Diffuse Large B Cell LymphomaPhase 2INCANCT01679119
Treatment of Patients With Diffuse Large B Cell Lymphoma Who Are Not Suitable for Anthracycline Containing Chemotherapy
A Phase 2 study testing Cyclophosphamide, Vincristine and Prednisolone in people with Diffuse Large B Cell Lymphoma, run by University College, London at 40 sites in United Kingdom.
Trial summary
The purpose of this trial is to compare the efficacy and safety of Inotuzumab Ozogamicin in combination with R-CVP with that of R-G-CVP for the treatment of Diffuse Large B Cell Lymphoma (DLBCL) in a population of patients not suitable for anthracycline based chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B Cell Lymphoma
- What is being tested?
- Cyclophosphamide, Vincristine and Prednisolone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 129 participants
- Where
- 40 sitesUnited Kingdom
- Study dates
- Oct 2013to Mar 2022
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed written consent for the trial
- Histologically proven diffuse large B cell lymphoma (DLBCL) according to the current World Health Organisation (WHO) classification including all morphological variants. The B cell nature of the proliferation must be verified by demonstration of CD20 positivity. A concurrent (synchronous) diagnosis of low grade lymphoma (e.g. on bone marrow trephine or presence of both low grade and DLBCL in a lymph node biopsy) or previous diagnosis of low grade lymphoma which hasn't been treated with a systemic therapy is permitted
- Bulky Stage IA (lymph node or lymph node mass ≥ 10cm in maximum diameter), stage IB, stage II, stage III and stage IV disease
- ECOG performance status 0-2
- Measurable disease
- Age 18 ≥ years
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- Adequate contraceptive precautions for all patients of childbearing potential
- History of malignant disease diagnosed at any time in the past with completed radical treatment and the risk of relapsing within the next 5 years is <10%. Patients previously treated should be free of sequelae of treatment which would compromise the delivery of study drugs as compared with other eligible patients.
- No previous chemotherapy, radiotherapy or other investigational drug for this indication - previous corticosteroids up to a dose equivalent to prednisolone 1mg/kg/day for up to 14 days are permitted prior to randomisation EITHER
- Unsuitable for anthracycline-containing chemotherapy due to impaired cardiac function defined by an ejection fraction of ≤ 50% OR Left ventricle ejection fraction > 50% but in the presence of significant co-morbidities (diabetes mellitus, hypertension or ischaemic heart disease) precluding anthracycline-containing chemotherapy as determined by treating physician. Co-morbidities must be documented on the randomisation form and CIRS score recorded
- Adequate bone marrow function (Platelets > 100x109/l, WBC > 3.0x109/l, Neutrophils > 1.5x109/l) at time of study entry unless attributed to bone marrow infiltration by DLBCL
- Life expectancy > 3 months
Who cannot join
- Symptomatic central nervous system or meningeal involvement by DLBCL
- Previous diagnosis of low grade lymphoma which has been treated with a systemic therapy
- Non-bulky stage IA disease
- ECOG performance status 3-4
- History of chronic liver disease or suspected alcohol abuse
- Serum bilirubin greater than upper limit of normal unless attributable to Gilberts syndrome or haemolysis
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- Alanine and/or aspartate aminotransferase levels (ALT and/or AST) and alkaline phosphatase (ALP) greater than 2.5 times the upper limit of normal
- Glomerular filtration rate (GFR) < 30ml/min. GFR calculated by Cockroft-Gault (not eGFR).
- Serological evidence of active hepatitis B or C infection whether acute or chronic (defined as positive anti-HCV serology; positive HBsAg). All positive HBcAb results should also be excluded on safety grounds regardless of HBsAg or HBV DNA status. Antibodies to Hepatitis B surface antigen (anti-HBs) due to a history of past vaccination is acceptable
- Known history of HIV seropositive status
- Patients with a history of Venoocclusive Disease (VOD) and Sinusoidal Obstructive Syndrome (SOS)
- Patients with a screening of QTcF interval >470msec
- Medical or psychiatric conditions compromising the patient's ability to give informed consent
- Women who are pregnant or lactating
- LVEF > 50% in the absence of significant co-morbidities that preclude anthracycline use
- Patients with a history of severe allergic/anaphylactic reaction to any humanised monoclonal antibody
- Patients with serious active infection
Trial locations and contacts
40 sites in 1 country.
