United States, 98684
Novartis Investigative Site
Yakima, Washington, United States, 98902
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01294579     History of Changes
Other Study ID Numbers: 114612
First Posted: February 11, 2011    Key Record Dates
Results First Posted: August 9, 2018
Last Update Posted: August 9, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Non-Hodgkin's Lymphoma
Ofatumumab
Relapsed
Rituximab
Bendamustine
Additional relevant MeSH terms:
Layout table for MeSH terms
Bendamustine Hydrochloride
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Ofatumumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action