Investigating the most appropriate dose and effectiveness of thiotepa in combination with ifosphamide, etoposide and rituximab in patients with lymphoma arising in the brain or spinal cord
| ISRCTN | ISRCTN12857473 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12857473 |
| EudraCT/CTIS number | 2014-000227-24 |
| Secondary identifying numbers | 17668 |
- Submission date
- 03/12/2014
- Registration date
- 03/12/2014
- Last edited
- 15/02/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English Summary
Contact information
Scientific
Cancer Research UK Clinical Trials Unit
School of Cancer Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
Study information
| Study design | Non-randomised, interventional |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | A study of thiotepa, ifosphamide, etoposide and rituximab for the treatment of relapsed or refractory primary central nervous system lymphoma |
| Study acronym | TIER |
| Study hypothesis | The phase I dose finding component is a 3+3 cohort design which will recruit up to 18 patients in order to find the MTD of thiotepa in combination with ifosphamide, etoposide and rituximab (TIER). All patients recruited into phase I at the MTD will also contribute towards phase II. The phase II study is based on an A'Hern’s design to assess the activity of thiotepa in combination with ifosphamide, etoposide and rituximab (TIER). 28 patients will be recruited in total in phase II (including some patients from phase I). |
| Ethics approval(s) | 14/LO/1568; First MREC approval date |
| Condition | Primary central nervous system lymphoma |
| Intervention | Etoposide, 250mg/m2 day 2 of 21 day cycle; Ifosphamide, 2g/m2/day days 2-4 for each 21 day cycle.; Rituximab, 375mg/m2/day days 1-2 for each 21 day cycle; Thiotepa, Chemotherapy (doses 20mg/m2 - 50mg/m2) |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I/II |
| Drug / device / biological / vaccine name(s) | 1. Etoposide 2. Ifosphamide 3. Rituximab 4. Thiotepa |
| Primary outcome measure | MTD of thiotepa in combination with ifosphamide, etoposide and rituximab (TIER) Timepoint(s): End of 2 cycles of treatment |
| Secondary outcome measures | 1. 2 year event free survival (EFS); Timepoint(s): 2 years after trial treatment 2. 2 year overall survival (OS); Timepoint(s): 2 years after trial treatment 3. 2 year progression free survival (PFS); Timepoint(s): 2 years after trial treatment 4. CR rate after 2 cycles of TIER; Timepoint(s): End of 2 cycles of treatment 5. Overall response rate (Complete Response (CR) + Complete Response: unconfirmed (CRu) + Partial Res; Timepoint(s): end of 2 cycles of treatment 6. Proportion of patients proceeding to high-dose therapy and autologous stem cell transplant (HDT-AS; Timepoint(s): Following trial treatment 7. Rate of successful stem cell harvest; Timepoint(s): After completing trial treatment 8. Toxicity of TIER using the National Cancer Institute Common Terminology Criteria for Adverse Event; Timepoint(s): All cycles of trial treatment |
| Overall study start date | 12/12/2014 |
| Overall study end date | 31/10/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Planned Sample Size: 40; UK Sample Size: 40 |
| Total final enrolment | 36 |
| Participant inclusion criteria | 1 Age ≥ 16 years of age 2. Histologically confirmed* CD20+ Diffuse Large B Cell Lymphoma (DLBCL) confined to the central nervous system 3. Relapsed or refractory primary central nervous system lymphoma (PCNSL) according to the following definition : 3.1. One or two prior chemotherapy regimen(s), of which at least one regimen contained highdose methotrexate at a dose of >1g/m2. 3.2. Minimum of one cycle containing highdose methotrexate 4. ECOG performance status 0,1 or 2 (or 3 if attributed to lymphoma) 5. Adequate organ function: 5.1. Bone marrow: platelets >80 x109/L, neutrophils >1 x109/L, haemoglobin >80 g/L 5.2. Hepatic: bilirubin <1.5 x upper limit of normal (ULN) (unless isolated unconjugated hyperbilirubinaemia attributable to Gilbert’s syndrome) 5.3. Renal: eGFR ≥40ml/min (Cockcroft-Gault) 5.4. Cardiorespiratory (as judged by the Local Investigator): clinically relevant cardiac or pulmonary function tests must be performed if there is a previous history of significant cardiac or pulmonary impairment 6. Able to comply with the scanning requirements of the study 7. Valid Informed consent |
