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
EudraCT/CTIS number	2009-012432-32
ClinicalTrials.gov number	NCT01011920
Secondary identifying numbers	10139

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

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-high-dose-chemotherapy-radiotherapy-stem-cell-transplant-people-recently-diagnosed-primary-lymphoma-brain-spinal-cord-ielgs-32

Study website

Contact information

Ms Debbie Hamid
Scientific

Clinical Trials Unit
MP 131
Tremona Road
Southampton
SO16 6YD
United Kingdom

Study information

Study design	Randomised, interventional
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	GP practice
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	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
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	1. Carmustine 2. Cytarabine 3. Methotrexate 4. Rituximab 5. Thiotepa
Primary outcome measure	Complete remission following primary chemotherapy
Secondary outcome measures	Failure-free survival at 2 years
Overall study start date	01/10/2011
Completion date	30/09/2013

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	65 Years
Sex	Both
Target number of participants	Planned Sample Size: 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

England
Germany
Italy
Switzerland
United Kingdom

Study participating centre

Clinical Trials Unit

Southampton
SO16 6YD
United Kingdom

Sponsor information

Southampton University Hospitals NHS Trust
Hospital/treatment centre

Tremona Road
Southampton
SO16 6YD
England
United Kingdom

Website	http://www.suht.nhs.uk/
"ROR"	https://ror.org/0485axj58

Funders

Funder type

Charity

Cancer Research UK Clinical Trials Advisory and Awards Committee

No information available

Results and Publications

Intention to publish date
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?
Results article	results	01/05/2016	10/04/2019	Yes	No
Results article	results	01/11/2017	10/04/2019	Yes	No
Plain English results			25/10/2022	No	Yes
HRA research summary			28/06/2023	No	No

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