DPX-Survivac and Checkpoint Inhibitor in DLBCL (SPiReL)
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|ClinicalTrials.gov Identifier: NCT03349450|
Recruitment Status : Active, not recruiting
First Posted : November 21, 2017
Last Update Posted : February 16, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Adult Diffuse Large Cell Lymphoma Recurrent Adult Refractory Diffuse Large B-Cell Lymphoma||Biological: DPX-Survivac Biological: Pembrolizumab Drug: Cyclophosphamide 50mg||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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)|
|Actual Study Start Date :||March 13, 2018|
|Estimated Primary Completion Date :||April 2021|
|Estimated Study Completion Date :||April 2022|
Experimental: Single Arm-Investigational
DPX-Survivac Priming dose of 0.5ml. DPX-Survivac Booster dose of 0.1ml.
Pembrolizumab 200mg Intravenously.
Cyclophosphamide 50mg Twice daily orally.
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
Drug: Cyclophosphamide 50mg
Cyclophosphamide 50mg twice daily by mouth, administered 7 days on / 7 days off, stating at study day 0, until study day 384
- 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 ]
- To document changes in tumour volume using waterfall analyses [ Time Frame: 1 Year ]Tumor volume measurements will be obtained at multiple time points by adding the volumes of the perpendicular measurements for up to 6 target lesions
- To document the toxicity profile [ Time Frame: 1 Year ]Number of participants with abnormal laboratory values and/or adverse events related to treatment will be assessed.
- To document duration of response using modified Cheson criteria. [ Time Frame: 2 Years ]
- To document time to next treatment [ Time Frame: 2 Years ]
- Exploratory Outcome 1 [ Time Frame: 1 year ](1) To document the changes in circulating T cell immune responses to survivin and relationship to peripheral B cell numbers
- Exploratory Outcome 2 [ Time Frame: 1 year ]To document changes in T cell and T cell subset infiltration and gene expression pathways in treatment compared to pre-treatment tumour biopsies
- Exploratory Outcome 3 [ Time Frame: 1 year ]To assess potential biomarkers of immune and clinical response from pre-treatment and on-treatment tumor biopsies
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03349450
|Tom Baker Cancer Centre - Alberta Health Services|
|Calgary, Alberta, Canada|
|Canada, Nova Scotia|
|Nova Scotia Health Authority: Queen Elizabeth II Health Sciences Centre|
|Halifax, Nova Scotia, Canada, B3H 2Y9|
|London Health Sciences Centre|
|London, Ontario, Canada, N6A 5W9|
|Ottawa Hospital Research Institute|
|Ottawa, Ontario, Canada|
|Sunnybrook Health Sciences Centre, Odette Cancer Centre|
|Toronto, Ontario, Canada, M4N 3M5|
|McGill University Health Centre|
|Montréal, Quebec, Canada|
|Principal Investigator:||Neil L Berinstein, MD||Sunnybrook Research Institute|