Clinical Trials /

DPX-Survivac and Checkpoint Inhibitor in DLBCL



This is a Phase 2 non-randomized, open label, uncontrolled, efficacy and safety study. Study participants will receive two priming doses of 0.5mL of DPX-Survivac 21 days apart and up to six 0.1ml maintenance injections every two months with low dose metronomic oral cyclophosphamide (50 mg BID) for one year or until disease progression, whichever occurs first. Pembrolizumab 200 mg will be administered every 3 weeks for up to one year or until disease progression, whichever occurs first.

Related Conditions:
  • Burkitt Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Double-Hit Lymphoma
  • Transformed Non-Hodgkin Lymphoma
Recruiting Status:

Active, not recruiting


Phase 2

Trial Eligibility



  • Brief Title: DPX-Survivac and Checkpoint Inhibitor in DLBCL
  • Official Title: Phase 2 Study of an Immune Therapy, DPX-Survivac With Low Dose Cyclophosphamide Administered With Pembrolizumab in Patients With Persistent or Recurrent/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Clinical Trial IDs

  • ORG STUDY ID: 0891
  • NCT ID: NCT03349450


  • Adult Diffuse Large Cell Lymphoma
  • Recurrent
  • Adult Refractory Diffuse Large B-Cell Lymphoma


DPX-SurvivacSingle Arm-Investigational
PembrolizumabSingle Arm-Investigational
Cyclophosphamide 50mgSingle Arm-Investigational


This is a Phase 2 non-randomized, open label, uncontrolled, efficacy and safety study. Study participants will receive two priming doses of 0.5mL of DPX-Survivac 21 days apart and up to six 0.1ml maintenance injections every two months with low dose metronomic oral cyclophosphamide (50 mg BID) for one year or until disease progression, whichever occurs first. Pembrolizumab 200 mg will be administered every 3 weeks for up to one year or until disease progression, whichever occurs first.

Detailed Description

      This is a Phase 2, non-randomized, open-label, uncontrolled, efficacy and safety trial.

      Participants will receive 2 priming injections (0.5ml) of DPX-Survivac 3 weeks apart on Study
      Days 7 and 28. In addition, up to 6 maintenance injections (0.1ml) over the course of the
      study occurring on Study Days 84, 140, 196, 252, 308, and 364. All injections will be given
      under the skin of the upper thigh.

      Participants will receive metronomic oral cyclophosphamide (50mg BID; 7 days on / 7 days off)
      for study period.

      Pembrolizumab 200mg will be administered intravenously every 3 weeks, commencing on study day
      7, to a total of 18 infusions.

      If a participant is removed from the trial prior to the completion of at least 4 doses of
      Pembrolizumab and 3 injections of DPX-Survivac, that particiapnt may be replaced to determine
      the efficacy of treatment in a minimum of 16 participants.

      DPX-Survivac injection sites will be evaluated throughout the study and if evidence of
      significant reaction, an Injection site reaction biopsy will be sought.

      During the course of the study, blood will be drawn to evaluate immune cells and the effect
      that DPX Survivac will have on the participants immune system. During all treatment cycles a
      physical exam and questions about the participants general health will be performed.

      Participants will undergo "re-staging" to assess the status of their disease at approximately
      study day 70 (if there is evidence of Grade 2 or greater injection site reaction or
      ulceration evident on study day 49) or routinely at approximately study day 91, and again at
      end of study or study withdrawal for all participants.

      A follow-up tumour biopsy will be requested between study day 77-83 for participants with any
      grade 2 or greater Injection site reaction or ulceration on SD49 or between SD98 and SD104 if
      no evidence of injection site reaction or ulceration.

      Upon completion of study, participants will be monitored every 2 months for 1 year.

