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Study of Bendamustine and Ofatumumab in Elderly Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma Who Are Poor Candidates for R-CHOP Chemotherapy

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: NCT01626352
Recruitment Status : Completed
First Posted : June 22, 2012
Results First Posted : October 18, 2017
Last Update Posted : November 22, 2017
Sponsor:
Collaborators:
Novartis
GlaxoSmithKline
Cephalon
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Tracking Information
First Submitted Date  ICMJE June 20, 2012
First Posted Date  ICMJE June 22, 2012
Results First Submitted Date  ICMJE September 15, 2017
Results First Posted Date  ICMJE October 18, 2017
Last Update Posted Date November 22, 2017
Actual Study Start Date  ICMJE October 2012
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 19, 2017)
Number of Patients With a Complete Response [ Time Frame: 18 months ]
Disease response assessments will be performed using the International Working Group (IMW)-revised response criteria for malignant lymphoma (Cheson 2007). Complete response requires a disappearance of all evidence of disease.
Original Primary Outcome Measures  ICMJE
 (submitted: June 21, 2012)
Evaluate Complete Response Rate in Stage III-IV DLBCL [ Time Frame: 18 months ]
To evaluate the complete response rate (CRR) in patients with newly diagnosed Stage III-IV DLBCL considered poor candidates for R-CHOP therapy treated with the combination of ofatumumab and bendamustine.
Change History Complete list of historical versions of study NCT01626352 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2017)
  • Duration of Response [ Time Frame: After cycles 3 and 6 of each 21-day cycle and every 3 months thereafter until disease progression or relapse from complete response for up to 38 months ]
    Defined as the time from date of first documented confirmed response to date of disease progression or relapse from complete response as defined by the International Working Group (IMW)-revised response criteria for malignant lymphoma (Cheson 2007). This criteria categorizes the response of a patient's tumor to treatment as Complete Response (CR): the disappearance of all disease evidence; Partial Response (PR): regression of measurable disease and no new sites; Stable Disease (SD): less than a PR but not progressive disease (PD); Relapsed Disease or PD: Any new lesion or increase by ≥ 50% of previously involved sites from nadir. Patients who are alive and free from disease progression will be censored at the date of last tumor assessment. Patients who begin further anticancer therapy prior to disease progression will be censored at the date of last tumor assessment prior to the start date of the anticancer therapy.
  • Time to Progression (TTP) [ Time Frame: After cycles 3 and 6 of each 21-day cycle, and every 3 months thereafter until progression or relapse from complete response for up to 40 months ]
    Defined as the time from date of first treatment to the date of first documented disease progression or relapse from complete response as defined by the International Working Group (IMW)-revised response criteria for malignant lymphoma (Cheson 2007). This criteria categorizes the response of a patient's tumor to treatment as Complete Response (CR): the disappearance of all disease evidence; Partial Response (PR): regression of measurable disease and no new sites; Stable Disease (SD): less than a PR but not progressive disease (PD); Relapsed Disease or PD: Any new lesion or increase by ≥ 50% of previously involved sites from nadir.
  • Overall Survival (OS) [ Time Frame: every 3 cycles during treatment and every 3 months thereafter until progression or death from any cause, projected 18 months ]
    Defined as the time from Day 1 of study drug administration to date of death from any cause.
  • Overall Response (OR) [ Time Frame: after cycles 3 and 6 of each 21-day cycle, and every 3 months thereafter, projected 18 months ]
    Overall response is the number of patients with observed complete or partial response (CR or PR) as assessed using the International Working Group (IMW) revised response criteria for malignant lymphoma (Cheson 2007). Complete response requires disappearance of all evidence of disease. Partial response requires regression of measurable disease and no new sites.
  • Number of Patients With Treatment-Related Adverse Events (AEs) as a Measure of Safety [ Time Frame: after cycles 3 and 6 of each 21-day cycle, and up to 30 days after last dose, projected 24 weeks ]
    A treatment-related adverse event was any untoward medical occurrence in a participant which was considered to have a relationship with the study drug (suspected to be possibly or probably related to the study drug per the Investigator's assessment). Adverse events were evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
