Treatment of Patients With Diffuse Large B Cell Lymphoma Who Are Not Suitable for Anthracycline Containing Chemotherapy

NCT01679119 | Completed Phase 2 Results DMC

• 1 other identifier: UCL 11/0475
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 40

Brief 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. 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).

Conditions

Diffuse Large B Cell Lymphoma

Keywords

Diffuse large b cell lymphoma; Inotuzumab Ozogamicin; Gemcitabine; Rituximab; Cyclophosphamide; Vincristine; Prednisolone

Outcome Measures

Primary Outcomes (1)

• 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.

  At 2 years following date of randomisation.

Secondary Outcomes (8)

• Overall Response Rate

  Approximately 6 months after treatment start

• Overall Survival

  5 years from date of registration

• Treatment Toxicity

  7 months from beginning of treatment

• Quality of Life of Patients During and After Treatment

  Baseline, during treatment and 6 month and 2 year follow up

• Activities of Daily Living of Patients During and After Treatment

  Baseline, during treatment and 6 month and 2 year follow up

Study Arms (2)

IO-R-CVP

EXPERIMENTAL

Inotuzumab Ozogamicin plus Rituximab and CVP (Cyclophosphamide, vincristine \& prednisolone).

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).

Drug: Cyclophosphamide; Drug: Vincristine; Drug: Prednisolone; Drug: Rituximab; Drug: Gemcitabine

Interventions

Cyclophosphamide DRUG

Cyclophosphamide 750mg/m2 IV, given day 1

Gem-R-CVP; IO-R-CVP

Vincristine DRUG

Vincristine 1.4mg/m2(max 2mg)IV given day 1

Gem-R-CVP; IO-R-CVP

Prednisolone DRUG

Prednisolone 100mg OD Oral given days 1-5

Gem-R-CVP; IO-R-CVP

Rituximab DRUG

Rituximab 375mg/m2 IV given day 1

Also known as: MabThera

Gem-R-CVP; IO-R-CVP

Inotuzumab Ozogamicin DRUG

Inotuzumab Ozogamicin 0.8mg/m2 IV given on day 2

IO-R-CVP

Gemcitabine DRUG

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.)

Gem-R-CVP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University College, London: lead
• Pfizer: collaborator
• Cancer Research UK: collaborator

Study Sites (40)

Stoke Mandeville Hospital (including Wycombe Hospital)

Aylesbury, United Kingdom

Location

North Hampshire Hospital

Basingstoke, United Kingdom

Location

Royal United Hospital

Bath, United Kingdom

Location

Royal Bournemouth Hospital

Bournemouth, United Kingdom

Location

Bristol Oncology Centre

Bristol, United Kingdom

Location

West Suffolk Hospital

Bury St Edmunds, United Kingdom

Location

Kent and Canterbury Hospital

Canterbury, United Kingdom

Location

Castle Hill Hospital

Cottingham, United Kingdom

Location

University Hospital, Coventry

Coventry, United Kingdom

Location

Darent Valley Hospital

Dartford, United Kingdom

Location

Royal Devon & Exeter Hospital

Exeter, United Kingdom

Location

Medway Maritime Hospital

Gillingham, United Kingdom

Location

Beatson West of Scotland Cancer Centre (including Gartnavel Royal Hospital)

Glasgow, United Kingdom

Location

James Paget University Hospital

Great Yarmouth, United Kingdom

Location

Northwick Park Hospital

Harrow, United Kingdom

Location

Kettering General Hospital

Kettering, United Kingdom

Location

St James's University Hospital

Leeds, United Kingdom

Location

Leicester Royal Infirmary

Leicester, United Kingdom

Location

Aintree University Hospital

Liverpool, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, United Kingdom

Location

Guy's Hospital (including St Thomas's Hospital)

London, United Kingdom

Location

Royal Free Hospital

London, United Kingdom

Location

University College London Hospital

London, United Kingdom

Location

Luton and Dunstable Hospital

Luton, United Kingdom

Location

Christie Hospital

Manchester, United Kingdom

Location

Freeman Hospital

Newcastle, United Kingdom

Location

North Tyneside Hosptial (including Wansbeck Hospital and Hexham General Hospital)

North Shields, United Kingdom

Location

Norfolk and Norwich University Hospital

Norwich, United Kingdom

Location

Nottingham City Hospital

Nottingham, United Kingdom

Location

Princess Royal University Hospital

Orpington, United Kingdom

Location

Churchill Hospital

Oxford, United Kingdom

Location

Derriford Hospital

Plymouth, United Kingdom

Location

Queen's Hospital

Romford, United Kingdom

Location

Southampton General Hospital

Southampton, United Kingdom

Location

Kings Mill Hospital

Sutton in Ashfield, United Kingdom

Location

Torbay Hospital

Torquay, United Kingdom

Location

Royal Cornwall Hospital

Truro, United Kingdom

Location

Royal Hampshire County Hospital

Winchester, United Kingdom

Location

Worcester Royal Hospital (including Kidderminster Hospital and Alexandra Hospital)

Worcester, United Kingdom

Location

Wythenshawe Hospital (including Trafford General Hospital)

Wythenshawe, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Cyclophosphamide; Vincristine; Prednisolone; Rituximab; Inotuzumab Ozogamicin; Gemcitabine

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: INCA Trial Manager
• Organization: University College London

ctc.inca@ucl.ac.uk

02076799860

Study Officials

• Andrew McMillan

  Nottingham University Hospitals NHS Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2012
• First Posted: September 5, 2012
• Study Start: October 1, 2013
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2022
• Last Updated: March 17, 2026
• Results First Posted: March 17, 2026

Record last verified: 2025-05

Locations

GB (40)