B-Cell Lymphoma

• open label phase II study of R-CHOP + pembrolizumab in primary mediastinal B-cell lymphoma
• strong biologic rationale
• potential to spare toxicity from DA-EPOCH-R and radiotherapy
• comprehensive correlative research planned

Inclusion Criteria

• age > 18 years at time of enrolment
• clinicopathologic diagnosis consistent with primary mediastinal B-cell lymphoma (PMBL)
• no previous treatment for lymphoma (exception: prednisolone ≤100mg daily for ≤7 days)
• adequate organ function (see next page)
• ECOG ≤1
• able to undergo PET-CT
• no concurrent uncontrolled medical condition
• life expectancy > 3 months
• negative blood pregnancy test at screening for WCBP. Effective contraception for both male and female subjects if the risk of conception exists.

system	parameter	requirement
haematologic	neutrophils	≥1.5 x 109/L
	haemoglobin	≥90g/L
	PT/INR, aPTT	≤1.5 x ULN*
renal	creatinine	1.5 x ULN or CrCl ≥30ml/min
hepatic	bilirubin	≤1.5 x ULN (direct bilirubin normal if total bilirubin ≥1.5 x ULN
	ALT/AST	≤2.5 x ULN (≤5x ULN if hepatic involvement)
cardiac	LVEF	≥45% (echo or MUGA)

Key Exclusion Criteria

• lymphoma histology other than PMBL
• clinical presentation inconsistent with PMBL
• CNS involvement by lymphoma
• requires CNS prophylaxis
• received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX40, CD137).
• active autoimmune disease that has required systemic treatment in the past 2 years
• exceptions: type 1 diabetes, vitiligo, psoriasis, thyroid disease not requiring immunosuppression
• patients requiring corticosteroids for hormonal replacement at doses ≤10 mg prednisone or equivalent per day are eligible
• administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is acceptable.
• known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma
• history of (non-infectious) pneumonitis/interstitial lung disease requiring steroids
• prior organ transplantation, including allograft
• prior malignancy within 2 years except for locally curable cancers
• contraindication to vincristine (e.g. neuropathy >grade 1)
• major surgery (except diagnostic biopsy) within 4 weeks of enrolment
• pregnancy or lactation

Louise Hay
louise.hay@health.wa.gov.au
08 6383 3207

Prof. Chan Cheah

Australasian Leukaemia and Lymphoma

Phase 2

NHL35

ACTRN12621001529831p