40 sites in 1 country
United Kingdom40 sites
Stoke Mandeville Hospital (including Wycombe Hospital)
Aylesbury
North Hampshire Hospital
Basingstoke
Royal United Hospital
Bath
Royal Bournemouth Hospital
Bournemouth
Bristol Oncology Centre
Bristol
West Suffolk Hospital
Bury St Edmunds
Kent and Canterbury Hospital
Canterbury
Castle Hill Hospital
Cottingham
University Hospital, Coventry
Coventry
Darent Valley Hospital
Dartford
Royal Devon & Exeter Hospital
Exeter
Medway Maritime Hospital
Gillingham
Beatson West of Scotland Cancer Centre (including Gartnavel Royal Hospital)
Glasgow
James Paget University Hospital
Great Yarmouth
Northwick Park Hospital
Harrow
Kettering General Hospital
Kettering
St James's University Hospital
Leeds
Leicester Royal Infirmary
Leicester
Aintree University Hospital
Liverpool
Royal Liverpool University Hospital
Liverpool
Guy's Hospital (including St Thomas's Hospital)
London
Royal Free Hospital
London
University College London Hospital
London
Luton and Dunstable Hospital
Luton
Christie Hospital
Manchester
Freeman Hospital
Newcastle
North Tyneside Hosptial (including Wansbeck Hospital and Hexham General Hospital)
North Shields
Norfolk and Norwich University Hospital
Norwich
Nottingham City Hospital
Nottingham
Princess Royal University Hospital
Orpington
Churchill Hospital
Oxford
Derriford Hospital
Plymouth
Queen's Hospital
Romford
Southampton General Hospital
Southampton
Kings Mill Hospital
Sutton in Ashfield
Torbay Hospital
Torquay
Royal Cornwall Hospital
Truro
Royal Hampshire County Hospital
Winchester
Worcester Royal Hospital (including Kidderminster Hospital and Alexandra Hospital)
Worcester
Wythenshawe Hospital (including Trafford General Hospital)
Wythenshawe
About this study
Official title: A Randomised Phase II Trial of Inotuzumab Ozogamicin Plus Rituximab & CVP (IO-R-CVP) vs Gemcitabine Plus Rituximab & CVP (Gem-R-CVP) for the First Line Treatment of Patients With DLBCL Who Are Not Suitable for Anthracycline Containing Chemotherapy
The purpose of this trial is to compare the efficacy and safety of Inotuzumab Ozogamicin in combination with R-CVP with that of R-G-CVP for the treatment of Diffuse Large B Cell Lymphoma (DLBCL) in a population of patients not suitable for anthracycline based chemotherapy.
There is no standard of care for the treatment of this group of patients. If demonstrated to be efficacious and safe to deliver this regimen will be further tested in a phase III trial to determine whether this should become the standard of care amongst patients with DLBCL not fit for anthracycline (R-CHOP).
Read the detailed description
The incidence of DLBCL is increasing and with an expanding elderly population, the incidence will continue to rise. Given that about 40% of cases of DLBCL occur in patients aged over 70 and the number of co-mobilities increases with age, research to investigate the optimal treatment of DLBCL in this group of patients is needed. R-CHOP remains the standard of care for the majority of patients with DLBCL, anthracycline use is precluded in a proportion of these patients by a high risk of developing cardiotoxicity, especially congestive cardiac failure. Currently there is no standard of care for patients who are unfit for anthracycline treatment. It has been routine to omit the doxorubicin from R-CHOP, giving R-CVP instead. However the outcome for patients treated with R-CVP is poor and attempts have been made to replace the doxorubicin with alternative agents. The trial will compare an experimental arm consisting of Inotuzumab Ozogamicin added to the standard immunochemotherapy regimen of rituximab, cyclophosphamide, vincristine and prednisolone (R-CVP) with the control arm of gemcitabine added to the same combination (Gem-R-CVP).
