Relapsed or refractory primary central neurvous system lymphoma. MedDRA version: 20.0 Level: PT Classification code 10007953 Term: Central nervous system lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Tepadina
Product Name: Tepadina
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Thiotepa
CAS Number: 52-24-4
Concentration unit: mg milligram(s)
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age = 16 years of age • Histologically confirmed* CD20+ Diffuse Large B-Cell Lymphoma (DLBCL) confined to the central nervous system • Relapsed or refractory primary central nervous system lymphoma (PCNSL) according to the following definition : o one or two prior chemotherapy regimen(s), of which at least one regimen contained high-dose methotrexate at a dose of >1g/m2. • ECOG performance status 0,1 or 2 (or 3 if attributed to lymphoma) • Adequate organ function o Bone marrow: platelets >80 x109/L, neutrophils >1 x109/L, haemoglobin >80 g/L o Hepatic: bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 14
Exclusion criteria
Exclusion criteria: • Evidence of Systemic lymphoma • Active infection requiring intravenous antimicrobials • Chemotherapy for lymphoma within 4 weeks registration • Whole-brain radiotherapy within 6 months of registration • Relapse within 1 year of a Thiotepa-based autologous stem cell transplant • Prior therapy with the R-IE (Rituximab – ifosphamide and etoposide) regimen with the last year • Evidence of HIV or Hepatitis C infection • Hepatitis B infection* • Serum albumin <25g/l • Pregnant and lactating patients (patients of childbearing potential must have a negative pregnancy test prior to study entry) • Competent pPatients and competent patients with partners of childbearing potential not willing to use effective contraception during and for 12 months after therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The first phase (Phase 1) of the study is to find the maximum safe dose (maximum Tolerated Dose) of thiotepa which is safe to give in combination with ifosphamide, etoposide and rituximab in patients with Primary Central Nervous System Lymphoma (PCNSL). The second phase (Phase 2) is to look at how effective the combinastion of drugs are in treating (PCNSL). We will assess this by determining the Overall response rate (Complete Response (CR) + Complete Response: unconfirmed (CRu) + Partial Response (PR)) after 2 cycles of TIER treatment, as assessed by the ‘International Workshop to Standardise Baseline Evaluation and Response Criteria for Primary CNS Lymphoma'. ;Secondary Objective: To determine: The Toxicity of the TIER treatment using common terminology criteria for adverse events (CTCAE) version 4 The Complete response rate after 2 cycles of TIER The 2 year progression free survival (PFS) The 2 year event free survival (EFS) The 2 year overall survival (OS) The proportion of patients proceeding to high-dose therapy and autologous stem cell transplant (HDT-ASCT) The rate of successful stem cell harvest for patients proceeding to transplant Exploratory Outcome Measures Analysing the MRI scans to look for MRI-based prognostic and response parameters Analysing the Pathobiological features of relapsed/refractory primary central nervous system lymphoma cases ;Primary end point(s): Phase I Maximum Tolerated Dose (MTD) of thiotepa in combination with ifosphamide, etoposide and rituximab (TIER) Phase II Overall response rate (Complete Response (CR) + Complete Response: unconfirmed (CRu) + Partial Response (PR)) after 2 cycles of TIER treatment, as assessed by the International Workshop to Standardise Baseline Evaluation and Response Criteria for Primary CNS Lymphoma ;Timepoint(s) of evaluation of this end point: The phase I outcome will be measured after the required number of patients have completed 1 cycle of TIER treatment as per the 3+3 des | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Toxicity of TIER using common terminology criteria for adverse events (CTCAE) version 4 • Complete response rate after 2 cycles of TIER • 2 year progression free survival (PFS) • 2 year event free survival (EFS) • 2 year overall survival (OS) • Rate of successful stem cell harvest • Proportion of patients proceeding to high-dose therapy and autologous stem cell transplant (HDT-ASCT) ;Timepoint(s) of evaluation of this end point: Analysis will be predominantly descriptive, with p-values given where appropriate for information only •The number and proportion of patients experiencing toxicity, will be reported with 95% confidence intervals (CIs) •The number of patients achieving complete response as assessed by the International Workshop to Standardise Baseline Evaluation and Response Criteria for PCNSL after 2 cycles of TIER will be reported as a proportion of the total number of patients registered •Time to event outcomes will be assessed using the method of Kaplan and Meier with point estimates presented at 6, 12 and 24 months with 95% CIs and median survival time •The rate of successful stem cell harvest and proportion of patients proceeding to HDT-ASCT will be reported with 95% CIs | — |
Countries
United Kingdom
Contacts
Public ContactLouise Hopkins
Cancer Research UK Clinical Trials Unit
Outcome results
None listed