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Trial Details
Trial status:
Closed
Recruitment start date:
Funder:
Celleron Therapeutics Limited
Sponsor:
UCL
Chief Investigator:
Dr Graham Collins
Recruitment target:
Up to 45
EudraCT number:
2018-004522-29
Contact details:
ctc.placard@ucl.ac.uk
Lay summary:
PLACARD
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
Description
Design:

Phase Ib/II non randomised multi centre study


Treatment:

3 patients will be recruited and receive pembrolizumab (200mg IV on day 1) in combination with CXD101 (20mg oral twice daily, days 1 to 5) of each treatment cycle (21 days)

If 0 or 1 DLT is observed 3 more patients will be recruited.  If 0 or 1 DLT is observed across all 6 patients, the MTD will be declared and the expansion phase opened.

If more than 1 DLT is observed at any point, 3 patients will be recruited 1 dose level down and will receive pembrolizumab (200mg IV on day 1) in combination with CXD101 (given twice daily orally at 20mg in the morning and 10mg in the evening, days 1 to 5) of each treatment cycle.  If 0 or 1 DLT is observed, 3 more patients will be recruited.  If 0 or 1 DLT is observed across all 6 patients the MTD will be declared and the expansion phase opened.  If more than 1 DLT is observed at any point 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.  The DLT assessment period is the first 21 days of treatment.

Key inclusion/exclusion criteria:

Inclusion

  • Biopsy confirmed DLBCL, relapsed/refractory after 2 or more lines of prior therapy and not suitable for ASCT or relapsed post ASCT
  • Measurable disease (of >15mm in a node or >10mm in extranodal tissue)
  • Age 18 or over
  • ECOG PS 0 or 1 or PS 2 if due to the disease
  • Adequate organ and bone marrow function
  • INR or PT or aPTT: 1.5 or less x ULN unless participant is receiving anticoagulant therapy
  • Adequate renal and liver function

Exclusion

  • Post transplant lymphoproliferative disorder
  • Pregnant or breast feeding
  • Patients with corrected QTc (QTcF or QTcB) interval >450msec
  • Clinically significant cardiac disease
  • Known active CNS involvement by lymphoma
  • Clinically significant active infection requiring antibiotic or antiretroviral therapy
  • Active autoimmune disease that has required systemic treatment in the past 2 years
  • History of (non-infectious) pneumonitis that required steroids or has current pneumonitis
  • History of immune hepatitis or myocarditis
  • Systemic anti-cancer therapy within 4 weeks (12 weeks for CAR T-cells)
  • Prior radiotherapy within 2 weeks
  • Received a live vaccine within 30 days
  • Have taken an IMP/investigational device within 4 weeks
  • Major surgery within 4 weeks
  • Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 or agent directed to another stimulatory or co-inhibitory T-cell receptor
  • Prior allogeneic haematopoietic stem cell transplant or allogeneic CAR T-cell therapy.  Prior autologous CAR T-cell is allowed but must be more than 12 weeks post infusion
  • Diagnosis of prior immunodeficiency, organ-transplant requiring immunosuppressive therapy, known HIV or AIDS related illness
  • Positive serology for hepatitis B or C
  • Severe hypersensitivity to pembrolizumab or CXD101
  • Known psychiatric or substance abuse
  • Non-haematological malignancy within the past 3 years
  • Current or prior use of immunosuppressive therapy within 7 days
  • Unable to swallow tablets

Duration of recruitment: 30 months
Aim
To determine the tolerability and efficacy (with respect to best objective overall response rate during the first 6 cycles, overall survival and progression free survival, of CXD101 in combination with pembrolizumab for patients with relapsed/refractory Diffuse Large B-cell Lymphoma
Trial protocols
Trial protocols must not be applied to patients treated outside trials. UCL CTC can only ensure that approved trial investigators are provided with amendments to protocols.
No protocols have been currently made available for download
Trial documents
No documents have been currently made available for download
Contact Us
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