Clinical Trials /

Ipilimumab and Rituximab in Treating Patients With Relapsed or Refractory B-cell Lymphoma

NCT01729806

Description:

This partially randomized phase I trial studies the side effects and best dose of ipilimumab when given together with rituximab in treating patients with B-cell lymphoma that has returned or has not responded to treatment. Monoclonal antibodies, such as ipilimumab and rituximab, may interfere with the ability of cancer cells to grow and spread.

Related Conditions:
  • Mature B-Cell Lymphoma/Leukemia
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Ipilimumab</span> and <span class="go-doc-concept go-doc-intervention">Rituximab</span> in Treating Patients With Relapsed or Refractory B-Cell Lymphoma

Title

  • Brief Title: Ipilimumab and Rituximab in Treating Patients With Relapsed or Refractory B-Cell Lymphoma
  • Official Title: A Phase I Study of Ipilimumab in Combination With Rituximab in Patients With Relapsed/Refractory CD20+ B-Cell Lymphoma
  • Clinical Trial IDs

    NCT ID: NCT01729806

    ORG ID: NCI-2012-02213

    NCI ID: NCI-2012-02213

    Trial Conditions

    Recurrent B-Cell Non-Hodgkin Lymphoma

    Refractory B-Cell Non-Hodgkin Lymphoma

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    This partially randomized phase I trial studies the side effects and best dose of ipilimumab
    when given together with rituximab in treating patients with B-cell lymphoma that has
    returned or has not responded to treatment. Monoclonal antibodies, such as ipilimumab and
    rituximab, may interfere with the ability of cancer cells to grow and spread.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To determine a recommended phase II dose for ipilimumab in combination with rituximab.

    SECONDARY OBJECTIVES:

    I. To obtain preliminary information on the effect of adding ipilimumab to rituximab in
    regard to: immune response; clinical anti-tumor response/overall remission rate (ORR)
    (complete remission + partial remission); progression free survival (PFS).

    OUTLINE: This is a dose-escalation study of ipilimumab followed by a randomized study.

    PART I:

    INDUCTION: Patients receive ipilimumab intravenously (IV) over 90 minutes once every 3 weeks
    for 12 weeks and rituximab IV over 2-6 hours once weekly for 4 weeks.

    MAINTENANCE: Patients receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours
    once every 12 weeks for up to 1 year.

    PART II: Patients are randomized to 1 of 2 treatment arms.

    ARM A: Patients receive rituximab IV over 2-6 hours once weekly in weeks 1-4 and ipilimumab
    IV over 90 minutes once weekly in weeks 1, 4, 7, and 10. Patients then receive ipilimumab IV
    over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year in the
    absence of disease progression or unacceptable toxicity.

    ARM B: Patients receive rituximab IV over 2-6 hours once weekly in weeks 1-4 and ipilimumab
    IV over 90 minutes once weekly in weeks 3, 6, 9, and 12. Patients then receive ipilimumab IV
    over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year in the
    absence of disease progression or unacceptable toxicity.

    After completion of study treatment, patients are followed up for 12 months.

    Trial Arms

    Name Type Description Interventions
    Arm A (ipilimumab and rituximab) Experimental Patients receive rituximab IV over 2-6 hours once weekly in weeks 1-4 and ipilimumab IV over 90 minutes once weekly in weeks 1, 4, 7, and 10. Patients then receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
    Arm B (ipilimumab and rituximab) Experimental Patients receive rituximab IV over 2-6 hours once weekly in weeks 1-4 and ipilimumab IV over 90 minutes once weekly in weeks 3, 6, 9, and 12. Patients then receive ipilimumab IV over 90 minutes and rituximab IV over 2-6 hours once every 12 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

    Eligibility Criteria

    Inclusion Criteria:

    - Previously treated, histologically confirmed cluster of differentiation (CD)20+ B
    cell lymphoma; bone marrow biopsies as the sole means of diagnosis are not
    acceptable, but they may be submitted in conjunction with nodal biopsies or extra
    nodal biopsies; fine needle aspirates are not acceptable

    - All patients must be informed of the investigative nature of the clinical trial and
    give written informed consent in accordance with institutional and federal guidelines

    - Able to adhere to the study visit schedule and other protocol requirements

    - Karnofsky >= 70%

    - Life expectancy expected to be greater than 3 months

    - Leukocytes >= 3,000/mcL

    - Absolute neutrophil count >= 1,000/mcL

    - Platelets >= 50,000/mcL

    - Total bilirubin =< 2.0 x institutional upper limit of normal

    - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
    [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
    =< 2.5 x institutional upper limit of normal

    - Serum creatinine =< 2.0 x upper limit of normal or calculated creatinine clearance >=
    30 ml/min/1.73 M^2 by the modified Cockcroft and Gault formula or creatinine
    clearance >= 30 mL/min obtained from a 24-hour urine collection

    - At least one measurable lesion according to international workshop lymphoma response
    criteria (Cheson 2007); there must be measurable lymphadenopathy to follow with
    serial exam and/or imaging

    - All previous cancer therapy, including radiation, hormonal therapy and surgery, must
    have been discontinued at least 4 weeks prior to treatment in this study

    - Patients must have evidence of progression of disease during or after last treatment

    - Submission of original biopsy for review and verification by participating center
    hematopathologist

    - Disease free of prior malignancies for >= 3 years with exception of currently treated
    basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix
    or breast

    Exclusion Criteria:

    - Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
    nitrosoureas or mitomycin C) prior to entering the study or those who have not
    recovered from adverse events due to agents administered more than 4 weeks earlier

    - Patients with a history of prior treatment with ipilimumab

    - Patients with a history of prior treatment with an anti-programmed death (PD) 1
    antibody, CD137 agonist or other immune activating therapy such as anti-CD 40
    antibody are excluded unless 5 half-lives of the agent (minimum of 8 weeks) have
    intervened since the therapy; patients who have received prior vaccine therapy are
    eligible

    - Patients who are receiving any other investigational agents

    - Autoimmune disease: patients with a history of inflammatory bowel disease, including
    ulcerative colitis and Crohn's disease, are excluded from this study, as are patients
    with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic
    progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune
    vasculitis [e.g., Wegener's granulomatosis]); central nervous system (CNS) or motor
    neuropathy considered of autoimmune origin (e.g. Guillain-Barre syndrome and
    myasthenia gravis, multiple sclerosis)

    - Patients with known immune impairment who may be unable to respond to anti-cytotoxic
    T-lymphocyte antigen 4 (CTLA 4) antibody

    - Patients with known brain metastases are excluded

    - History of allergic reactions attributed to compounds of similar chemical or biologic
    composition to rituximab

    - Patients on systemic corticosteroids (except for patients on stable doses of hormone
    replacement therapy such as hydrocortisone), or other immunosuppressants (e.g.,
    infliximab, mycophenolate mofetil) are excluded

    - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
    infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
    arrhythmia, or psychiatric illness/social situations that would limit compliance with
    study requirements

    - Patients with chronic human immunodeficiency virus (HIV), hepatitis B or hepatitis C
    infections are excluded

    - Pregnant women are excluded from this study

    - HIV-positive patients on combination antiretroviral therapy are ineligible

    - Rituximab within six weeks

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Incidence of toxicities according to the Common Terminology Criteria for Adverse Events version 4

    Secondary Outcome Measures

    Clinical anti-tumor response (complete response and partial response as per international workshop lymphoma response criteria [Cheson 2007])

    Immune response as measured by the frequency of activated T-cells, absolute lymphocyte count, antibody dependent cell-mediated cytotoxicity, and kinetics and magnitude of B-cell depletion

    Progression-free survival

    Trial Keywords