Patients With Relapsed or Refractory Diffuse Large B Cell Non Hodgkin Lymphomas

This study has been terminated.
(Study terminated due to slow acrual)
Sponsor:
Collaborator:
University of Illinois at Chicago
Information provided by (Responsible Party):
Dr. Sigrun Hallmeyer, Oncology Specialists, S.C.
ClinicalTrials.gov Identifier:
NCT01078922
First received: February 23, 2010
Last updated: July 2, 2014
Last verified: July 2014
  Purpose

This is a phase II open label study that looks at the efficacy and toxicity of Ofatumumab monotherapy in patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL). Patients will receive weekly infusions of Ofatumumab of 1000 mg each for 8 weeks (induction phase) followed by continuing the study drugs every other week in subsequent cycles (maintenance phase). Each 4 weeks of therapy will be calculated as one cycle. Treatment will continue until disease progression, toxicity, patient's withdrawal, or investigator's discretion.


Condition Intervention Phase
Non-Hodgkin Lymphomas
Drug: Ofatumumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Open-label Study of Single Agent Ofatumumab in Patients With Relapsed and/or Refractory Diffuse Large B Cell Non Hodgkin Lymphomas

Resource links provided by NLM:


Further study details as provided by Oncology Specialists, S.C.:

Primary Outcome Measures:
  • Overall Response (OR) [ Time Frame: evaluated every 2 months up to 80 weeks ] [ Designated as safety issue: No ]

    OR = # of patients with a Complete Response (CR) plus # of patients with a Partial Response (PR) divided by the total # of evaluable patients.

    A CR is defined as:

    1. Disappearance of all disease.
    2. If nodal masses that Positron Emission Tomography (PET)- positive prior to therapy; they must be PET negative
    3. If the nodal masses were Variably or PET negative; they must regress to normal.
    4. No palpable liver or spleen
    5. Palpable nodal masses are no longer palpable
    6. Negative bone marrow biopsy

    A PR is defined as:

    1. Regression of measurable disease and no new sites of disease.
    2. > 50% decrease in Sum of Product of Diameters (SPD) of up to 6 largest masses with no increase in the size of other nodes. If the nodal masses were PET positive prior to therapy then PET positive at previously involved sites is allowed. If they were Variably or PET negative then regression on CT is required.
    3. No increase in the size of the liver or spleen


Secondary Outcome Measures:
  • Overall Clinical Benefit (OCB) [ Time Frame: Evaluated every 2 cycles (every 2 months), up to 80 weeks ] [ Designated as safety issue: No ]

    OCB = # patients with a CR + # of patients with a PR + # patients with Stable Disease (SD) divided by the number of evaluable patients CR and PR is defined in Outcome Measure #1

    SD is defined as:

    1. Failure to attain CR/PR or Progressive Disease (PD)
    2. PET remains positive.

    PD is defined as:

    1. Any new lesion > 1.5 cm in longest axis
    2. An increase 50% or more of previously involved sites from nadir
    3. 50% increase in SPD of more than one node or 50% increase in the longest diameter of a previously identified node that is > 1 cm in shortest axis
    4. PET remains positive if it was positive before therapy.


Enrollment: 11
Study Start Date: February 2010
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ofatumumab
The first dose administered of ofatumumab should be 300 mg to minimize infusion reactions. The initial rate of the first infusion of 1000 mg ofatumumab (0.3mg/ml) should be 12ml/h. If no infusion reactions occur the infusion rate should be increased every 30 minutes, to a maximum of 400 ml/h. If this schedule is followed, the infusion duration will be approximately 4.5 hours.
Drug: Ofatumumab
The first dose administered of ofatumumab should be 300 mg to minimize infusion reactions. The initial rate of the first infusion of 1000 mg ofatumumab (0.3mg/ml) should be 12ml/h. If no infusion reactions occur the infusion rate should be increased every 30 minutes, to a maximum of 400 ml/h. If this schedule is followed, the infusion duration will be approximately 4.5 hours.
Other Name: OFT113588

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  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Relapsed and/or refractory DLBCL,not HSCT candidates. Pts must have failed standard of care (SOC) therapy w/rituximab plus CHOP or its equivalent & not considered hematopoietic stem cell transplant (HSCT) candidates based on investigator's discretion
  • Pts must have measurable disease radiographically on CT and/or PET scans and/or bone marrow biopsy.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Age ≥18 years. No upper limit of age
  • Life expectancy of 6 months or more based on investigator's best estimate.
  • Pts able to read, understand, & sign informed consent
  • Evidence of CD20 positivity in treated pts, using flow or immunohistochemistry.
  • Pts will be stratified based on bulk of disease (bulk defined as any area w/ more than 5cm in greatest dimension)
  • Pts must agree to an acceptable form of birth control

Exclusion Criteria:

  • Other histologies of non-Hodgkin's lymphoma (NHL)
  • Known central nervous system (CNS) involvement with NHL
  • Known HIV positive status
  • Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment.
  • Corticosteroid use is allowed as long as it is for non-lymphoma related causes such as rheumatoid arthritis and chronic obstructive pulmonary disease (COPD).
  • Pts w/prior malignancies are allowed as long as they are in remission & their last treatment for such malignancy is 2 years prior to enrollment or more. Pts w/non-melanoma skin cancers that have received adequate therapy prior to enrollment & women w/history of cervical cancers are allowed.
  • Significant concurrent uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurologic, cerebral, or psychiatric disease.
  • Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease per the investigator's assessment).
  • Adequate bone marrow function by virtue of having Platelets >50,000/ul & absolute neutrophil count (ANC) >1000/ul is required unless low counts are attributed to diffuse bone marrow infiltration with NHL as documented with a bone marrow biopsy exam.
  • Pts with creatinine >2.0 times the upper limit of normal will be excluded unless they have a normal creatinine clearance-estimated or measure 12 or 24 hour creatinine clearance of <60 mL/min
  • Pts w/total bilirubin >1.5 times upper limit of normal will be excluded, unless due to DLBCL involvement of liver or a known history of Gilbert's disease.
  • Pts with aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/Alkaline phosphatase (Alk Phos) >2.5 times upper limit of normal
  • Previous tx with Ofatumumab
  • Prior exposure to an investigational agent within 4-weeks from starting Ofatumumab
  • History of significant cerebrovascular disease or event w/significant symptoms or sequelae
  • Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to randomization, congestive heart failure (NYHA III-IV), & arrhythmia unless controlled by therapy, w/exception of extra systoles or minor conduction abnormalities.
  • Positive serology for hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive & regardless of HBsAb status, a HB DNA test will be performed and if positive the subject to be excluded. Note: If HBcAb positive and HBsAb positive, which is indicative of a past infection, subject can be included
  • Positive serology for hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the result.
  • Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at screening, including women whose last menstrual period was less than 1 year prior to screening, unable or unwilling to use adequate contraception from study start to 1 year after the last dose of protocol therapy. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence.
  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: NCT01078922

Locations
United States, Illinois
University of Illinois at Chicago
Chicago, Illinois, United States, 60612
Oncology Specialists, S.C
Niles, Illinois, United States, 60714
Oncology Specialists, S.C.
Park Ridge, Illinois, United States, 60068
Sponsors and Collaborators
Oncology Specialists, S.C.
University of Illinois at Chicago
Investigators
Principal Investigator: Chadi Nabhan, MD Oncology Specialists, S.C.
  More Information

No publications provided

Responsible Party: Dr. Sigrun Hallmeyer, Principal Investigator, Oncology Specialists, S.C.
ClinicalTrials.gov Identifier: NCT01078922     History of Changes
Other Study ID Numbers: OFT113588 (0908)
Study First Received: February 23, 2010
Results First Received: April 1, 2014
Last Updated: July 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Oncology Specialists, S.C.:
ofatumumab diffuse B cell non hodgkins lymphoma DLBCL
refractory DLBCL
relapsed DLBCL

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

ClinicalTrials.gov processed this record on July 26, 2014