Evaluation of intensive therapy for relapsed B-cell lymphoma with CNS localisation. Treatment includes:a. intrathecal administration of rituximab, B. combining R-DHAP with high dose methotrexate intravenously.The following endpoints will be…
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
1.Progression-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.
Secondary outcome
2.Response to R-DHAP-MTX.
3.Overall survival.
4.Toxicity
5.Percentage of patients transplanted.
Background summary
Patients with a recurrent aggressive B-cell lymphoma with CNS localisation have
a poor prognosis in the current treatment setting. This study will assess a new
treatment option (intrathecal rituximab administration) in combination with
intensive chemotherapy to increase treatment efficacy.
Study objective
Evaluation of intensive therapy for relapsed B-cell lymphoma with CNS
localisation. Treatment includes:
a. intrathecal administration of rituximab,
B. combining R-DHAP with high dose methotrexate intravenously.
The following endpoints will be evaluated: progression free survival, response
rate and overall survival.
Study design
Prospective multicenter, phase II
Intervention
Intrathecal rituximab
Systemic high dose methotrexate
Study burden and risks
The intensive treatment requires several hospitalizations for administration of
the chemotherapy as well as monitoring of potential complications as is
normally required for all other regular/standard intensive treatments for
hemato-oncological malignancies. Intensive chemotherpeutic treatment may be
complicated by complications of infectious nature. High dose methotrexate may
cause renal insufficiency. There are no serious complications known of
intrathecal rituximab administration in the dosage used in this study. The
experience however is limited.
De Boelelaan 1117
1081 HV Amsterdam
NL
De Boelelaan 1117
1081 HV Amsterdam
NL
Listed location countries
Age
Inclusion criteria
*Diagnosis of aggressive malignant B-cell lymphoma based upon a representative -histology specimen according to the WHO classification (see appendix A):
*follicular lymphoma grade III
*diffuse large B-cell lymphoma
Prior *low-grade* lymphoma with histologically proven transformation to follicular lymphoma grade III or DLBCL is also permitted.
*CD 20 positive
*First progression or relapse with CNS localisation (see below) without or with systemic relapse (preferably histologically proven). *Progressive* includes patients who have progressive disease (PD), without prior response and patients who have progression after first PR.
*Diagnosis of CNS localisation based on at least one of the following:
-unequivocal morphological and/or immunophenotypical evidence of CSF lymphoma
-clinical AND MRI evidence of leptomeningeal localisation
-brain parenchymal lesion showing homogeneous contrast enhancement suspect for lymphoma, concurrently with systemic progression or recurrence
-biopsy-proven brain parenchymal NHL localisation of previously diagnosed systemic NHL
*Age 18-65 years inclusive
*WHO performance status 0 - 2 (see appendix F) with or without administration of steroids
*Written informed consent according to the centre*s requirements
*Negative pregnancy test in women of reproductive potential
Exclusion criteria
*History of intolerance of exogenous protein administration
*Severe cardiac dysfunction (NYHA classification III-IV, appendix G, or LVEF < 45%)
*Severe pulmonary dysfunction (vital capacity or diffusion capacity < 50% of predicted value) unless clearly related to NHL involvement
*Hepatic dysfunction, bilirubin or transaminase >= 2.5 x upper normal limit, unless related to lymphoma.
*Renal dysfunction (serum creatinine >=150 umol/l or clearance <= 60 ml/min)
*Prior cranial radiotherapy
*Active uncontrolled infection
*Known HIV-positivity
*(EBV) post-transplant lymphoproliferative disorder
*Documented CNS involvement during 1st line therapy (MTX intrathecal profylaxis during 1st line therapy is no exclusion criterium)
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 | EUCTR2006-002141-37-NL |
| CCMO | NL12977.078.06 |