  • Progression-free Survival [ Time Frame: After cycles 3 and 6 of each 21-day cycle, and every 3 months thereafter until progression or relapse from complete response for up to 40 months ]
    Defined as the time from first treatment until objective tumor progression, relapse from complete response, or death from any cause. Tumor response is defined by the International Working Group (IMW)-revised response criteria for malignant lymphoma (Cheson 2007). This criteria categorizes the response of a patient's tumor to treatment as Complete Response (CR): the disappearance of all disease evidence; Partial Response (PR): regression of measurable disease and no new sites; Stable Disease (SD): less than a PR but not progressive disease (PD); Relapsed Disease or PD: Any new lesion or increase by ≥ 50% of previously involved sites from nadir. Patients who are alive and free from disease progression will be censored at the date of last tumor assessment.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 21, 2012)
  • Duration of response [ Time Frame: 18 Months ]
    To assess the duration of response in patients with previously untreated DLBCL receiving ofatumumab and bendamustine who are poor candidates for R-CHOP therapy
  • Time to Progression (TTP) [ Time Frame: 18 months ]
    To assess the time to progression (TTP) in patients with previously untreated DLBCL receiving ofatumumab and bendamustine who are poor candidates for R-CHOP therapy
  • Safety profile of study treatment [ Time Frame: 18 Months ]
    To assess the safety profile of study treatment in patients with previously untreated DLBCL receiving ofatumumab and bendamustine who are poor candidates for R-CHOP therapy
  • Overall Survival (OS) [ Time Frame: 18 Months ]
    To assess the overall survival (OS) in patients with previously untreated DLBCL receiving ofatumumab and bendamustine who are poor candidates for R-CHOP therapy
  • Overall response rate (ORR) [ Time Frame: 18 Months ]
    To assess the overall response rate (ORR) in patients with previously untreated DLBCL receiving ofatumumab and bendamustine who are poor candidates for R-CHOP therapy
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Bendamustine and Ofatumumab in Elderly Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma Who Are Poor Candidates for R-CHOP Chemotherapy
Official Title  ICMJE Phase II Study of Bendamustine and Ofatumumab in Elderly Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma Who Are Poor Candidates for R-CHOP Chemotherapy
Brief Summary This is a single-arm, Phase II study designed to enroll and treat up to 64 patients. All patients in this study will receive ofatumumab and bendamustine as an IV infusion for 6 cycles (a cycle is defined as 21 days in length). Patients will receive as an IV infusion bendamustine Days 1 and 2 of Cycles 1 through 6 and ofatumumab Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2 through 6.
Detailed Description While R-CHOP has improved survival and is considered standard of care for patients with DLBCL, the toxicities associated with R-CHOP are substantial in the elderly population. This is one of several reasons the outcome of older patients is worse than the corresponding younger patients. Bendamustine is an alkylating agent which causes intra- and inter-strand cross-links between DNA bases. Ofatumumab is a fully human anti-CD 20 antibody well tolerated by elderly patients. Ofatumumab targets a novel epitope of the CD20 molecule on B cells and remains on the cell surface twice as long as rituximab. The combination of both agents allows for a potentially efficacious, less toxic regimen.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Diffuse Large B-Cell Lymphoma
Intervention  ICMJE
  • Drug: Bendamustine
    Patients will receive as an IV infusion bendamustine 90 mg/m^2 Days 1 and 2 of Cycles 1 through 6.
    Other Name: Treanda
  • Drug: Ofatumumab
    Patients will receive as an IV infusion ofatumumab 1000-mg IV Days 1 and 8 during Cycle 1 only, and on Day 1 of Cycles 2 through 6
Study Arms  ICMJE Experimental: Bendamustine/Ofatumumab
All patients in this study will receive ofatumumab and bendamustine as an IV infusion for 6 cycles (a cycle is defined as 21 days in length). Patients will receive as an IV infusion of bendamustine Days 1 and 2 of Cycles 1-6, ofatumumab Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2-6.
Interventions:
  • Drug: Bendamustine
  • Drug: Ofatumumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 19, 2017)
22
Original Estimated Enrollment  ICMJE
 (submitted: June 21, 2012)
64
Actual Study Completion Date  ICMJE April 2017
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histologically confirmed CD20-positive DLBCL.
  2. Newly diagnosed, stage III-IV DLBCL considered poor candidates for R-CHOP.
  3. Age >=70 years
  4. At least one of the following criteria:

