Chemotherapy with methotrexate and cytarabine with or without thiotepa, and with or without rituximab, followed by brain irradiation vs chemotherapy supported by autologous stem cells transplantation for immunocompetent patients with central nervous system lymphoma
| ISRCTN | ISRCTN49014661 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN49014661 |
| ClinicalTrials.gov (NCT) | NCT01011920 |
| Clinical Trials Information System (CTIS) | 2009-012432-32 |
| Protocol serial number | 10139 |
| Sponsor | Southampton University Hospitals NHS Trust |
| Funder | Cancer Research UK Clinical Trials Advisory and Awards Committee |
- Submission date
- 10/08/2011
- Registration date
- 10/08/2011
- Last edited
- 25/10/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Ms Debbie Hamid
Scientific
Scientific
Clinical Trials Unit
MP 131
Tremona Road
Southampton
SO16 6YD
United Kingdom
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomised, interventional |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Randomized phase II trial on primary chemotherapy with high-dose methotrexate and high-dose cytarabine with or without thiotepa, and with or without rituximab, followed by brain irradiation vs high-dose chemotherapy supported by autologous stem cells transplantation for immunocompetent patients with newly diagnosed primary CNS lymphoma. |
| Study acronym | IELSG32 |
| Study objectives | Objectives: To establish in a prospective, randomized phase II trial, the activity of three different chemotherapy combinations in patients with newly diagnosed primary central nervous system lymphoma (PCNSL): 1. High-dose methotrexate (HD-MTX) + high-dose cytarabine (HD-araC) 2. HD-MTX + HD-araC + rituximab 3. HD-MTX + HD-araC + rituximab + thiotepa To establish the efficacy of two consolidation strategies: conventional whole-brain radiotherapy (WBRT) vs. highdose chemotherapy supported by autologous stem cell transplantation (HDC + ASCT) in patients with newly diagnosed PCNSL. |
| Ethics approval(s) | 29/06/2011, ref: 11/LO/0420 |
| Health condition(s) or problem(s) studied | Lymphoma (non-Hodgkin's) |
| Intervention | Patients will be randomised to one of 3 chemotherapy regimens: Arm A Methotrexate & Cytarabine Arm B - Methotrexate & Cytarabine with Rituximab Arm C Methotrexate & Cytarabine with Rituximab and Thiotepa Those who are in SD or respond to treatment will be further randomised to consolidation therapy. Arm D Whole Brain Radiotherapy Arm E BCNU, Thiotepa and Stem Cell Transplant Follow Up Length: 120 month(s); Study Entry : Multiple Randomisations |
| Intervention type | Drug |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | 1. Carmustine 2. Cytarabine 3. Methotrexate 4. Rituximab 5. Thiotepa |
| Primary outcome measure(s) |
Complete remission following primary chemotherapy |
| Key secondary outcome measure(s) |
Failure-free survival at 2 years |
| Completion date | 30/09/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 65 Years |
| Sex | All |
| Target sample size at registration | 126 |
| Total final enrolment | 227 |
| Key inclusion criteria | 1. Histological or cytological assessed diagnosis of non-Hodgkin's lymphoma 2. Diagnostic sample obtained by stereotactic or surgical biopsy, cerebrospinal fluid (CSF) cytology examination or vitrectomy 3. Disease exclusively localized into the central nervous system, CSF, cranial nerves or eyes 4. At least one measurable lesion 5. Previously untreated patients (previous or ongoing steroid therapy admitted) 6. Aged 18-65 years (with ECOG Performance Status 0-3), Aged 66-70 (with ECOG Performance Status 0-2) 7. Adequate bone marrow (PLT = 100000 mm3, Hb = 9 g/dl, ANC = 2.000 mm3) 8. Adequate bone marrow (PLT ≥100000 mm3, Hb ≥ 9 g/dl, ANC ≥ 2.000 mm3), renal (creatinine clearance ≥ 60 ml/min) cardiac (VEF ≥ 50%), hepatic function (total serum bilirubin ≤ 3 mg/dL, AST/ALT and үGT ≤ 2 per upper normal limit value). 9. Sexually active patients of childbearing potential agreeing in implementing adequate contraceptive measures during study participation. (13 is part of 12 inclusion criteria) 10. Absence of any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule 11. Patient-signed informed consent obtained before registration 12. Male or female participants |
| Key exclusion criteria | 1. Patients with lymphomatous lesions outside the CNS 2. Patients with a previous non-Hodgkin lymphoma at any time 3. Previous or concurrent malignancies with the exception of surgically cured carcinoma in-situ of the cervix, carcinoma of the skin or other cancers without evidence of disease at least from 5 years 4. Hepatitis-B-Virus surface antigen (HBsAg) and Hepatitis-C-Virus (HCV) positivity 5. HIV infection, previous organ transplantation or other clinically evident form of immunodeficiency 6.Concurrent treatment with other experimental drugs 7. Concurrent pregnancy or lactation 8. Patients not agreeing to take adequate contraceptive measures during the study 9. Symptomatic coronary artery disease, cardiac arrhythmias uncontrolled with medication or myocardial infarction within the last 6 months (New York Heart Association Class III or IV heart disease) |
| Date of first enrolment | 01/10/2011 |
| Date of final enrolment | 30/09/2013 |
Locations
Countries of recruitment
- United Kingdom
- England
- Germany
- Italy
- Switzerland
Study participating centre
Clinical Trials Unit
Southampton
SO16 6YD
United Kingdom
SO16 6YD
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | 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? |
|---|---|---|---|---|---|
| Results article | results | 01/05/2016 | 10/04/2019 | Yes | No |
| Results article | results | 01/11/2017 | 10/04/2019 | Yes | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Plain English results | 25/10/2022 | No | Yes | ||
| Study website | Study website | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
25/10/2022: Cancer Research UK plain English results link and total final enrolment added.
10/04/2019: Publication reference added.
15/03/2017: No publications found in PubMed, verifying study status with principal investigator
