Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609001077257
Ethics application status
Approved
Date submitted
5/12/2008
Date registered
16/12/2009
Date last updated
4/08/2023
Date data sharing statement initially provided
4/08/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
'A multi-centre phase II trial of early treatment intensification with R-ICE (rituximab – ifosfamide, carboplatin, etoposide) chemotherapy followed by BEAM ( BCNU(BCNU is Carmustine), etoposide, ara-C (ara-C is Cytarabine), melphalan) high dose chemotherapy and autologous stem cell transplantation for patients with poor prognosis diffuse large B-cell lymphoma
Scientific title
This is a multi-centre phase II trial of early treatment intensification with R-ICE (rituximab – ifosfamide, carboplatin, etoposide) chemotherapy followed by BEAM ( BCNU(BCNU is Carmustine), etoposide, ara-C (ara-C is Cytarabine), melphalan) high dose chemotherapy and autologous stem cell transplantation for patients with poor prognosis diffuse large B-cell lymphoma as identified by interim-treatment PET/CT (Positron emission tomography - computed tomography) performed after four cycles of R-CHOP-14 (rituximab and Cyclophosphamide, Doxorubicin, Vincristine, Prednisone - CHOP - every 14 days) chemotherapy.
Universal Trial Number (UTN)
Trial acronym
ALLG NHL21
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Patients with CD20+ diffuse large B cell lymphoma (DLBCL) with low intermediate, high intermediate, or high risk disease or low risk disease with bulky tumour (> 7.5 cm) who are considered fit and eligible for high dose chemotherapy (HDCT) with Z-BEAM ( Zevalin - BEAM ( BCNU(BCNU is Carmustine), etoposide, ara-C (ara-C is Cytarabine), melphalan) and autologous stem cell transplantation (ASCT). 4074 0
Condition category
Condition code
Cancer 4282 4282 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will receive 4 cycles of R-CHOP (rituximab Cyclophosphamide, Doxorubicin, Vincristine, Prednisone administered every 14 days (R-CHOP-14) and supported with Pegfilgrastim. Cycle 5 of R-CHOP-14 will be delayed one week, and an interim PET/CT scan will be performed as close as possible (ie, day 17 to day 20) to the planned 5th cycle of R CHOP-14. Patients who have metabolically inactive disease (PET/CT-negative) will proceed to complete a further two cycles of R-CHOP-14 (total of 6 cycles) plus two doses of rituximab. Patients who display metabolically active disease (PET/CT-positive) will then receive treatment intensification with rituximab, Ifosfamide, Carboplatin and Etoposide (R-ICE) supported by Pegfilgrastim or Filgrastim for 3 cycles at intervals of 21 days. Peripheral blood stem cells will be collected following one of the cycles (typically the second or third) of R ICE. Subsequently, responding patients will undergo High Dose Chemotherapy (HDCT) with Zevalin-BEAM ( Z-BEAM) and autologous stem cell transplantation (ASCT).Dose is based on the individual patient Body Surface Area (BSA) calculation.
Intervention code [1] 3797 0
Treatment: Other
Intervention code [2] 3796 0
Treatment: Drugs
Comparator / control treatment
Active - PET+ patients recieve R-ICE and Z-BEAM Transplant. whereas the PET- patients will recieve R-CHOP chemotherapy only.
Control group
Active

Outcomes
Primary outcome [1] 5169 0
Primary objective and endpoint:
The primary objective is to demonstrate an absolute improvement of 25% in two-year progression-free survival (PFS) from 20% to 45% in those patients with advanced stage DLBCL who have been identified with a positive interim-treatment PET/CT scan and switched to early treatment intensification using R-ICE chemotherapy followed by HDCT/ASCT in comparison with historical outcomes.

The primary endpoint for this trial is progression-free survival (PFS).
Timepoint [1] 5169 0
progression-free survival (PFS). PFS is defined as the time from the interim PET/CT scan (after the 4th cycle of R-CHOP-14) to the first observation of disease progression or death from any cause.
Secondary outcome [1] 244845 0
Relapse rates. by a PET scan
Timepoint [1] 244845 0
2 years post completion of treatment regimen
Secondary outcome [2] 244844 0
Complete remission rates. disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy by a PET scan
Timepoint [2] 244844 0
2 years post completion of treatment regimen
Secondary outcome [3] 8702 0
Secondary objectives and endpoints:
Event-free survival (EFS). measured for all patients who have a positive interim PET/CT scan after the 4th cycle of treatment. Also using complete metabolic response(CMR), or non-CMR or partial metabolic response, using qualative and semi-qualitative analysis
Timepoint [3] 8702 0
2 years post completion of treatment regimen
Secondary outcome [4] 244846 0
Overall survival rates.
Timepoint [4] 244846 0
2 years post completion of treatment regimen

Eligibility
Key inclusion criteria
Inclusion criteria
1. Age 18 - 70 years
2. Male and female patients
3. Diagnosis of CD20-positive diffuse large B-cell lymphoma on biopsy
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
5. Low-intermediate, high-intermediate, high risk, or low risk disease with bulk (>7.5 cm)
6. Previously untreated (except for corticosteroids if required)
Patients considered suitable for dose-intense chemotherapy with R-CHOP-14 with Pegfilgrastim support
Eligible and fit for high dose chemotherapy with Z-BEAM and autologous stem-cell transplantation
Signed informed consent form
A positive baseline fluorodeoxyglucose(FDG) positron emission tomography(PET)
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria
1. Life-expectancy < 3 months
2. Transformed NonHodgkin lymphoma (NHL) or types of NHL other than DLBCL
3. Primary Central Nervous System (CNS) or gastrointestinal Mucosa-Associated Lymphoid Tissue (MALT)lymphoma
4. CD20-negative NHL
5. Documented Human Immunodeficiency Viris (HIV)
6. Seropositivity for Hepatitis B [Either 1. HbsAg (surface antigen) positive or 2. HbcAb (core antibody) positive and HbsAb (surface antibody) titre of < 100 iu/ml] unless clearly due to vaccination
7. Patients with good prognosis low risk disease (IPI = 0, 1) plus absence of bulk (= 7.5 cm).
8. Hypersensitivity to components of Zevalin including ibritumomab tiuxetan, Yttrium chloride, other murine proteins, or to any exipients
9. Pregnant woman
10. Previously treated lymphoma
11. Any serious active disease or co-morbid medical condition (according to investigator’s decision)
12. Non-compensated cardiac failure
13. Chronic lung disease with hypoxaemia
14. Severe psychiatric disease
15. Poor renal function (creatinine > 150 micromol/L), poor hepatic function (total bilirubin level > 30 mmol/L, transaminases > 2.5 maximum normal level) unless abnormalities are related to the lymphoma
16. Poor bone marrow reserve as defined by neutrophils < 1.5 x 109/L or platelets < 100 x 109/L, unless related to bone marrow infiltration
17. Any history of cancer during the last 5 years, with the exception of non-melanoma skin tumours or stage 0 (in situ) cervical carcinoma
18. Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/12/2008
Actual
20/07/2009
Date of last participant enrolment
Anticipated
Actual
20/12/2012
Date of last data collection
Anticipated
Actual
31/07/2015
Sample size
Target
162
Accrual to date
Final
162
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 4252 0
Other Collaborative groups
Name [1] 4252 0
Australasian Leukaemia and Lymphoma Group (ALLG)
Country [1] 4252 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group (ALLG)
Address
Level 2, 10 St Andrews Place
East Melbourne
3002
Victoria
Country
Australia
Secondary sponsor category [1] 3825 0
None
Name [1] 3825 0
Address [1] 3825 0
Country [1] 3825 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6304 0
Ethics committee address [1] 6304 0
Ethics committee country [1] 6304 0
Date submitted for ethics approval [1] 6304 0
01/11/2008
Approval date [1] 6304 0
05/03/2009
Ethics approval number [1] 6304 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29202 0
Address 29202 0
Country 29202 0
Phone 29202 0
Fax 29202 0
Email 29202 0
Contact person for public queries
Name 12359 0
Delaine Smith
Address 12359 0
Level 2, 10 St Andrews Place
East Melbourne
3002
Victoria
Country 12359 0
Australia
Phone 12359 0
+61 3 96563656
Fax 12359 0
+61 3 96561420
Email 12359 0
delaine.smith@petermac.org
Contact person for scientific queries
Name 3287 0
Associate Professor Mark Hertzberg
Address 3287 0
Department of Haematology
Westmead Hospital
Westmead
2145
New South Wales
Country 3287 0
Australia
Phone 3287 0
+610298456274
Fax 3287 0
Email 3287 0
mark_hertzberg@wmi.usyd.edu.au

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
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 info@allg.org.au


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
19922Study protocol  info@allg.org.au 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
SourceTitleYear of PublicationDOI
EmbaseRatios of T-cell immune effectors and checkpoint molecules as prognostic biomarkers in diffuse large B-cell lymphoma: A population-based study.2015https://dx.doi.org/10.1016/S2352-3026%2815%2900150-7
EmbaseEarly treatment intensification with R-ICE and 90Y-ibritumomab tiuxetan (Zevalin)-BEAM stem cell transplantation in patients with high-risk diffuse large B-cell lymphoma patients and positive interim PET after 4 cycles of R-CHOP-14.2017https://dx.doi.org/10.3324/haematol.2016.154039
EmbaseIntratumoral T-cell receptor repertoire is predictive of interim PET scan results in patients with diffuse large B-cell lymphoma treated with rituximab/cyclophosphamide/doxorubicin/prednisolone/vincristine (R-CHOP) chemoimmunotherapy.2021https://dx.doi.org/10.1002/cti2.1351
N.B. These documents automatically identified may not have been verified by the study sponsor.