| Eligibility |
Inclusion Criteria:
- Confirmed mycosis fungoides/Sezary syndrome, disease stage IB (defined as patches,
plaque, or papules that involve 10% of the skin surface viscera) or higher.
- Age = 18 years.
- ECOG Performance Score between 0-1
- Receipt of at least one prior systemic therapy for MF/SS.
- Previous systemic anti-cancer therapy must have been discontinued at least 2 weeks
prior to treatment. See section 6.2 Subject Exclusion Criteria for guidelines
regarding adjuvant and maintenance therapy for prior malignancy.
- Topical or systemic steroids (equivalent to = 10 mg/day of prednisone) may be
considered if dose has been constant and discontinuation may lead to rebound flare in
disease, adrenal insufficiency, and/or unnecessary suffering.
- Prior therapy with gemcitabine allowed.
- Refer to Table 1 for laboratory inclusion criteria.
- The participant (or legally acceptable representative if applicable) provides written
informed consent for the trial.
- A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in Appendix C
- A WOCBP who agrees to follow the contraceptive guidance in Appendix C
- A male participant must agree to use a contraception as detailed in Appendix C of this
protocol from screening and through 6 months after the last dose of gemcitabine or 120
days after the last dose of pembrolizumab (whichever is later) and refrain from
donating sperm during this period.
Table 1: Laboratory Parameters for Inclusion Criteria
System : Laboratory Value
Hematological Absolute neutrophil count (ANC): = 1500/µL Platelets: = 100 000/µL
Hemoglobin: = 9.0 g/dL or = 5.6 mmol/L^a
Renal Creatinine OR Measured or calculated^b creatinine clearance (GFR can also be used in
place of creatinine or CrCl): = 1.5 × ULN OR = 30 mL/min for participant with creatinine
levels > 1.5 × institutional ULN
Hepatic Total bilirubin: = 1.5 ×ULN OR direct bilirubin = ULN for participants with total
bilirubin levels >1.5 × ULN AST (SGOT) and ALT (SGPT): = 2.5 × ULN (= 5 × ULN for
participants with liver metastases)
Coagulation International normalized ratio (INR) OR prothrombin time (PT) Activated partial
thromboplastin time (aPTT): = 1.5 × ULN unless participant is receiving anticoagulant
therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST
(SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular
filtration rate; ULN=upper limit of normal.
- a: Criteria must be met without erythropoietin dependency and without packed red blood
cell (pRBC) transfusion within last 2 weeks.
- b: Creatinine clearance (CrCl) should be calculated per institutional standard.
Note: This table includes eligibility-defining laboratory value requirements for treatment;
laboratory value requirements should be adapted according to local regulations and
guidelines for the administration of specific chemotherapies.
Exclusion Criteria:
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to the first
dose of treatment (see Appendix C). If the urine test is positive or cannot be
confirmed as negative, a serum pregnancy test will be required.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
CTLA-4, OX 40, CD137).
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Has an active infection requiring systemic therapy.
- Has a known additional malignancy that is progressing or has required active treatment
within the past year. Participants with basal cell carcinoma of the skin, squamous
cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical
cancer in situ) that have undergone potentially curative therapy are not excluded.
- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
study intervention. A shorter timeframe down to 2 weeks may be acceptable if the
investigator feels that this is in the best interests of the patient.
- Has received prior systemic anti-cancer therapy including investigational agents,
phototherapy or radiotherapy within 4 weeks prior to the first dose of study
intervention excluding topical steroids. A shorter timeframe down to 2 weeks may be
acceptable if the investigator feels that this is in the best interests of the
patient.
- Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (= 2 weeks of radiotherapy) to non-CNS disease.
- Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette- Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
are generally killed virus vaccines and are allowed; however, intranasal influenza
vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
- Has active autoimmune disease that has required systemic treatment in the past year
(i.e. with use of disease modifying agents, corticosteroids (exceeding 10 mg daily of
prednisone equivalent 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.
- Has known active CNS lymphoma. Participants with previously treated CNS lymphoma may
participate provided they are radiologically stable, i.e. without evidence of
progression for at least 4 weeks by repeat imaging (note that the repeat imaging
should be performed during study screening), clinically stable and without requirement
of steroid treatment for at least 14 days prior to first dose of study intervention.
- Has severe hypersensitivity (= Grade 3) to pembrolizumab and/or any of its excipients.
- Adjuvant or maintenance therapy to reduce the risk of recurrence of other malignancy
(other than T-cell lymphoma) is permissible after discussion with the Principal
Investigator.
- Has a known history of Human Immunodeficiency Virus (HIV) infection.
- Has known active Hepatitis B (defined as Hepatitis B DNA detected by PCR) or known
active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
Patients with evidence of prior hepatitis B infection require prophylaxis with
entecavir or equivalent.
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease.
- Has had an allogenic tissue/solid organ transplant.
- Has a known history of active TB (Bacillus Tuberculosis).
- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
- Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 6 months
after the last dose of gemcitabine or 120 days after the last dose of pembrolizumab
(whichever is later). See Appendix C for details regarding contraception.
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