ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12610000908033

Ethics application status

Approved

Date submitted

25/10/2010

Date registered

25/10/2010

Date last updated

13/06/2024

Date data sharing statement initially provided

27/05/2019

Date results provided

27/05/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

Rituximab in Primary Central Nervous system Lymphoma.
A randomized Dutch/Belgian Hemato-Oncology Cooperative Group (HOVON) / Australasian Leukaemia and Lymphoma Group (ALLG) intergroup study

Scientific title

Rituximab in Primary Central Nervous system Lymphoma.
A randomized Dutch/Belgian Hemato-Oncology Cooperative Group (HOVON) / Australasian Leukaemia and Lymphoma Group (ALLG) intergroup study

Secondary ID [1]

Nederlands Trial Register NTR2427

Universal Trial Number (UTN)

Trial acronym

ALLG NHL24

Linked study record

Health condition

Health condition(s) or problem(s) studied:

primary central nervous system (CNS) lymphoma

Condition category

Condition code

Cancer

Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

2 courses (4 weeks each) of R-MBVP (Rituximab 375mg/m2 intravenously (i.v), course 1 days 0,7,14,21, course 2 days 0 and 14; methotrexate 3g/m2 iv days 1,15 for all courses; Teniposide 100mg/m2 i.v days 2,3 for all courses; BCNU (Carmustine) 100mg/m2 i.v day 4 for all courses; prednisolone 60mg/m2 orally or i.v days 1-5 for all courses)
Following randomisation to MBVP or R-MBVP, patients will undergo an MRI. Patients with less than a complete response (CR) or partial response (PR) will be removed from study. Responding patients undergo consolidation with cytarabine (2 g/m2 i.v days 1,2) and have another MRI. Patients greater than or equal to 61 years of age will finish protocol treatment here. Patients with relapse or progressive disease will be withdrawn from study. Patients less than or equal to 60 years of age will undergo whole brain radiotherapy- if CR or (complete remission-unconfirmed) CRu- 20 x 1.5 Gy; if PR 20 x 1.5 Gy and boost 20 x 0.5 Gy. Patients will then have another MRI.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

2 courses (4 weeks each) of MBVP (methotrexate 3g/m2 iv days 1,15 for all courses; Teniposide 100mg/m2 i.v days 2,3 for all courses; BCNU (Carmustine) 100mg/m2 i.v day 4 for all courses; prednisolone 60mg/m2 orally or i.v days 1-5 for all courses)
Following randomisation to MBVP or R-MBVP, patients will undergo an MRI. Patients with less than a complete response (CR) or partial response (PR) will be removed from study. Responding patients undergo consolidation with cytarabine (2 g/m2 i.v days 1,2) and have another MRI. Patients greater than or equal to 61 years of age will finish protocol treatment here. Patients with relapse or progressive disease will be withdrawn from study. Patients less than or equal to 60 years of age will undergo whole brain radiotherapy- if CR or CRu- 20 x 1.5 Gy; if PR 20 x 1.5 Gy and boost 20 x 0.5 Gy. Patients will then have another MRI.

Control group

Active

Outcomes

Primary outcome [1]

Event-free survival of all patients defined as failure (relapse, no CR or CRu) or death from any cause.

Timepoint [1]

at 1, 3 and 5 years

Secondary outcome [1]

Response rates by MRI

Timepoint [1]

after (R-)MBVP, after high dose cytarabine and after completion of radiotherapy

Eligibility

Key inclusion criteria

1. Patients with a histologically confirmed diagnosis of CD20 positive diffuse large B cell lymphoma (DLBCL) based upon a representative histology specimen of brain biopsy according to the world health organisation (WHO) classification;
OR
2. Patients with a diagnosis of PCNSL based on magnetic resonance imaging (MRI) evidence of brain parenchymal lesion showing homogeneous contrast enhancement suspect for lymphoma;
AND
3. Unequivocal morphological and/or immunophenotypical evidence of cerebrospinal fluid (CSF) CD20 + large cell lymphoma;
4. AND/OR Unequivocal morphological and/or immunophenotypical evidence of CD20 + large cell lymphoma in vitreous fluid;
OR
5. Patients with unequivocal morphological and/or immunophenotypical evidence of CD20 + large cell lymphoma in vitreous fluid AND CSF but without a brain parenchymal lesion;
6. Age 18-70 years inclusive;
7. Performance status with or without administration of steroids WHO/Eastern cooperative group (ECOG) 0-3;
8. Written informed consent.

Minimum age

18 Years

Maximum age

70 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Evidence of systemic lymphoma;
2. History of intolerance of exogenous protein administration;
3. Severe cardiac dysfunction (NYHA classification III-IV, , or Left Ventricular Ejection Fraction < 45%) Congestive heart failure or symptomatic coronary artery disease or cardiac arythmias not well controlled with medication ;
4. Severe pulmonary dysfunction (vital capacity or diffusion capacity < 50% of predicted value);
5. Significant hepatic dysfunction (bilirubin or transaminase greater or equal to 2.5 x upper normal limit) at Screening;
6. Significant renal dysfunction (serum creatinine greater than or equal to 150 micromol/l or clearance < 60 ml/min) at Screening;
7. Presence of third space fluid, such as pleural effusion or ascites;
8. Prior cranial radiotherapy;
9. Active uncontrolled infection;
10. Human immunodeficiency virus (HIV)-positivity;
11. Epstein barr virus (EBV) positive post-transplant lymphoproliferative disorder;
12. Untreated hepatitis B infection (inclusion is possible if adequate antiviral medication e.g. lamivudine or alternative is started and continued for the duration of the trial);
13. Positive pregnancy test in women of reproductive potential;
14. Lactating women;
15. Unable or unwilling to use adequate contraceptive methods (all men, pre-menopausal women) until 12 months after last chemotherapy treatment;
16. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Patients are enrolled and randomised centrally at HOVON data centre.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

sequential generation of randomisation in order of enrolment

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 3

Type of endpoint/s

Efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Active, not recruiting

Date of first participant enrolment

Anticipated

1/05/2010

Actual

21/12/2010

Date of last participant enrolment

Anticipated

Actual

31/05/2016

Date of last data collection

Anticipated

31/05/2024

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,QLD,SA,TAS,WA,VIC

Recruitment hospital [1]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [2]

Princess Alexandra Hospital - Woolloongabba

Recruitment hospital [3]

Royal Prince Alfred Hospital - Camperdown

Recruitment hospital [4]

Royal Hobart Hospital - Hobart

Recruitment hospital [5]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [6]

Sir Charles Gairdner Hospital - Nedlands

Recruitment hospital [7]

Concord Repatriation Hospital - Concord

Recruitment postcode(s) [1]

3002

Recruitment postcode(s) [2]

5000 - Adelaide

Recruitment postcode(s) [3]

4102 - Woolloongabba

Recruitment postcode(s) [4]

2050 - Camperdown

Recruitment postcode(s) [5]

7000 - Hobart

Recruitment postcode(s) [6]

3050 - Parkville

Recruitment postcode(s) [7]

6009 - Nedlands

Recruitment postcode(s) [8]

2139 - Concord

Recruitment outside Australia

Country [1]

Netherlands

State/province [1]

Country [2]

Belgium

State/province [2]

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Roche Products Pty Ltd

Address [1]

4-10 Inman Road
Dee Why NSW 2099
Australia

Country [1]

Australia

Primary sponsor type

Other Collaborative groups

Name

HOVON

Address

VU University Medical Center,
P.O.Box 7057
1007 MB Amsterdam

Country

Netherlands

Secondary sponsor category [1]

Other Collaborative groups

Name [1]

Australasian Leukaemia and Lymphoma Group

Address [1]

Level 2/10 St Andrews Place
East Melbourne, VIC, 3002

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Austin Health

Ethics committee address [1]

Austin Hospital, 145 Studley Road, Heidelberg, VIC 3084

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

23/09/2010

Approval date [1]

01/05/2010

Ethics approval number [1]

Summary

Brief summary

Newly diagnosed PCNS lymphoma patients will be randomised to either 2 courses of MBVP or 2 courses of MBVP+Rituximab. All patients will undergo an MRI at the end of chemotherapy and be assessed for consolidation treatment with AraC, after which these patients will undergo another MRI to determine their eligibility or need for WBRT or not. The primary objective of the trial is event free survival.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Samar Issa

Address

North Middlemore Hospital, Auckland, New Zealand

Country

New Zealand

Phone

+64 9 276 0044

Fax

[email protected]

Contact person for public queries

Name

Delaine Smith

Address

Australasian Leukaemia and Lymphoma Group 35 Elizabeth Street Richmond VIC 3121

Country

Australia

Phone

+61 383739701

Fax

[email protected]

Contact person for scientific queries

Name

Dr Samar Issa

Address

Middlemore Hospital
Private Bag 93311
Auckland

Country

New Zealand

Phone

+ 64 9 276 0044

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

De-identified IPD data for all data collected during the trial

When will data be available (start and end dates)?

Data available 3 months following publication, for an indefinite period

Available to whom?

Data are potentially available to:
• Researchers from not-for-profit organisations
• Commercial organisations
• Other
Based in:
• Any location
Further information:
All data requests will be considered by the primary sponsor on a case by case basis. Requests must include a methodologically sound proposal. Specific conditions of use may apply and will be specified in a data sharing agreement (or similar) that the requester must agree to before access is granted.

Available for what types of analyses?

Any type of analysis
Proposals will be assessed on a case-by-case basis

How or where can data be obtained?

Access can be requested via the Health Data Australia catalogue (https://researchdata.edu.au/health/). Search for the ACTRN number in the catalogue to find datasets associated with this trial or email enquiries to [email protected]

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
23182	Study protocol			[email protected]	Access can be requested via the Health Data Austra... [More Details]

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Rituximab in patients with primary CNS lymphoma (HOVON 105/ALLG NHL 24): a randomised, open-label, phase 3 intergroup study.	2019	https://dx.doi.org/10.1016/S1470-2045%2818%2930747-2
Dimensions AI	Multi-scale spatial modeling of immune cell distributions enables survival prediction in primary central nervous system lymphoma	2023	https://doi.org/10.1016/j.isci.2023.107331

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically