Clinical Trials /

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

NCT01294579

Description:

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.

Related Conditions:
  • Non-Hodgkin Lymphoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Ofatumumab</span> and <span class="go-doc-concept go-doc-intervention">Bendamustine</span> Followed by Maintenance <span class="go-doc-concept go-doc-intervention">Ofatumumab</span> for <span class="go-doc-concept go-doc-intervention">Rituximab</span> Relapsed Indolent B-cell Non-Hodgkin's Lymphoma (B-NHL)

Title

  • Brief Title: Ofatumumab and Bendamustine Followed by Maintenance Ofatumumab for Rituximab Relapsed Indolent B-cell Non-Hodgkin's Lymphoma (B-NHL)
  • 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
  • Clinical Trial IDs

    NCT ID: NCT01294579

    ORG ID: 114612

    Trial Conditions

    Lymphoma, Non-Hodgkin

    Trial Interventions

    Drug Synonyms Arms
    Bendamustine Open Label Single Arm

    Trial Purpose

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

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Open Label Single Arm Experimental ofatumumab and Bendamustine Bendamustine

    Eligibility 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 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,
    requiring 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 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 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 be on any prohibited medications.

    - Subjects who have received prior bendamustine are eligible if they 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 has
    transformed to aggressive lymphoma. Subjects suspicious for transformation should
    undergo 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/l are defined by 2008 International Workshop on Chronic
    Lymphocytic Leukemia (IWCLL) criteria to have CLL; such patients are NOT eligible for
    this study.

    - Rituximab-refractory disease, defined as failure to respond 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 is
    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 will be performed and if positive the subject will be
    excluded. If HBV DNA is negative, subject may be included but must undergo HBV DNA
    monitoring. Prophylactic antiviral therapy may be 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 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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Complete Remission (CR) Rate of Induction Therapy

    Secondary Outcome Measures

    Overall Response Rate (PR +CR) of Induction therapy

    Conversion of PR to CR with Maintenance Ofatumumab

    Progression Free Survival (PFS)

    Number of Participants with Adverse Events as a Measure of Safety and Tolerability of Combination of Ofatumumab and Bendamustine

    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

    Trial Keywords

    Non-Hodgkin's Lymphoma

    Ofatumumab

    Rituximab

    Relapsed

    Bendamustine