Trial Arms

Single Arm-InvestigationalExperimentalDPX-Survivac Priming dose of 0.5ml. DPX-Survivac Booster dose of 0.1ml. Pembrolizumab 200mg Intravenously. Cyclophosphamide 50mg Twice daily orally.
  • DPX-Survivac
  • Pembrolizumab
  • Cyclophosphamide 50mg

Eligibility Criteria

        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. Male or female 18+ years of age on day of signing informed consent and of any racial
             or ethnic group

          3. Has:

             A. histologically proven DLBCL with recurrence after first, second or tertiary
             treatment regimens for DLBCL or,

             B. evidence of transformed lymphoma with past history of indolent lymphoma with
             current biopsy showing DLBCL) or,

             C. 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)

          4. Has had:

             A. recurrence requiring therapy 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), CART therapy, or aggressive
             second line combination therapy or,

             B. 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

             C. recurrence any time after non-aggressive combination or single agent therapy with
             or without Rituximab (i.e. CVP, CHL or, VP16) for first, second or third line disease

             D. for subjects with transformed lymphoma, a treatment for indolent lymphoma within
             the last 2 years

          5. Have at least one measurable site of disease based on Cheson Criteria using standard
             CT imaging.

          6. Be willing to provide tissue from a newly obtained (up to 3 months + 7 days prior to
             Study 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.

          7. Have a performance status of 0-1 on the ECOG Performance Scale.

          8. Demonstrate adequate organ function as defined in Table 2, within 48 hours prior to
             receiving the first dose of study medication (SD0). 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.

          9. 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.

         10. A life expectancy > 6 months.

         11. Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 48 hours prior to receiving the first dose of study medication (SD0).
             If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
             test will be required.

         12. 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. Subjects of
             childbearing potential are those who have not been surgically sterilized or have not
             been free from menses for > 1 year.

         13. 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 dose of study

         14. Ability to comply with protocol requirements.

        Exclusion Criteria

        The subject must be excluded from participating in the trial if the subject:

          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 SD0 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 SD0. 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 in situ cervical cancer, basal cell carcinoma of the skin or
             squamous cell carcinoma of the skin that has undergone potentially curative therapy.

         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 (e.g., 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. 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 after last
             dose of study medication.

         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 of the
             DPX-Survivac 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. 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
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To document the objective response rate using modified Cheson criteria to treatment with DPX-Survivac and low dose cyclophosphamide administered together with Pembrolizumab in participants with recurrent, survivin-expressing B cell lymphomas
Time Frame:1 Year
Safety Issue:

Secondary Outcome Measures

Measure:To document changes in tumour volume using waterfall analyses
Time Frame:1 Year
Safety Issue:
Description:Tumor volume measurements will be obtained at multiple time points by adding the volumes of the perpendicular measurements for up to 6 target lesions
Measure:To document the toxicity profile
Time Frame:1 Year
Safety Issue:
Description:Number of participants with abnormal laboratory values and/or adverse events related to treatment will be assessed.
Measure:To document duration of response using modified Cheson criteria.
Time Frame:2 Years
Safety Issue:
Measure:To document time to next treatment
Time Frame:2 Years
Safety Issue:


Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Sunnybrook Health Sciences Centre

Trial Keywords

  • Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma, Large B-Cell, Diffuse
  • Neoplasms by Histologic Type
  • Neoplasms
  • Lymphoproliferative Disorders
  • Lymphatic Diseases
  • Immunoproliferative Disorders
  • Immune System Diseases
  • Lymphoma, Non-Hodgkin
  • Cyclophosphamide
  • Pembrolizumab
  • Immunosuppressive Agents
  • Immunologic Factors
  • Physiological Effects of Drugs
  • Antirheumatic Agents
  • Antineoplastic Agents, Alkylating
  • Alkylating Agents
  • Molecular Mechanisms of Pharmacological Action
  • Antineoplastic Agents
  • Myeloablative Agonists
  • Canada
  • Ontario
  • Diffuse Large B Cell Lymphoma
  • refractory
  • relapsed
  • checkpoint inhibitor
  • vaccine
  • DPX-Survivac
  • Survivin
  • Immunotherapy
  • Transformed Lymphoma
  • Double Hit
  • Large Cell Lymphoma
  • Keytruda

Last Updated

February 16, 2021