DPX-Survivac and Checkpoint Inhibitor in DLBCL
SPiReL
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)
1 other identifier
interventional
25
1 country
6
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Mar 2018
Longer than P75 for phase_2
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 14, 2017
CompletedFirst Posted
Study publicly available on registry
November 21, 2017
CompletedStudy Start
First participant enrolled
March 13, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 31, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
July 18, 2023
CompletedResults Posted
Study results publicly available
May 6, 2026
CompletedMay 6, 2026
January 1, 2026
3.6 years
November 14, 2017
February 9, 2026
April 15, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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
Objective Response Rate is the combined Complete Response (CR) and Partial Response (PR) rates using Cheson Criteria (2007) for evaluation. Site Qualified Investigators use radiological reports to calculate the decrease in tumour size from baseline at protocol specified time points.
1 Year
Secondary Outcomes (4)
Duration of Response Using Modified Cheson Criteria.
2 Years
Time to Next Treatment
42 months
Evidence of Regression Using Waterfall Analyses
1 year
Toxicity Profile
1 year
Other Outcomes (4)
Changes in Circulating T Cell Immune Responses to Survivin and Relationship to Peripheral B Cell Numbers
1 year
Changes in T Cell and T Cell Subset Infiltration and Gene Expression Pathways in Treatment Compared to Pre-treatment Tumour Biopsies
1 year
Assess Potential Biomarkers of Immune and Clinical Response From Subject Clinical, Biological and Immunologic Data From Pre-treatment and On-treatment Tumour Biopsies
1 year
- +1 more other outcomes
Study Arms (1)
Single Arm-Investigational
EXPERIMENTALDPX-Survivac Priming dose of 0.5ml. DPX-Survivac Booster dose of 0.1ml. Pembrolizumab 200mg Intravenously. Cyclophosphamide 50mg Twice daily orally.
Interventions
DPX-Survivac Priming dose of 0.5ml on Study days 7 and 28. DPX-Survivac Booster dose of 0.1ml on Study days 84, 140, 196, 252, 308, and 364.
Pembrolizumab 200mg administered intravenously every 3 weeks, commencing on study day 7 to a total of 18 infusions
Cyclophosphamide 50mg twice daily by mouth, administered 7 days on / 7 days off, stating at study day 0, until study day 384
Eligibility Criteria
You may qualify if:
- In order to be eligible for participation in this trial, the subject must:
- Be willing and able to provide written informed consent/assent for the trial.
- Male or female 18+ years of age on day of signing informed consent and of any racial or ethnic group
- 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)
- 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 or,
- 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 or,
- D. for subjects with transformed lymphoma, a treatment for indolent lymphoma within the last 2 years
- Have at least one measurable site of disease based on Cheson Criteria using standard CT imaging.
- 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.
- Have a performance status of 0-1 on the ECOG Performance Scale.
- +7 more criteria
You may not qualify if:
- The subject must be excluded from participating in the trial if the subject:
- 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).
- Patients eligible for possible curative therapies such as ASCT.
- LDH greater than 5 times the upper limit of normal.
- 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).
- Has had previous allogeneic stem cell transplant
- Has known active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients.
- 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.
- 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.
- 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.
- 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.
- Progressive CNS lymphoma requiring treatment within 35 days prior to SD0.
- 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.
- Has known history of, or any evidence of active, non-infectious pneumonitis.
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Merck Sharp & Dohme LLCcollaborator
- Sunnybrook Health Sciences Centrelead
- ImmunoVaccine Technologies, Inc. (IMV Inc.)collaborator
Study Sites (6)
Tom Baker Cancer Centre - Alberta Health Services
Calgary, Alberta, Canada
Nova Scotia Health Authority: Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, B3H 2Y9, Canada
London Health Sciences Centre
London, Ontario, N6A 5W9, Canada
Ottawa Hospital Research Institute
Ottawa, Ontario, Canada
Sunnybrook Health Sciences Centre, Odette Cancer Centre
Toronto, Ontario, M4N 3M5, Canada
McGill University Health Centre
Montreal, Quebec, Canada
Related Publications (2)
Amitai I, Roos K, Rashedi I, Jiang Y, Mangoff K, Klein G, Forward N, Stewart D, Laneuville P, Bence-Bruckler I, Mangel J, Tomlinson G, Berinstein NL. PD-L1 expression predicts efficacy in the phase II SPiReL trial with MVP-S, pembrolizumab, and low-dose CPA in R/R DLBCL. Eur J Haematol. 2023 Aug;111(2):191-200. doi: 10.1111/ejh.13982. Epub 2023 May 8.
PMID: 37157906RESULTPandey A, Roos K, Jiang Y, Mangoff K, Klein G, Forward N, Stewart D, Laneuville P, Bence-Bruckler I, Mangel J, Tomlinson G, Berinstein NL. Characteristics of relapsed/refractory diffuse large B-cell lymphoma patients with durable responses to maveropepimut-S, pembrolizumab, and cyclophosphamide: Long-term follow-up from the SPiReL trial. EJHaem. 2024 Dec 12;6(1):e1062. doi: 10.1002/jha2.1062. eCollection 2025 Feb.
PMID: 39866944DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Neil Berinstein
- Organization
- Sunnybrook Health Sciences Centre
Study Officials
- PRINCIPAL INVESTIGATOR
Neil L Berinstein, MD
Sunnybrook Research Institute
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 14, 2017
First Posted
November 21, 2017
Study Start
March 13, 2018
Primary Completion
October 31, 2021
Study Completion
July 18, 2023
Last Updated
May 6, 2026
Results First Posted
May 6, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
- Time Frame
- Up to 5 years after the closure of the trial
For original data, contact SPiReL@sunnybrook.ca. Individual patient data will not be de-identified, however, data can be shared for a period of up to 5 years after trial closure with formal Confidentiality and Data Transfer agreements in place as appropriate. A data dictionary will not be shared, but the study protocol can be found on ClinicalTrials.gov with trial #NCT03349450 and the Statistical Analysis Plan can be made available with publication.