    • ECOG PS 2
    • Cardiac compromise precluding anthracycline therapy
    • Previous anthracycline therapy for other malignancy precluding further anthracycline therapy.
    • Severe coexisting medical problems
    • General frailty
  5. ECOG 0-2
  6. Measurable disease with at least one bidimensional lymph node or tumor mass >1.5 cm in the longest diameter that can be followed for response as a target lesion as measured by CT
  7. Patients must be HBV sAg and HBV cAb negative within 6 weeks of screening.
  8. Patient must understand and voluntarily sign the IRB-approved informed consent.
  9. Life expectancy >= 3 months
  10. Laboratory parameters:

    • Absolute neutrophil count >=1,000 cells/mm3
    • Platelet count >=75,000 cells/mm3
    • Hemoglobin >=8 g/dL
    • Creatinine <=2.0 mg/dL or Creatinine Clearance >= 40 mL/min (calculated or 24 hour urine sample)
    • AST/SGOT <=2.0 x ULN (<=5.0 x ULN if secondary to lymphoma)
    • ALT/SGPT <=2.0 x ULN (<=5.0 x ULN if secondary to lymphoma)
    • Bilirubin level of <2.0 mg/dL unless secondary to Gilbert's disease (or pattern consistent with Gilbert's)

Exclusion Criteria:

  1. Patients with active/symptomatic central nervous system (CNS) involvement based on clinical evaluation by lumbar puncture, PET, CT or MRI.
  2. Known sensitivity to bendamustine or any component of bendamustine.
  3. Known anaphylaxis or sensitivity to ofatumumab.
  4. Major surgery within 28 days of Cycle 1, Day 1. Patients undergoing minor surgery within 7 days of Cycle 1, Day 1. (no wait needed for port placement)
  5. Prior chemotherapy, immunotherapy, or irradiation for lymphoma.
  6. Prior use of investigational anti-cancer agents for lymphoma.
  7. HIV-related lymphoma.
  8. Known active HIV or HCV infection, or known seropositivity for HIV, or current or chronic HBV or HCV infection. HBV test required at screening or a negative result within 6 weeks of screening.
  9. Concurrent active or history of other malignancies, except non-melanoma skin cancer or carcinoma in situ of cervix or breast. Patients with previous malignancies are eligible provided they have been treated with curative intent and disease free for >= 1 year.
  10. Serious (grade 3-4), active, intercurrent infection requiring therapy, or deep seated or systemic mycotic infections.
  11. Myocardial infarction within 6 months prior to registration or New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or significant conduction system abnormalities, in the judgment of the Investigator.
  12. Concurrent uncontrolled serious medical or psychiatric conditions likely to interfere with participation in this clinical study, in the judgment of the Investigator
  13. Patients who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
  14. Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study.
  15. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient.
  16. Male patients unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 70 Years and older   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01626352
Other Study ID Numbers  ICMJE SCRI LYM 75
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party SCRI Development Innovations, LLC
Study Sponsor  ICMJE SCRI Development Innovations, LLC
Collaborators  ICMJE
  • Novartis
  • GlaxoSmithKline
  • Cephalon
Investigators  ICMJE
Study Chair: Ian Flinn, MD, PhD SCRI Development Innovations, LLC
PRS Account SCRI Development Innovations, LLC
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP