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Phase I/II Study of Pembrolizumab in Patients Failing to Respond to or Relapsing After Anti-CD19 Chimeric Antigen Receptor Modified T Cell Therapy for Relapsed or Refractory CD19+ Lymphomas

NCT02650999

Description:

Single center, phase I/II trial of pembrolizumab after CTL019 for CD19+ lymphomas. Patients will have CD19+ diffuse large B-cell, follicular, or mantle cell lymphomas relapsed/refractory after CTL019. 12 total patients will be enrolled. Safety of pembrolizumab (primary endpoint) will be determined using a Bayesian monitoring rule for treatment-related adverse events causing drug discontinuation. Secondary efficacy endpoints include overall response rate and progression-free survival.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Lymphoma
  • Mantle Cell Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Study of <span class="go-doc-concept go-doc-intervention">Pembrolizumab</span> in Patients Failing to Respond to or Relapsing After Anti-CD19 Chimeric Antigen Receptor Modified T Cell Therapy for Relapsed or Refractory CD19+ Lymphomas

Title

  • Brief Title: Study of Pembrolizumab in Patients Failing to Respond to or Relapsing After Anti-CD19 Chimeric Antigen Receptor Modified T Cell Therapy for Relapsed or Refractory CD19+ Lymphomas
  • Official Title: Phase I/II Study of Pembrolizumab in Patients Failing to Respond to or Relapsing After Anti-CD19 Chimeric Antigen Receptor Modified T Cell Therapy for Relapsed or Refractory CD19+ Lymphomas
  • Clinical Trial IDs

    NCT ID: NCT02650999

    ORG ID: UPCC 46415

    Trial Conditions

    CD19+ Diffuse Large B-cell Lymphomas

    Follicular Lymphomas

    Mantle Cell Lymphomas

    Trial Interventions

    Drug Synonyms Arms
    Pembrolizumab Single Arm

    Trial Purpose

    Single center, phase I/II trial of pembrolizumab after CTL019 for CD19+ lymphomas. Patients
    will have CD19+ diffuse large B-cell, follicular, or mantle cell lymphomas
    relapsed/refractory after CTL019. 12 total patients will be enrolled. Safety of
    pembrolizumab (primary endpoint) will be determined using a Bayesian monitoring rule for
    treatment-related adverse events causing drug discontinuation. Secondary efficacy endpoints
    include overall response rate and progression-free survival.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Single Arm Experimental Pembrolizumab

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically confirmed follicular lymphoma grade 1-3A, diffuse large B cell
    lymphoma, and mantle cell lymphoma by World Health Organization 2009 classification

    - Relapsed/refractory lymphoma after CTL019 - Be willing and able to provide written
    informed consent/assent for the trial.

    - Age 18 years or older on day of signing informed consent.

    - Have baseline imaging within 6 weeks of enrollment (CT, MR or PET/CT imaging) and
    have measurable disease on physical examination or imaging studies.

    -- Not pregnant or breastfeeding

    - Any lesion 1.5 cm in long axis dimension is considered measurable. - Performance
    status of 0-2 on the ECOG Performance Scale - Demonstrate adequate organ function.

    - Absolute neutrophil count (ANC) 1,000 /mcL

    - Platelets50,000 / mcL

    - Hemoglobin 8 g/dL without transfusion or EPO dependency (within 7 days of
    assessment)

    - Serum creatinine OR Measured or calculated a creatinine clearance (aCreatinine
    clearance should be estimated per institutional standard) (GFR can also be used in
    place of creatinine or CrCl) 1.5 X upper limit of normal (ULN) OR 60 mL/min for
    subject with creatinine levels > 1.5 X institutional ULN

    - Serum total bilirubin 1.5 X ULN OR Direct bilirubin ULN for subjects with total
    bilirubin levels > 1.5 ULN.

    - AST (SGOT) and ALT (SGPT) 2.5 X ULN OR 5 X ULN for subjects with liver metastases

    - International Normalized Ratio (INR) or Prothrombin Time (PT) 1.5 X ULN unless
    subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic
    range of intended use of anticoagulants

    - Activated Partial Thromboplastin Time (aPTT) 1.5 X ULN unless subject is receiving
    anticoagulant therapy as long as PT or PTT is within therapeutic range of intended
    use of anticoagulants.

    Exclusion Criteria:

    - Is currently participating and receiving study therapy or has participated in a study
    of an investigational agent and received study therapy or used an investigational
    device within 4 weeks of the first dose of treatment. An exception will be made for
    patients who have received CTL019 on experimental protocol; these patients will be
    eligible to enroll once progression of disease or failure to respond is documented by
    clinical or radiologic assessment.

    - Patient has received intervening therapy for lymphoma after CTL019 infusion.

    - Has active cytokine release syndrome from CTL019 infusion.

    - Has a known history of active TB (Bacillus Tuberculosis). - Hypersensitivity to
    pembrolizumab or any of its excipients.

    - Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
    Day 1 or who has not recovered (i.e., Grade 1 or at baseline) from adverse events due
    to agents administered more than 4 weeks earlier. Toxicities that are disease related
    will not exclude patients.

    - Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
    within 2 weeks prior to study Day 1 or who has not recovered (i.e., Grade 1 or at
    baseline) from adverse events due to a previously administered agent. Subjects with
    Grade 2 neuropathy are an exception to this criterion and may qualify for the study.

    - Known additional malignancy that is progressing or requires active treatment.
    Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
    skin that has undergone potentially curative therapy or in situ cervical cancer.

    - Active central nervous system (CNS) metastases and/or carcinomatous meningitis.
    Subjects with previously treated brain metastases may participate provided they are
    stable (without evidence of progression by imaging for at least four weeks prior to
    the first dose of trial treatment and any neurologic symptoms have returned to
    baseline), have no evidence of new or enlarging brain metastases, and are not using
    steroids for at least 7 days prior to trial treatment.

    - Active autoimmune disease that has required systemic treatment in the past 2 years
    (i.e. use of disease modifying agents, corticosteroids or immunosuppressive drugs).
    Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
    replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
    form of systemic treatment.

    - Has known history of, or any evidence of active, non-infectious pneumonitis.

    - Active infection requiring systemic therapy.

    - History or current evidence of any condition, therapy, or laboratory abnormality that
    might confound the results of the trial, interfere with the subjects participation
    for the full duration of the trial, or is not in the best interest of the subject to
    participate, in the opinion of the treating investigator.

    - Psychiatric or substance abuse disorders that would interfere with cooperation with
    the requirements of the trial.

    - Pregnant or breastfeeding, or expecting to conceive or father children within the
    projected duration of the trial, starting with the pre-screening or screening visit
    through 120 days after the last dose of trial treatment.

    - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. -
    Active HIV, Hep B virus, and Hep C Virus - Received a live vaccine within 30 days of
    planned start of study therapy.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Number of adverse events

    Secondary Outcome Measures

    Trial Keywords