To evaluate the efficacy ofa. early intensification of rituximab combined with 2-weekly CHOP+G-CSF (R-CHOP14) in remission induction treatment in comparison to standard R-CHOP14b. maintenance treatment with rituximab in patients in remission after R…
ID
Source
Brief title
Condition
- Lymphomas non-Hodgkin's B-cell
- Lymphomas non-Hodgkin's B-cell
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
First randomization:
Primary endpoint
* Response rate (complete remission and FDG-PET negative partial remission or
unconfirmed complete remission)
Second randomization:
Primary endpoint
* Failure free survival (measured from the date of second randomization)
The definition of failure used in failure free survival (whichever comes first)
will be:
- No response on induction treatment (whereby response is defined as CR or PET
negative
PR/CRu)
- Relapse
- Death (from any cause)
Secondary outcome
First randomization:
Secondary endpoints
* Failure free survival measured from the date of registration. Patients
still alive or lost to follow up are censored at the last day they were known
to be alive
* Overall survival measured from the time of registration
* Time to reach response
* Toxicity
Second randomization:
Secondary endpoints
* Overall survival
* Toxicity
The definition of failure used in failure free survival (whichever comes first)
will be:
- No response on induction treatment (whereby response is defined as CR or PET
negative
PR/CRu)
- Relapse
- Death (from any cause)
Background summary
Diffuse large B-cell lymphoma is the most common lymphoma and occurs in both
young and elderly patients, however most frequently in elderly patients.
Current treatment with 2-weekly rituximab-CHOP courses results in an event free
survival of 51%-70%. Therefore, a relapse is seen in a large part of the
patients. Approximately 50% of the young patients with primary refractory
disease or relapse can be salvaged with high dose chemotherapy followed by
autologous stem cell transplantation. Elderly patients cannot be cured with
salvage therapy. Most relapse patients die within two years. Current overall
survival rate is 63% -80%. Thus, treatment results are not satisfactory.
Therefore, novel strategies must be explored.
Study objective
To evaluate the efficacy of
a. early intensification of rituximab combined with 2-weekly CHOP+G-CSF
(R-CHOP14) in remission induction treatment in comparison to standard R-CHOP14
b. maintenance treatment with rituximab in patients in remission after R-CHOP14
in comparison to no further treatment
Study design
Prospective, randomised, multi-center study.
The first part is the remission induction therapy and consists of 6 cycles
(elderly patients) or 8 cycles (young patients) of CHOP given every 2 weeks. In
addition rituximab will be given on day one or on day one and eight of the
first 4 CHOP cycles. For young patients, rituximab will be given on day one of
the last 4 CHOP cycles. For the elderly patients, rituximab will be given on
day one of the 5th CHOP cycle, and on day 1, 15 and day 29 of the 6th CHOP
cycle.
The second part of the study is the maintenance therapy and consists of 12x
rituximab once every 8 weeks for 2 years for those who randomised for
maintenance therapy. The other 50% of the patients will receive no maintenance
treatment.
Intervention
intravenous rituximab
Study burden and risks
Patients in the experimental arm of the study must pay 4 more visits to the
outpatient clinic to receive the 4 extra gifts of rituximab. This also applies
to the patients randomising for the 12 gifts of rituximab during the
maintenance phase. The extra rituximab gifts may induce a larger decrease of
the serum immunoglobulins. This may result in an increased risk for infections.
In the protocol mandatory measurements to prevent complications are
described.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
For first randomization:, - Patients with a confirmed histologic diagnosis of
diffuse large B-cell lymphoma (DLBCL) based upon a representative histology
specimen according to the WHO classification (see appendix A), - DLBCL must be
CD20 positive, - Ann Arbor stages II-IV (see appendix C), - Age 18-65 years and
age-adjusted IPI 1-3 OR age 66-80 years and age-adjusted IPI 0-3 , - WHO
performance status 0 - 2 (see appendix E) , - Written informed consent, For
second randomization:, Patients achieving a CR (or FDG-PET negative PR/CRu)
after 6 (elderly) or 8 (young patients) cycles of R-CHOP14 will be randomized
to maintenance treatment with rituximab or no further treatment., - Patients in
complete remission or FDG-PET negative partial remission/unconfirmed complete
remission at least 4 weeks after the last cycle of R-CHOP14 (including last
rituximab administration), - Time interval since last cycle of R-CHOP14
(including last rituximab administration) between 4 and 8 weeks, - No
rituximab-related adverse event necessitating stopping of rituximab
administration, - No active infection, - Written informed consent
Exclusion criteria
-Age 18-65 (inclusive) years and aa-IPI 0 (no risk factors), -Intolerance of
exogenous protein administration, -Severe cardiac dysfunction (NYHA
classification III-IV, see appendix F) or LVEF < 45%, - Congestive heart
failure or symptomatic coronary artery disease or cardiac arrhythmias not well
controlled with medication. Myocardial infarction during the last 6 months , -
Severe pulmonary dysfunction (vital capacity or diffusion capacity < 50% of
predicted value) unless clearly related to NHL involvement, - Patients with
uncontrolled asthma or allergy, requiring systemic steroid treatment , -
Significant hepatic dysfunction (total bilirubin >= 30mmol/l or
transaminases >= 2.5 x upper normal limit), unless related to NHL , -
Significant renal dysfunction (serum creatinine >= 150 umol/l or clearance
<= 60 ml/min), unless related to NHL, - Clinical signs of severe cerebral
dysfunction, - Suspected or documented Central Nervous System involvement by
NHL, - Patients with a history of uncontrolled seizures, central nervous system
disorders or psychiatric disability judged by the investigator to be clinically
significant and adversely affecting compliance to study drugs, - Testicular
DLBCL, - Primary mediastinal B cell lymphoma, - Transformed indolent lymphoma,
- (EBV) post-transplant lymphoproliferative disorder, - Secondary lymphoma
after previous chemotherapy or radiotherapy, - Major surgery, other than
diagnostic surgery, within the last 4 weeks, - Patients with active
uncontrolled infections, - Patients known to be HIV-positive, - Active chronic
hepatitis B or C infection, - Serious underlying medical conditions, which
could impair the ability of the patient to participate in the trial (e.g.
ongoing infection, uncontrolled diabetes mellitus, gastric ulcers, active
autoimmune disease), - Life expectancy < 6 months, - Prior treatment with
chemotherapy, radiotherapy or immunotherapy for this lymphoma, except a short
course of prednisone (< 1 week) and/or cyclophosphamide (< 1 week and not
in excess of 900 mg/m2 cumulative) or local radiotherapy in order to control
life threatening tumor related symptoms, - History of active cancer during the
past 5 years, except basal carcinoma of the skin or stage 0 cervical carcinoma
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-005174-42-NL |
| Other | ISRTCN82286322 |
| CCMO | NL15414.078.07 |