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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 not yet open for participant recruitment.
Verified May 2013 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: May 9, 2013
Last verified: May 2013
History of Changes
  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:

MedlinePlus related topics: Lymphoma
U.S. FDA Resources

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: 154
Study Start Date: June 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2015 (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
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria for registration:

  • 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
  • Bulky Stage IA (lymph node or lymph node mass ≥ 10cm in maximum diameter), stage IB, stage II, stage III and stage IV disease
  • Measurable disease
  • Age 18 ≥ years
  • Adequate contraceptive precautions for all patients of childbearing potential
  • No active malignant disease other than non-melanotic skin cancer 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 registration 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 registration 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

Inclusion Criteria for randomisation:-

  • ECOG performance status 0-2 after steroid pre-phase
  • Continue to meet all inclusion criteria detailed in inclusion registration section.

Exclusion criteria for registration:

  • Symptomatic central nervous system or meningeal involvement by DLBCL
  • Previous diagnosis of low grade lymphoma. A concurrent (synchronous) diagnosis of low grade lymphoma (e.g. on bone marrow trephine) is permitted
  • Non-bulky stage IA disease
  • History of chronic liver disease or suspected alcohol abuse
  • Serum bilirubin greater than upper limit of normal unless attributable to lymphoma or Gilberts syndrome
  • Glomerular filtration rate (GFR) < 30ml/min. GFR calculated by Cockroft-Gault (not eGFR).
  • Positive test results for chronic hepatitis B or C infection (defined as positive HBsAg/HCsAg and/or HBcAb/HCcAb). Antibodies to Hepatitis B surface antigen (anti-HBs) due to a history of past vaccination is acceptable
  • Known history of HIV seropositive status
  • 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

Exclusion criteria for randomisation:-

  • ECOG performance status 3 or 4 after steroid pre-phase
  • Meets one or more of the exclusion criteria detailed in exclusion registration section.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01679119

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

Sponsors and Collaborators
University College, London
Pfizer
Cancer Research UK
Investigators
Principal Investigator: Andrew McMillan Nottingham University Hospitals NHS Trust
  More Information

No publications provided

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: May 9, 2013
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
Cyclophosphamide
Gemcitabine
Rituximab
Prednisolone
Methylprednisolone Hemisuccinate
 Vincristine
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013