- Conditions
- Diffuse Large B Cell Lymphoma
- Being tested
- Cyclophosphamide, Vincristine, Prednisolone, Rituximab, Inotuzumab Ozogamicin
- Keywords
- Diffuse large b cell lymphoma, Inotuzumab Ozogamicin, Gemcitabine, Rituximab, Cyclophosphamide, Vincristine, Prednisolone
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Cyclophosphamide 750mg/m2 IV, given day 1
VincristineDrug
Vincristine 1.4mg/m2(max 2mg)IV given day 1
PrednisoloneDrug
Prednisolone 100mg OD Oral given days 1-5
RituximabDrug
Also called MabThera
Rituximab 375mg/m2 IV given day 1
Inotuzumab OzogamicinDrug
Inotuzumab Ozogamicin 0.8mg/m2 IV given on day 2
GemcitabineDrug
Gemcitabine up to 1g/m2 IV given day 1 and day 8 (Patients with ECOG PS 0-1: starting dose: 875mg/m2 (1st cycle). If tolerated can be escalated to 1g/m2 in cycle 2 and subsequent cycles. Patients with ECOG PS 2: starting dose 750mg/m2 (1st cycle). If tolerated can be escalated to 875mg/m2 in cycle 2 and then escalated to 1g/m2 in cycle 3 and subsequent cycles.)
| Study group | Role | What they receive |
|---|---|---|
| IO-R-CVP | Experimental | Inotuzumab Ozogamicin plus Rituximab and CVP (Cyclophosphamide, vincristine \& prednisolone). Receives: Drug: Cyclophosphamide; Drug: Vincristine; Drug: Prednisolone; Drug: Rituximab; Drug: Inotuzumab Ozogamicin |
| Gem-R-CVP | Active comparator | Gemcitabine plus Rituximab and CVP (Cyclophosphamide, Vincristine and Prednisolone). Receives: Drug: Cyclophosphamide; Drug: Vincristine; Drug: Prednisolone; Drug: Rituximab; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
Progression free survival rate and will be analysed using Kaplan-Meier survival analysis. PFS time will be measured from date of randomisation until progression or death.
Measured: At 2 years following date of randomisation.
Secondary outcomes (8)
Overall Response Rate
At the end of treatment
Measured: Approximately 6 months after treatment start
Overall Survival
Date of registration until death.
Measured: 5 years from date of registration
Treatment Toxicity
During treatment and follow up visits
Measured: 7 months from beginning of treatment
Quality of Life of Patients During and After Treatment
QoL questionnaires (EORTC QLQ-C30; Quality of life of cancer patients; 30 questions) to be completed by patient at time points listed below
Measured: Baseline, during treatment and 6 month and 2 year follow up
Activities of Daily Living of Patients During and After Treatment
Activities of Daily Living questionnaire (ADL) to be completed by patient at time points listed below (6 questions about ability to undertake self-care)
Measured: Baseline, during treatment and 6 month and 2 year follow up
Instrumental Activities of Daily Living of Patients During and After Treatment
Instrumental Activities of Daily Living questionnaire (IADL) to be completed by patient at time points listed below (8 questions about ability to undertake daily activities/self-care)
Measured: Baseline, during treatment and 6 month and 2 year follow up
Performance Status Post Treatment
Performance status to be measured by investigator at time points listed below
Measured: Baseline, every 21 days for 8 cycles, 5 1/2 months at the end of treatment and then up to 3 years after the end of treatment.
Co-morbidities of Patients
Details of co-morbidities to be recorded at point of randomisation by investigator
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2012 (estimated)
- Study startOct 2013
- Primary completionMar 2019
- Study completionMar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diffuse Large B Cell LymphomaStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 129 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, Cancer Research UK
- Responsible party
- Sponsor
- Investigators
- Andrew McMillan, Principal investigator, Nottingham University Hospitals NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01679119
- Sponsor's protocol ID
- UCL 11/0475
- Acronym
- INCA
- Status last verified
- May 2025
- First submitted
- 23 Jul 2012
- Last updated
- 7 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes