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

NCT01679119

Last updated date
Study Location
Stoke Mandeville Hospital (including Wycombe Hospital)
Aylesbury, , , United Kingdom
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Diffuse Large B Cell Lymphoma
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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


- Patients with a history of severe allergic/anaphylactic reaction to any humanised
monoclonal antibody


- Patients with serious active infection

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Diffuse Large B Cell LymphomaTreatment of Patients With Diffuse Large B Cell Lymphoma Who Are Not Suitable for Anthracycline Containing Chemotherapy
NCT01679119
  1. Aylesbury,
  2. Basingstoke,
  3. Bath,
  4. Bournemouth,
  5. Bristol,
  6. Bury St Edmunds,
  7. Canterbury,
  8. Cottingham,
  9. Coventry,
  10. Dartford,
  11. Exeter,
  12. Gillingham,
  13. Glasgow,
  14. Great Yarmouth,
  15. Harrow,
  16. Kettering,
  17. Leeds,
  18. Leicester,
  19. Liverpool,
  20. Liverpool,
  21. London,
  22. London,
  23. London,
  24. Luton,
  25. Manchester,
  26. Newcastle,
  27. North Shields,
  28. Norwich,
  29. Nottingham,
  30. Orpington,
  31. Oxford,
  32. Plymouth,
  33. Romford,
  34. Southampton,
  35. Sutton-in-Ashfield,
  36. Torquay,
  37. Truro,
  38. Winchester,
  39. Worcester,
  40. Wythenshawe,
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Treatment of Patients With Diffuse Large B Cell Lymphoma Who Are Not Suitable for Anthracycline Containing Chemotherapy
Official Title  ICMJE 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
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).

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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Diffuse Large B Cell Lymphoma
Intervention  ICMJE
  • 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
  • Drug: Gemcitabine
    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 Arms  ICMJE
  • Experimental: IO-R-CVP
    Inotuzumab Ozogamicin plus Rituximab and CVP (Cyclophosphamide, vincristine & prednisolone).
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Vincristine
    • Drug: Prednisolone
    • Drug: Rituximab
    • Drug: Inotuzumab Ozogamicin
  • Active Comparator: Gem-R-CVP
    Gemcitabine plus Rituximab and CVP (Cyclophosphamide, Vincristine and Prednisolone).
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Vincristine
    • Drug: Prednisolone
    • Drug: Rituximab
    • Drug: Gemcitabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: December 7, 2015)
132
Original Estimated Enrollment  ICMJE
 (submitted: August 30, 2012)
154
Estimated Study Completion Date  ICMJE September 2021
Actual Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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) 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

Exclusion criteria:

  • 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
  • Patients with a history of severe allergic/anaphylactic reaction to any humanised monoclonal antibody
  • Patients with serious active infection
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01679119
Other Study ID Numbers  ICMJE UCL 11/0475
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University College, London
Study Sponsor  ICMJE University College, London
Collaborators  ICMJE
  • Pfizer
  • Cancer Research UK
Investigators  ICMJE
Principal Investigator:Andrew McMillanNottingham University Hospitals NHS Trust
PRS Account University College, London
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP