Eligibility Details:
Entry Criteria
1. Subjects with histologically proven recurrent DLBCL. Subjects may have recurrence
after primary, secondary or tertiary treatment regimens for DLBCL.
2. Subjects with recurrence at least 90 days post aggressive first line combination
chemotherapy (e.g. RCHOP, Hyper-CVAD or other aggressive "curative" combination),
autologous stem cell transplantation (ASCT), or aggressive second line combination
therapy are eligible.
3. Patients with partial response or measureable disease after first line therapy (who
are not candidates for ASCT) or after second or third line therapy without disease
progression may also be eligible. Patients with recurrence any time after
non-aggressive combination or single agent therapy with or without Rituximab (ie. CVP,
CHL or, VP16) for first, second or third line disease are eligible.
Patients may have evidence of transformed lymphoma with past history of indolent lymphoma
provided current biopsy shows DLBCL. Patients with double hit or high grade lymphomas
including Burkitts lymphoma and High Grade B-Cell lymphoma unclassifiable (with features
intermediate between Burkitts and diffuse large B cell lymphoma) are eligible.
Inclusion Criteria
1. Be willing and able to provide written informed consent/assent for the trial.
2. Male or female 18 years of age or older, on day of signing informed consent and of any
racial or ethnic group
3. Have at least one measurable site of disease based on Cheson Criteria using standard
CT imaging.
4. Be willing to provide tissue from a newly obtained (up to 3 month prior to Day 0)
biopsy of a tumour lesion. If this is not available, the patient must be willing to
undergo a core biopsy prior to starting treatment. They must also be willing to
provide an on-treatment biopsy. Note: Pre-Treatment biopsy's that extend 7 days past
the 3 month timeline indicated above may be used.
5. Have a performance status of 0-1 on the ECOG Performance Scale.
6. Demonstrate adequate organ function as defined in Table 2. Adequate organ function
should be confirmed within 48 hours prior to receiving the first dose of study
medication (day 0). Patients with abnormal liver enzymes of up to 5 times the upper
limit of normal and/or reduced GFR of 50-100% normal range can be considered for
enrolment if the alteration is due to lymphoma.
7. Previous localized surgery, radiotherapy, chemotherapy, and immunotherapy more than 21
days prior to SD0. Cyclophosphamide, up to 100 mg/day, may be administered until SD-1
for subjects already receiving as a single agent therapy.
8. Subjects must have evidence of survivin expression in pre-treatment tumour sample (>
10% of tumour cells stained).
9. A life expectancy > 6 months.
10. 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 (day
0). If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required.
11. Female subjects of childbearing potential should be willing to use 2 methods of birth
control or be surgically sterile, or abstain from heterosexual activity for the course
of the study through 120 days after the last dose of study medication (Reference
Section 6.1.8). Subjects of childbearing potential are those who have not been
surgically sterilized or have not been free from menses for > 1 year.
12. Male subjects should agree to use an adequate method of contraception starting with
the first dose of study therapy through to 120 days from the last study visit.
13. Ability to comply with protocol requirements.
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 21 days of the first dose of treatment (SD0).
2. Patients eligible for possible curative therapies such as ASCT.
3. LDH greater than 5 times the upper limit of normal
4. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 35 days prior to the first dose of
trial treatment (SD0), except that used as pre-medication for chemotherapy or
contrast-enhanced studies are eligible. Subjects may be on physiologic doses of
replacement prednisone or equivalent doses of corticosteroid (<10 mg daily).
5. Has had previous allogeneic stem cell transplant
6. Has known active TB (Bacillus Tuberculosis)
7. Hypersensitivity to Pembrolizumab or any of its excipients.
8. Has had a prior anti-cancer monoclonal antibody (mAb) within 21 days prior to study
Day 0 or who has not recovered (i.e., ≤ Grade 1) from adverse events due to agents
administered more than 21 days earlier.
9. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 21 days prior to study Day 0. Subjects must have recovered from all acute
toxicities from prior treatments; peripheral neuropathy must be ≤ grade 2.
10. 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.
11. 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 35 days prior to trial treatment.
12. Progressive CNS lymphoma requiring treatment within 35 days prior to SD0.
13. Has history of 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 (eg., thyroxine, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
not considered a form of systemic treatment.
14. Has known history of, or any evidence of active, non-infectious pneumonitis.
15. Thyroiditis within the past 5 years.
16. Has an active infection requiring systemic therapy. Note: Subjects completing a course
of antibiotic for acute infection 7 days prior to SD0 and who do not experience a
recurrence of symptoms or fever are eligible.
17. 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.
18. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
19. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with screening visit to 120 days post
completion of study
20. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
21. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
22. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected). Evidence of Hepatitis B surface antigen without
transaminitis is allowed provided patient is treated with anti-viral therapy (Heptavir
or Tenofovir)
23. Patients who have received prior survivin based vaccines.
24. Acute or chronic skin disorders that will interfere with subcutaneous injection or
subsequent assessment of potential skin reactions.
25. Serious intercurrent chronic or acute illness, such as cardiac disease (New York Heart
Association class III or IV), hepatic disease, or other illness considered by the
investigator as an unwarranted high risk for an investigational product.
26. Allergies to any vaccine, that after discussion with the medical monitor are serious
enough to warrant exclusion from this study.
27. 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 are live attenuated vaccines, and
are not allowed
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-yes
