Post-transplant lymphoproliferative disorder MedDRA version: 20.0 Level: PT Classification code 10051358 Term: Post transplant lymphoproliferative disorder System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Imbruvica
Product Name: Imbruvica
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ibrutinib
CAS Number: 936563-96-1
Other descriptive name: 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Untreated CD-20 positive PTLD with or without EBV association, confirmed after biopsy or resection of tumour (upfront reduction of immunosuppression with or without antiviral therapy is permissible) • Measurable disease of >2.0 cm in diameter and/or bone marrow involvement • Patients having undergone heart, lung, liver, kidney, pancreas, small intestine transplantation, or a combination of the above organ transplantations, or PTLD arising in patients > 6 months post allogeneic stem cell transplantation. PTLD with meningeal or CNS involvement can be included. • Platelet count =100 x 109/L or = 50 x 109/L if bone marrow involvement independent of transfusion support in either situation • Absolute neutrophil count (ANC) =1 x 109/L, independent of growth factor support (GCSF) • Adequate renal and hepatic function defined as the following: • Calculated creatinine clearance = 30 mL/min • AST or ALT= 3.0 times the upper limit of normal (ULN) of the institution's normal range • Bilirubin = 1.5 × ULN. Patients with known Gilbert's syndrome may have a bilirubin level > 1.5 × ULN* • Prothrombin time (PT) (or international normalised ratio (INR)) and partial thromboplastin time (PTT) not to exceed 1.2 times the ULN* (*patients with abnormal bilirubin/PT/INR/PTT due to PTLD may be included in the study) • Left ventricular ejection fraction (LVEF) > 50% or report stating left ventricular function is satisfactory or normal • ECOG performance score = 2 (see Appendix 1) • Age at least 16 years • Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for 12 months after treatment discontinuation. For males, these restrictions apply for 12 months after the last dose of study drug. • Able to give written informed consent Are the trial subjects under 18? yes Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 55 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: • Relapsed or refractory PTLD • Complete surgical extirpation of the tumour or irradiation of residual tumour masses • Treatment with rituximab, chemotherapy or antibody therapy for PTLD • PTLD arising within 6 months of allogeneic stem cell transplantation • Severe organ dysfunction not related to PTLD • T-cell PTLD • Patients requiring concomitant use of strong CYP3A4/5 inhibitors/inducers, including preparations containing St. John’s Wort, or who have received anticoagulation treatment with warfarin or vitamin K antagonists within one week of registration • Known to be HIV-positive • Active hepatitis B or other severe, active infection which would preclude the patient from trial therapy in the clinical judgement of the treating Investigator • Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [?-hCG]) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study. • Life expectancy less than 6 weeks • Any contraindication to the IMPs according to the Summary of Product Characteristics (SmPC)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate complete remission after seven weeks of therapy (evaluated by interim CT scan).;Secondary Objective: To evaluate event-free survival (EFS), response, overall survival (OS), progression-free survival (PFS), treatment-related mortality, tolerability, dose interruptions, discontinuations or reductions, grade III and IV leucocytopenia and grade III and IV infections by treatment group, entry into low risk arm after IR therapy;Primary end point(s): The primary outcome measure is complete remission assessed after seven weeks of therapy and evaluated by interim CT scan.;Timepoint(s) of evaluation of this end point: Patients will be reviewed after seven weeks of therapy. Stage 1 will recruit 24 eligible patients. If at least 7 complete responses on interim CT scan (Day 42-47) are observed then a further 14 patients will be recruited into stage 2. As part of the Simon 2-stage design an early stopping rule is integrated in the design of the study. The single arm trial will need 7/24 successes at the interim stage to proceed to the second stage. The TSC will review safety and futility on at least a 6 monthly basis. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints are response, event-free survival, overall survival, progression-free survival, treatment-related mortality, frequency of grade III and IV leucocytopenia and grade III and IV infections and patients entering into low and high risk arms after IR therapy. ;Timepoint(s) of evaluation of this end point: These endpoints will be evaluated once these timepoints are reached. Survival will be assessed and at a minimum of 2 years post registration. | — |
Countries
United Kingdom
Contacts
Public ContactLouise Dudley
University of Birmingham
Outcome results
None listed