| Participant exclusion criteria | 1. Systemic involvement with lymphoma 2. Active infection requiring intravenous antimicrobials 3. Chemotherapy for lymphoma within 4 weeks registration 4. Wholebrain radiotherapy within 6 months of registration 5. Relapse within 1 year of a Thiotepabased autologous stem cell transplant 6. Prior therapy with the RIE (Rituximab – ifosphamide and etoposide) regimen 7. Evidence of HIV or Hepatitis C infection 8. Hepatitis B infection* 9. Serum albumin <25g/l 10. Pregnant and lactating patients (patients of childbearing potential must have a negative pregnancy test prior to study entry) 11. Competent pPatients and competent patients with partners of childbearing potential not willing to use effective contraception during and for 12 months after therapy |
| Recruitment start date | 12/12/2014 |
| Recruitment end date | 30/04/2019 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
Study participating centres
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
Birmingham
B15 2TH
United Kingdom
AB25 2ZN
United Kingdom
G12 0YN
United Kingdom
SE5 9RS
United Kingdom
LS9 7TF
United Kingdom
L9 7AL
United Kingdom
M20 4BX
United Kingdom
NE7 7DN
United Kingdom
NG5 1PB
United Kingdom
OX3 7LE
United Kingdom
PL6 8DH
United Kingdom
NW1 2BU
United Kingdom
SM2 5PT
United Kingdom
S10 2JF
United Kingdom
SO16 6YD
United Kingdom
WV10 0QP
United Kingdom
Sponsor information
University/education
Cancer Research UK Clinical Trials Unit, Institute for Cancer Studies, Edgbaston
Birmingham
B15 2TT
England
United Kingdom
"ROR" |
https://ror.org/03angcq70 |
|---|
Funders
Funder type
Government
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/10/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Plain English results | 25/10/2022 | No | Yes | ||
| Basic results | 15/02/2023 | 15/02/2023 | No | No | |
| Results article | 26/10/2021 | 15/02/2023 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Additional files
Editorial Notes
15/02/2023: The following changes have been made:
1. An updated basic results summary has been uploaded.
2. Publication reference added.
14/02/2023: The basic results summary has been removed, pending addition of an updated version.
25/10/2022: Plain English results added.
03/05/2022: The basic results have been uploaded as an additional file.
20/09/2021: Internal review.
12/12/2019: The EudraCT number was added.
17/05/2019: The following changes were made to the trial record:
1. The overall end date was changed from 30/06/2021 to 31/10/2021.
2. The intention to publish date was changed from 30/06/2022 to 31/10/2022.
3. The total final enrolment was added.
03/04/2019: The condition has been changed from "Topic: Cancer; Subtopic: Lymphoma; Disease: Lymphoma (non-Hodgkin's)" to "Primary central nervous system lymphoma" following a request from the NIHR.
27/02/2019: Internal review.
15/01/2019: The intention to publish date, 30/06/2022, has been added.
14/01/2019: The recruitment end date was changed from 31/12/2018 to 30/04/2019.
16/04/2018: The following changes were made:
1. Recruitment end date was changed from 17/11/2017 to 31/12/2018
2. Overall trial end date was changed from 17/11/2017 to 30/06/2021
3. Scientific title was changed from 'A Phase I/II study of thiotepa, ifosphamide, etoposide and rituximab for the treatment of relapsed or refractory primary central nervous system lymphoma' to 'A study of thiotepa, ifosphamide, etoposide and rituximab for the treatment of relapsed or refractory primary central nervous system lymphoma'
4. 16 trial participating centres were added.
5. Louise Hopkins replaced Kathryn Paterson as primary contact.
