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

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ClinicalTrials.gov Identifier: NCT01679119
Recruitment Status : Active, not recruiting
First Posted : September 5, 2012
Last Update Posted : April 18, 2019
Sponsor:
Collaborators:
Pfizer
Cancer Research UK
Information provided by (Responsible Party):
University College, London

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).


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

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 132 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : October 2013
Actual Primary Completion Date : March 2019
Estimated Study Completion Date : September 2021


Arm Intervention/treatment
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 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.)




Primary Outcome Measures :
  1. Progression free survival [ Time Frame: At 2 years following date of randomisation. ]
    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 :
  1. Overall response rate [ Time Frame: Approximately 6 months after treatment start ]
    At the end of treatment

  2. Overall Survival [ Time Frame: 5 years from date of registration ]
    Date of registration until death.

  3. Treatment toxicity [ Time Frame: 7 months from beginning of treatment ]
    During treatment and follow up visits

  4. Quality of life of patients during and after treatment [ Time Frame: Baseline, during treatment and 6 month and 2 year follow up ]
    QoL questionnaires (EORTC QLQ-C30; Quality of life of cancer patients; 30 questions) to be completed by patient at time points listed below

  5. Activities of Daily Living of patients during and after treatment [ Time Frame: Baseline, during treatment and 6 month and 2 year follow up ]
    Activities of Daily Living questionnaire (ADL) to be completed by patient at time points listed below (6 questions about ability to undertake self-care)

  6. Instrumental Activities of Daily Living of patients during and after treatment [ Time Frame: Baseline, during treatment and 6 month and 2 year follow up ]
    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)

  7. 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. ]
    Performance status to be measured by investigator at time points listed below

  8. Co-morbidities of patients [ Time Frame: Baseline ]
    Details of co-morbidities to be recorded at point of randomisation by investigator



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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) 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01679119


Locations
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Sponsors and Collaborators
University College, London
Pfizer
Cancer Research UK
Investigators
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Principal Investigator: Andrew McMillan Nottingham University Hospitals NHS Trust
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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01679119    
Other Study ID Numbers: UCL 11/0475
First Posted: September 5, 2012    Key Record Dates
Last Update Posted: April 18, 2019
Last Verified: April 2019
Keywords provided by University College, London:
Diffuse large b cell lymphoma
Inotuzumab Ozogamicin
Gemcitabine
Rituximab
Cyclophosphamide
Vincristine
Prednisolone
Additional relevant MeSH terms:
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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
Prednisolone
Cyclophosphamide
Rituximab
Vincristine
Inotuzumab Ozogamicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents