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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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01626352
First Posted: June 22, 2012
Last Update Posted: October 18, 2017
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.
Collaborators:
Novartis
GlaxoSmithKline
Cephalon
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
  Purpose
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.

Condition Intervention Phase
Diffuse Large B-Cell Lymphoma Drug: Bendamustine Drug: Ofatumumab Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • 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. Complete response requires a disappearance of all evidence of disease.


Secondary Outcome Measures:
  • Duration of Response [ Time Frame: after cycles 3 and 6 of each 21-day cycle and every 3 months thereafter ]
    Defined as the time from date of first documented confirmed response to date of disease progression or relapse from complete response. 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 ]
    Defined as the time from date of first treatment to the date of first documented disease progression or relapse from complete response.

  • 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. 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 ]
    Defined as the time from first treatment until objective tumor progression, relapse from complete response, or death from any cause


Enrollment: 22
Actual Study Start Date: August 2012
Study Completion Date: April 2017
Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

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.
  Eligibility

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.


Ages Eligible for Study:   70 Years and older   (Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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): NCT01626352


Locations
United States, Florida
Florida Cancer Specialists-South
Fort Myers, Florida, United States, 33916
Woodlands Medical Specialists
Pensacola, Florida, United States, 32503
Florida Cancer Specialists North
Saint Petersburg, Florida, United States, 33705
Space Coast Cancer Center
Titusville, Florida, United States, 32796
United States, Indiana
Providence Medical Group
Terre Haute, Indiana, United States, 47802
RHHP/Hope Cancer Center
Terre Haute, Indiana, United States, 47802
United States, Michigan
Grand Rapids Oncology Program
Grand Rapids, Michigan, United States, 49503
United States, Oklahoma
Cancer Centers of Southwest Oklahoma
Lawton, Oklahoma, United States, 73505
Oklahoma University
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Tennessee Oncology-Chattanooga
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37023
Sponsors and Collaborators
SCRI Development Innovations, LLC
Novartis
GlaxoSmithKline
Cephalon
Investigators
Study Chair: Ian Flinn, MD, PhD SCRI Development Innovations, LLC
  More Information

Publications:

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT01626352     History of Changes
Other Study ID Numbers: SCRI LYM 75
First Submitted: June 20, 2012
First Posted: June 22, 2012
Results First Submitted: September 15, 2017
Results First Posted: October 18, 2017
Last Update Posted: October 18, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by SCRI Development Innovations, LLC:
Diffuse Large B-Cell Lymphoma
Ofatumumab
Bendamustine

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