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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2015 by University College, London
Sponsor:
Collaborators:
Pfizer
Cancer Research UK
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01679119
First received: July 23, 2012
Last updated: December 7, 2015
Last verified: December 2015
  Purpose

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).


Condition Intervention Phase
Diffuse Large B Cell Lymphoma
Drug: Cyclophosphamide
Drug: Vincristine
Drug: Prednisolone
Drug: Rituximab
Drug: Inotuzumab Ozogamicin
Drug: Gemcitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: At 2 years following date of randomisation. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall response rate [ Time Frame: Approximately 6 months after treatment start ] [ Designated as safety issue: No ]
    At the end of treatment

  • Overall Survival [ Time Frame: 5 years from date of registration ] [ Designated as safety issue: No ]
    Date of registration until death.

  • Treatment toxicity [ Time Frame: 7 months from beginning of treatment ] [ Designated as safety issue: Yes ]
    During treatment and follow up visits

  • Quality of life [ Time Frame: Baseline, during treatment and 6 month and 2 year follow up ] [ Designated as safety issue: No ]
  • Performance status post treatment [ Time Frame: 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. ] [ Designated as safety issue: No ]
  • Co-morbidities of patients [ Time Frame: Baseline ] [ Designated as safety issue: No ]

Estimated Enrollment: 132
Study Start Date: October 2013
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IO-R-CVP
Inotuzumab Ozogamicin plus Rituximab and CVP (Cyclophosphamide, vincristine & prednisolone).
Drug: Cyclophosphamide
Cyclophosphamide 750mg/m2 IV, given day 1
Drug: Vincristine
Vincristine 1.4mg/m2(max 2mg)IV given day 1
Drug: Prednisolone
Prednisolone 100mg OD Oral given days 1-5
Drug: Rituximab
Rituximab 375mg/m2 IV given day 1
Other Name: MabThera
Drug: Inotuzumab Ozogamicin
Inotuzumab Ozogamicin 0.8mg/m2 IV given on day 2
Active Comparator: Gem-R-CVP
Gemcitabine plus Rituximab and CVP (Cyclophosphamide, Vincristine and Prednisolone).
Drug: Cyclophosphamide
Cyclophosphamide 750mg/m2 IV, given day 1
Drug: Vincristine
Vincristine 1.4mg/m2(max 2mg)IV given day 1
Drug: Prednisolone
Prednisolone 100mg OD Oral given days 1-5
Drug: Rituximab
Rituximab 375mg/m2 IV given day 1
Other Name: MabThera
Drug: Gemcitabine
Gemcitabine 1g/m2 IV given day 1 and day 8

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).
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • 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) 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
  • No active malignant disease other than non-melanotic skin cancer, superficial bladder cancers or carcinoma in-situ of the uterine cervix in the last 5 years
  • 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

Exclusion criteria:

  • Symptomatic central nervous system or meningeal involvement by DLBCL
  • Previous diagnosis of low grade lymphoma.
  • 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
  • Patients with a history of severe allergic/anaphylactic reaction to any humanised monoclonal antibody
  • Patients with serious active infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01679119

Contacts
Contact: INCA Trial Coordinator + 44 2076799860 ctc.inca@ucl.ac.uk

Locations
United Kingdom
Stoke Mandeville Hospital (including Wycombe Hospital) Recruiting
Aylesbury, United Kingdom
Contact: Beena Pushkaran         
North Hampshire Hospital Recruiting
Basingstoke, United Kingdom
Contact: Alison Milne         
Royal United Hospital Recruiting
Bath, United Kingdom
Contact: Christopher Knechtli         
Bristol Oncology Centre Recruiting
Bristol, United Kingdom
Contact: Lisa Lowry         
West Suffolk Hospital Recruiting
Bury St Edmunds, United Kingdom
Contact: Mamtha Karanth         
Darent Valley Hospital Recruiting
Dartford, United Kingdom
Contact: Tariq Shafi         
Medway Maritime Hospital Recruiting
Gillingham, United Kingdom
Contact: Maadh Abdul-Wahab Aldouri         
Beatson West of Scotland Cancer Centre Recruiting
Glasgow, United Kingdom
Contact: Pam McKay         
James Paget University Hospital Recruiting
Great Yarmouth, United Kingdom
Contact: Shalal Sadullah         
Northwick Park Hospital Recruiting
Harrow, United Kingdom
Contact: Nicki Panoskaltsis         
Huddersfield Royal Infirmary (including Calderdale Royal Hospital) Recruiting
Huddersfield, United Kingdom
Contact: Kate Rothwell         
Kent and Canterbury Hospital Recruiting
Kent, United Kingdom
Contact: Kamiran Saied         
Kettering General Hospital Recruiting
Kettering, United Kingdom
Contact: Matthew Lyttelton         
St James's University Hospital Recruiting
Leeds, United Kingdom
Contact: Cathy Burton         
Leicester Royal Infirmary Recruiting
Leicester, United Kingdom
Contact: Fiona Miall         
Royal Liverpool University Hospital Recruiting
Liverpool, United Kingdom
Contact: Nagesh Kalakonda         
Guy's Hospital (including St Thomas's Hospital) Recruiting
London, United Kingdom
Contact: Paul Fields         
Royal Free Hospital Recruiting
London, United Kingdom
Contact: Kate Cwynarski         
University College London Hospital Recruiting
London, United Kingdom
Contact: Kirit Ardeshna         
Luton and Dunstable Hospital Recruiting
Luton, United Kingdom
Contact: Rahul Joshi         
Christie Hospital Recruiting
Manchester, United Kingdom
Contact: Kim Linton         
Manchester Royal Infirmary Recruiting
Manchester, United Kingdom
Contact: Chiara Lobetti         
Freeman Hospital Recruiting
Newcastle, United Kingdom
Contact: Anne Lennard         
Norfolk and Norwich University Hospital Recruiting
Norwich, United Kingdom
Contact: Jennie Wimperis         
Nottingham City Hospital Recruiting
Nottingham, United Kingdom
Contact: Andrew McMillan         
Princess Royal University Hospital Recruiting
Orpington, United Kingdom
Contact: Mansour Ceesay         
Churchill Hospital Recruiting
Oxford, United Kingdom
Contact: Graham Collins         
Derriford Hospital Recruiting
Plymouth, United Kingdom
Contact: Simon Rule         
Queen's Hospital Recruiting
Romford, United Kingdom
Contact: Alison Brownell         
Southampton General Hospital Recruiting
Southampton, United Kingdom
Contact: Andy Davies         
Kings Mill Hospital Recruiting
Sutton-in-Ashfield, United Kingdom
Contact: Steve Jones         
Torbay Hospital Recruiting
Torquay, United Kingdom
Contact: Deborah Turner         
Royal Cornwall Hospital Recruiting
Truro, United Kingdom
Contact: Anton Kruger         
Royal Hampshire County Hospital Recruiting
Winchester, United Kingdom
Contact: Katherine Lowndes         
New Cross Hospital Recruiting
Wolverhampton, United Kingdom
Contact: Abraham Jacob         
Wythenshawe Hospital (including Trafford General Hospital) Recruiting
Wythenshawe, United Kingdom
Contact: Simon Watt         
Sponsors and Collaborators
University College, London
Pfizer
Cancer Research UK
Investigators
Principal Investigator: Andrew McMillan Nottingham University Hospitals NHS Trust
  More Information

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01679119     History of Changes
Other Study ID Numbers: UCL 11/0475 
Study First Received: July 23, 2012
Last Updated: December 7, 2015
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University College, London:
Diffuse large b cell lymphoma
Inotuzumab Ozogamicin
Gemcitabine
Rituximab
Cyclophosphamide
Vincristine
Prednisolone

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Gemcitabine
Cyclophosphamide
Rituximab
Prednisolone
Methylprednisolone Hemisuccinate
Vincristine
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on September 30, 2016