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 is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by SCRI Development Innovations, LLC
Sponsor:
Collaborators:
GlaxoSmithKline
Cephalon
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT01626352
First received: June 20, 2012
Last updated: August 14, 2014
Last verified: August 2014
  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: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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:
  • Evaluate Complete Response Rate in Stage III-IV DLBCL [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Duration of response [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 64
Study Start Date: August 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: January 2015 (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 (see Figure 1).
Drug: Bendamustine
Patients will receive as an IV infusion bendamustine 90 mg/m^2 Days 1 and 2 of Cycles 1 through 6 and ofatumumab 1000-mg IV Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2 through 6(a cycle is defined as 21 days in length).
Other Name: Treanda
Drug: Ofatumumab
Patients will receive as an IV infusion bendamustine 90 mg/m^2 Days 1 and 2 of Cycles 1 through 6 and ofatumumab 1000-mg IV Days 1 and 8 during Cycle 1 only and on Day 1 of Cycles 2 through 6(a cycle is defined as 21 days in length).

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

Ages Eligible for Study:   70 Years and older
Genders Eligible for Study:   Both
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
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: NCT01626352

Contacts
Contact: Ian Flinn, MD, PhD 1-877-691-7274 asksarah@scresearch.net
Contact: Trials Info 1-877-691-7274 asksarah@scresearch.net

Locations
United States, Florida
Florida Cancer Specialists-South Recruiting
Fort Myers, Florida, United States, 33916
Woodlands Medical Specialists Recruiting
Pensacola, Florida, United States, 32503
Florida Cancer Specialists North Recruiting
St. Petersburg, Florida, United States, 33705
Space Coast Cancer Center Recruiting
Titusville, Florida, United States, 32796
United States, Indiana
RHHP/Hope Cancer Center Recruiting
Terre Haute, Indiana, United States, 47802
Providence Medical Group Recruiting
Terre Haute, Indiana, United States, 47802
United States, Michigan
Grand Rapids Oncology Program Recruiting
Grand Rapids, Michigan, United States, 49503
United States, New Hampshire
Portsmouth Regional Hospital Recruiting
Portsmouth, New Hampshire, United States, 03801
United States, Oklahoma
Cancer Centers of Southwest Oklahoma Recruiting
Lawton, Oklahoma, United States, 73505
Oklahoma University Recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Tennessee Oncology-Chattanooga Recruiting
Chattanooga, Tennessee, United States, 37404
Contact: askSARAH       askSARAH@scresearch.net   
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37023
Sponsors and Collaborators
SCRI Development Innovations, LLC
GlaxoSmithKline
Cephalon
Investigators
Study Chair: Ian Flinn, MD, PhD SCRI Development Innovations, LLC
  More Information

No publications provided

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT01626352     History of Changes
Other Study ID Numbers: SCRI LYM 75
Study First Received: June 20, 2012
Last Updated: August 14, 2014
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on September 22, 2014