- 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
- 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.
- 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