An early phase study using a response based combination therapy of rituxumab and ibrutinib in patients with post-transplant lymphoproliferative disorder (PTLD)

Phase 1

• Conditions: Post-transplant lymphoproliferative disorder; MedDRA version: 20.0Level: PTClassification code 10051358Term: Post transplant lymphoproliferative disorderSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-005454-35-GB
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-08-19
• Last Update Posted: 6 November 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 60

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

• 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)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified