| Eligibility |
Inclusion Criteria:
1. Patients with peripheral T-cell lymphoma (including but not limited to PTCL-NOS,
angioimmunoblastic T-cell lymphoma, anaplastic large T-cell lymphoma). Patients with
mycosis fungoides with large cell transformation with measurable disease are eligible.
2. Disease status defined as refractory to or relapsed after = 1 prior treatment lines.
3. Patients irrespective of transplant eligibility status can be enrolled; however
patients can be seen by SCT team in anticipation for SCT.
4. Subjects with ALK+ ALCL should have been treated with, be ineligible for, or have
refused chemotherapy and brentuximab prior to enrollment on the current study.
5. Patients with a measurable disease, defined by a node or mass with the longest
diameter = 1.5cm.
Inclusion Criteria:
In order to be eligible for participation in this trial, the subject must:
1. Be willing and able to provide written informed consent/assent for the trial.
2. Be 18 years of age on day of signing informed consent.
3. Patients with PTCL should have radiographically measurable disease >/= 1.5cm.
4. Be willing to provide tissue from a newly obtained core or excisional biopsy of a
tumor lesion. Newly-obtained is defined as a specimen obtained up to 12 weeks(84 days)
prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples
cannot be provided (e.g. inaccessible or subject safety concern) may submit an
archived specimen.
5. Have a performance status of 0, 1 or 2 on the ECOG Performance Scale.
6. Demonstrate adequate organ function as defined in Table 1, all screening labs should
be performed within 14 days of treatment initiation.
Table 1 Adequate Organ Function Laboratory Values System Laboratory Value
- Hematological
- Absolute neutrophil count (ANC) = 1000 /mcL
- Platelets =100,000 / mcL. If bone marrow is involved, platelets should be at
least 50K and ANC 750 / mcL
- Hemoglobin = 8g/dL without transfusion or EPO dependency (within 7 days of
assessment)
- Renal
- Serum creatinine OR Measured or calculateda creatinine clearance (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
- Hepatic
- 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
- Albumin > 2 mg/dL
- Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT)
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 =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 aCreatinine clearance should be calculated per
institutional standard.
7. Female subject of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study medication. If
the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required.
8. Female subjects of childbearing potential (Section 5.7.2) must be willing to use an
adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the
course of the study through 120 days after the last dose of study medication.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
9. Male subjects of childbearing potential (Section 5.7. .2 must agree to use an adequate
method of contraception as outlined in Section 5.7. .2- Contraception, starting with
the first dose of study therapy through 120 days after the last dose of study therapy.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
10. Relapsed/refractory Cutaneous T cell Lymphomas (CTCL) patients with transformed and
aggressive T Cell with predominant lymph node involvement and those that are
measurable by standard T Cell criterial. These patients require failure of at least
one prior systemic therapy for the transformed lymphoma.
Exclusion Criteria:
The subject must be excluded from participating in the trial if the subject:
1. Is currently 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.
2. Has a diagnosis of immunodeficiency, is receiving systemic steroids above physiologic
dose (>10mg/day prednisone or equivalent) within 5 half lives after the last dose of
steroid of start of therapy or is receiving any other form of immunosuppressive
therapy.
3. Has a known history of active TB (Bacillus Tuberculosis)
4. Hypersensitivity to pembrolizumab or any of its excipients.
5. 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.
6. 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 prior to starting
therapy.
7. Has a known additional malignancy that is progressing or requires active treatment
within the last 3 years Exceptions include basal cell carcinoma of the skin, resected
renal cell cancer or squamous cell carcinoma of the skin that has undergone
potentially curative therapy or in situ cervical cancer.
8. 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. This exception does not include
carcinomatous meningitis which is excluded regardless of clinical stability.
9. Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
10. Has known history of non-infectious pneumonitis that required systemic steroid use, or
has active pneumonitis.
11. Has an active infection requiring systemic therapy.
12. 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.
13. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
14. 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.
15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
17. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
18. Baseline EKG shows QTcF > 470 msec
19. Concomitant use of strong CYP3A4 inhibitors and inducers.
20. 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.
21. Has undergone prior allogenic hematopoietic stem cell transplantation any time.
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