| Eligibility |
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
- Platelets=50,000 / 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:
1. 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/CTL119 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.
2. Patient has received intervening therapy for lymphoma after CTL019/CTL119 infusion.
3. Has active cytokine release syndrome from CTL019/CTL119 infusion.
4. Has a known history of active TB (Bacillus Tuberculosis).
5. Hypersensitivity to pembrolizumab or any of its excipients.
6. 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.
7. 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.
- Note: Subjects with = Grade 2 neuropathy are an exception to this criterion and
may qualify for the study.
- Note: If subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention in the opinion of the
Principal Investigator prior to starting therapy.
8. Has a 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.
9. Has known 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.
10. Has 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.
11. Has known history of, or any evidence of active, non-infectious pneumonitis.
12. Has an active infection requiring systemic therapy.
13. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
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.
14. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
15. Is 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.
16. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
19. Has received a live vaccine within 30 days of planned start of study therapy. Note:
Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
attenuated vaccines, and are not allowed.
20. Has a history of (non-infectious pneumonitis that required steroids or has current
pneumonitis.
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