To assess the feasibility and efficacy of 90Y-ibritumomab tiuxetan consolidation treatment after R-PECC chemotherapy as second or third line treatment in patients with refractory or relapsed aggressive B-cell NHL, after or not eligible for…
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
Feasibility and safety
Primary endpoint
- The incidence of grade >2 adverse events after treatment with 90Y-ibritumomab
tiuxetan.
Efficacy
Primary endpoint
- Failure free survival measured from the start of 90Y-ibritumomab tiuxetan
Secondary outcome
Feasibility and safety
Secondary endpoints
- Incidence and duration of hypoplasia after treatment with 90Y-ibritumomab
tiuxetan
- Incidence of adverse events (any grade) after treatment with 90Y-ibritumomab
tiuxetan
- Percentage of patients treated with R-PECC who proceed to 90Y-ibritumomab
tiuxetan treatment
- Incidence of adverse events (any grade) after treatment with R-PECC
Efficacy
Secondary endpoints
- Conversion to PET negative CR after 90Y-ibritumomab tiuxetan treatment of
patients who are PET positive before start of 90Y-ibritumomab tiuxetan
- Overall survival measured from the start of 90Y-ibritumomab tiuxetan
- Response rates to R-PECC and response duration
- Failure free survival and overall survival measured from the start of R-PECC
Background summary
Aggressive B-cell non-Hodgkin lymphoma (NHL) is the most common NHL and mainly
occurs in elderly patients.
The current treatment with immuno-chemotherapy results in a long-term disease
free survival of 51-70%. In a considerable part of the patients, the disease is
refractory or relapses. Elderly patients are not eligible for treatment with
high-dose chemotherapy followed by autologous stem cell transplantation because
of the toxicity of such treatment. The results of current second line
chemotherapy are disappointing. Most patients NHL will die within 2 years of
the recurrence of the disease.
Treatment with radio-immunotherapy is usually well tolerated and has a
relatively mild toxicity profile. In this trial a new treatment approach will
therefore be evaluated. The relapsed or refractory NHL will be treated with
oral chemotherapy courses (PECC) combined with rituximab. Patients with a
partial or complete remission subsequently receive a consolidation treatment
with radio-immunotherapy consisting of one administration of 90Y-ibritumomab
tiuxetan.
If this treatment approach is safe and leads to promising results, then it will
be compared to the current second line treatment regimens in a following trial.
Study objective
To assess the feasibility and efficacy of 90Y-ibritumomab tiuxetan
consolidation treatment after R-PECC chemotherapy as second or third line
treatment in patients with refractory or relapsed aggressive B-cell NHL, after
or not eligible for autologous stem cell transplantation.
Study design
This is a phase II prospective, multicenter, non-randomized clinical trial in
patients with relapsed or refractory aggressive B-cell NHL. Patients will be
treated with R-PECC chemotherapy.
After 2 and after 4 cycles of R-PECC patients will be evaluated for response.
All patients who have not at least attained a stable disease after 2 cycles of
R-PECC and a PR after 4 cycles of R-PECC will go off study. Patients in PR or
CR after 4 cycles of R-PECC will receive consolidation treatment with a single
dose of 90Y-ibritumomab tiuxetan.
Intervention
90Y-ibritumomab tiuxetan consolidation.
Study burden and risks
The new treatment consists of oral chemotherapy courses in combination with
rituximab. Patients who respond will subsequently be treated with
radio-immunotherapy consisting of one administration of 90Y-ibritumomab
tiuxetan. The aim is to prolong the disease free period. It is expected that
the total treatment will be acceptable for patients and that is has a
relatively mild toxicity.
Investigations and assessments are standard policy for these patients. No extra
investigations or assessments are required.
The risks for patients who participate in this trial are related to the
treatment and are standard.
De Boelelaan 1117
1081HV Amsterdam
NL
De Boelelaan 1117
1081HV Amsterdam
NL
Listed location countries
Age
Inclusion criteria
-Histologically confirmed aggressive B-cell NHL according to the World Health Organization (WHO) classification (see appendix A):
Follicular lymphoma grade 3b or Diffuse large B-cell lymphoma
-Refractory disease or histologically confirmed first or second relapse
(Refractory is defined as no response or partial remission according to CT. Patients in partial response (PR) can only be included in case of positive PET scan or positive biopsy)
-CD20 positive (assessed at 1st diagnosis or from fresh histology at confirmation of relapse or immunophenotyping of circulating CD20-positive NHL cells from peripheral blood)
-Current measurable disease, i.e. measurable in two perpendicular dimensions on physical examination or computerized tomography (CT) scan using standardized response criteria for NHL (Cheson et al19, 1999) (see appendix B)
-Age 18 years or older
-WHO performance status 0, 1 or 2 (see appendix E)
-Life expectancy of at least 3 months
-Absolute neutrophil count >1.5 x10^9/l and platelet count >100 x10^9/l (unless caused by NHL infiltration in the bone marrow)
-Written informed consent
Exclusion criteria
-Prior allogeneic stem cell transplantation
-Prior radioimmunotherapy
-Patients who have received chemotherapy or radiotherapy within 6 weeks prior to study entry or who have not recovered from toxicities related to prior therapies
-Eligibility for ASCT
-ASCT within 12 months of study entry
-Investigational drugs within 4 weeks prior to entry on this study or persistent toxic side effects of such therapy
-Treatment with external-beam radiation therapy to more than 25% of active bone marrow (see appendix F)
-A history of intolerance to rituximab
-Severe cardiac, pulmonary, neurological, psychiatric or metabolic disease which could compromise participation in the study, or serious underlying medical conditions which could impair the ability of the patient to participate in the trial
-Hepatic dysfunction, bilirubin or transaminases 2.5x upper normal limit or higher (unless caused by the NHL)
-Renal dysfunction, serum creatinine 180 umol/l or more or clearance 40 ml/min or less (unless caused by the NHL)
-Active uncontrolled infections
-Patients known to be HIV-positive
-Current or chronic hepatitis B or hepatitis C infection
-Symptomatic NHL localization in the central nervous system (CNS). Lumbal puncture is not required unless CNS involvement with NHL is clinically suspected
-Transformed indolent lymphoma
-Post-transplant lymphoproliferative disorder
-Pregnant or breast-feeding female patients. Negative serum pregnancy test at study is mandatory for female patients of childbearing potential
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 | EUCTR2006-007083-28-NL |
| CCMO | NL16852.078.07 |