A Study of CXD101 in Combination With Pembrolizumab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma (PLACARD)
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|ClinicalTrials.gov Identifier: NCT03873025|
Recruitment Status : Not yet recruiting
First Posted : March 13, 2019
Last Update Posted : March 13, 2019
|Condition or disease||Intervention/treatment||Phase|
|Diffuse Large B Cell Lymphoma||Combination Product: Pembrolizumab and CXD101||Phase 1 Phase 2|
Trial Subjects (patients) who are deemed eligible for the trial will initially be entered into the safety run-in stage of the trial. Up to 12 patients will be registered into the safety run-in stage, in cohorts of 3 patients at a time.
3 patients will be registered initially and will be administered a single infusion of pembrolizumab (200mg, day 1) in combination with CXD101 (20mg twice daily days 1 to 5). This is dose level 0.
If 0 to 1 dose limiting toxicity (DLT) is observed, 3 more patients will be entered into the trial and treated at dose level 0. If 0 to 1 DLT is observed across all 6 patients, the maximum tolerated dose (MTD) will be declared and the expansion stage of the trial will be opened.
If more than 1 DLT is observed at dose level 0, 3 patients will be recruited and treated at dose level -1. The CXD101 dose will be reduced by 25% (20mg in the morning and 10mg in the evening, days 1 to 5), while the pembrolizumab dose will remain the same (200mg, day 1).
If 0 or 1 DLT is observed, 3 more patients will be recruited and treated at dose level -1. If 0 or 1 DLT is observed across all 6 patients the maximum tolerated dose will be declared and the expansion stage of the trial will be opened.
If more than 1 DLT is observed at dose level -1 the combination will be deemed excessively toxic and no further patients enrolled.
Once the MTD is declared, the cohort will be expanded and a further 33 patients will be treated at this dose level.
Patients will continue to receive pembrolizumab and CXD101 at 3 weekly intervals for a maximum of 2 years or until disease progression or unacceptable toxicity develops. Patients on pembrolizumab will be seen every 3 weeks during trial treatment. Patients who progress will be seen annually for disease status. Patients completing treating or who stop treatment early for reasons other than disease progression will be followed every 3 months for up to one year after the end of treatment, and annually thereafter until end of trial is declared (when the last patient has completed 1 year follow up).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||45 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase Ib/II Trial of Histone Deacetylase Inhibitor CXD101 in Combination With Programmed Cell Death Protein-1 Inhibitor Pembrolizumab for Relapsed or Refractory Diffuse Large B-cell Lymphoma|
|Estimated Study Start Date :||October 2019|
|Estimated Primary Completion Date :||April 2024|
|Estimated Study Completion Date :||April 2025|
Experimental: Pembrolizumab and CXD101
Initial dose ('dose level 0'):-
Single 200mg pembrolizumab IV infusion (day 1) in combination with oral CXD101 20mg twice daily PO (days 1 to 5) given in 21-day cycles for 2 years or until termination of treatment due to disease progression or unacceptable toxicity.
Reduced dose level ('Dose level -1'; if >1 DLT observed at dose level 0):
Single 200mg pembrolizumab IV infusion (day 1) in combination with oral CXD101 given twice daily, 20mg in the morning and 10mg in the evening (days 1 to 5) given in 21-day cycles for 2 years or until termination of treatment due to disease progression or unacceptable toxicity.
Combination Product: Pembrolizumab and CXD101
Pembrolizumab is a humanised monoclonal antibody which targets the programmed cell death 1 (PD-1) receptor. It blocks a protective mechanism on cancer cells, and allow the immune system to destroy these cancer cells. CXD101 is a histone deacetylase (HDAC) inhibitor which kills cancer cells by blocking the vital functions of HDAC enzymes.
- Safety run in: Determine the maximum tolerated dose of CXD101 given in combination with pembrolizumab [ Time Frame: During first cycle of CXD101 + pembrolizumab (each cycle lasts 21 days; assessment will take into account dose limiting toxicities reported at any time during the first 21 days of treatment) ]MTD to be defined as the highest dose level where 0 or 1 Dose limiting toxicity is observed in 6 patients
- Best Objective Response Rate [ Time Frame: From baseline to end of cycle 6 of treatment (approximately 18 weeks; each cycle lasts 21 days) ]Proportion of patients achieving CR or PR during the first 6 cycles of CXD101 in combination with pembrolizumab using the RECIL criteria
- Overall Response Rate at the end of 4 cycles [ Time Frame: From baseline to end of cycle 4 of treatment (approximately 12 weeks; each cycle lasts 21 days) ]Overall Response of the combination of CXD101 and Pembrolizumab
- Response Duration [ Time Frame: From start of treatment to time of disease progression (any time during study participation, minimum 3 years) ]Time from date of first response confirmation to the first date of progressive disease confirmation
- Best Overall Response at any time point [ Time Frame: From baseline to end of treatment (up to 2 years) ]Best Overall Response of CXD101 in combination with Pembrolizumab
- Best response at end of cycle 6 of treatment [ Time Frame: From baseline to end of cycle 6 of treatment (approximately 18 weeks; each cycle lasts 21 days) ]CR, PR, MR, Stable Disease, Progressive Disease rates over 6 weeks of treatment
- Progression Free Survival [ Time Frame: 52 weeks after commencement of CXD101 and Pembrolizumab ]Progression Free Survival at 1 year
- Overall Survival [ Time Frame: 52 weeks after commencement of CXD101 and Pembrolizumab ]Overall survival at 1 year
- Incidence of treatment-emergent adverse events (safety and tolerability) [ Time Frame: From start of CXD101 and Pembrolizumab until 5 months post-treatment ]Adverse events to be reported during and after treatment, coded using CTCAE v5.0
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): NCT03873025
|Contact: PLACARD Trial Coordinator||+44 email@example.com|
|Contact: Lindsey Stevens||+44 firstname.lastname@example.org|
|Principal Investigator:||Graham Collins||Oxford University Hospitals NHS Trust|