Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT02313389 |
| Other study ID # |
P130950 |
| Secondary ID |
2014-002597-37 |
| Status |
Active, not recruiting |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
September 2015 |
| Est. completion date |
April 2023 |
Study information
| Verified date |
February 2022 |
| Source |
Assistance Publique - Hôpitaux de Paris |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Hypothesis
Our hypothesis is that maintenance chemotherapy will prolong complete remission obtained
after a standard induction chemotherapy with an acceptable toxicity in the elderly.
Rationale
- Treatment of the elderly is challenging, indeed age over 60 is associated both with a
poor prognosis and a high risk of treatment induced neurotoxicity with devastating
consequences on quality of life. Therefore it has become standard practice to treat
elderly in first line with high-dose methotrexate (MTX) based polychemotherapy alone,
avoiding whole brain radiotherapy (WBRT) or deferring it for recurrence.
- There is a clear need to improve disease control after induction chemotherapy. Since
consolidation with WBRT or intensive chemotherapy with autologous stem cell rescue are
either poorly effective and/or too toxic in the elderly population, maintenance
chemotherapy is an interesting alternative approach. Several agents, such as high-dose
MTX, temozolomide (TMZ), rituximab, with a reported activity in PCNSL and acceptable
safety profile, as single agent or combined, are good candidates for maintenance
Description:
Objectives
- The primary objective is to evaluate the benefit estimated by the PFS associated with
maintenance chemotherapy compared to observation in patients ≥ 60 years having achieved
a complete response after a high-dose MTX based induction chemotherapy
- The secondary objectives are to assess:
- Overall survival
- Safety of maintenance chemotherapy
- Neurocognitive outcome
- Quality of life of the patients
Inclusion and exclusion criteria
At registration
- Inclusion criteria
- Newly diagnosed primary cerebral lymphoma
- Age >60 years
- Pathology proven diagnosis
- Positive cytology of the CSF or vitreous
- Karnofsky Performance Status >40
- No evidence of systemic NHL (body CT scan, bone marrow biopsy)
- Adequate haematological, renal and hepatic function
- Calculated creatinine clearance > 40 ml/min
- Non inclusion criteria
- Positive HIV serology
- Preexisting immunodeficiency (organ transplant recipient)
- Prior treatment for PCNSL
- Isolated primary intra-ocular lymphoma
- Low grade lymphoma
- Any other active primary malignancy
At randomization
- Complete response on MRI after induction chemotherapy according to the IPCG criteria
- Karnofsky Performance Status >40
- Adequate haematological, renal and hepatic function
Study Design
- This study is an open label multicenter randomized phase III trial comparing maintenance
chemotherapy versus observation in complete responders to high dose MTX based induction
chemotherapy.
- Patients are registered to participate in the study at time of initial diagnosis and
study enrolment before the induction chemotherapy.
- Induction chemotherapy (R-MPVA protocol) includes 4 to 5 monthly cycles of high dose MTX
(3.5g/m2, D1 and D15), procarbazine, vincristine, rituximab followed by one cycle of
high dose cytarabine consolidation.
- Randomization to observation (arm 1) or maintenance (arm 2) will be carried out only for
patients in complete response (CR) after induction chemotherapy Arm 1: Observation Arm
2: Seven monthly R-MT cycles including high dose MTX (3.5g/m2, D1), TMZ, rituximab
Sample size, duration of the study, feasibility
- 295 patients need to be enrolled to randomize 192 patients
- Duration of the study: 6 years (accrual period= 4 years; minimal follow-up = 2 years)
26 participating expert centers from the national LOC network
The trial is supported by the neurooncology ANOCEF and the lymphoma LYSA clinical research
groups.
Ancillary study LOCALYSE:
Role of [18F]-FDG brain PET in newly diagnosed primary cerebral lymphoma, in immunocompetent
patient older than 60 years
Rationale Patients older than 60 years account for half of cases of PCNSL and have a poorer
outcome. No prognostic or predictive factors exist for survival after initial remission.
[18F]FDG-PET (Fluoro Deoxy Glucose) plays a key role in grading and therapy monitoring of
systemic diffuse large B-cell type.
LOCALYZE is an ancillary PET/MR clinical study from BLOCAGE 01. The aim is to evaluate the
usefulness of [18F]FDG-PET to monitor treatment response in PCNSL (Primary Central Nervous
System Lymphoma) older than 60 years (n=56), in complement to multiparametric MRI.
Hypothesis We assume that the development of new imaging biomarker extracted from PET imaging
and multiparametric MRI, could improve the assessment of treatment response in PCNSL.
Primary aim To evaluate the predictive value of [18F]FDG-PET assessment performed at the
end-of-treatment (high-dose methotrexate based polychemotherapy), on progression free
survival in newly diagnosed PCNSL with age ≥60 years (n=56).
Primary Outcome Measures:
Progression free survival calculated from the date of completion of the end of chemotherapy
PET
Study design
Three [18F]-FDG PET/MR will be performed in the Department of Nuclear Medicine -
Pitié-Salpêtrière Hospital:
- prior to initiation of R-MPVA chemotherapy (Rituximab Methotrexate Procarbazine
Vincristine Aracytine ) (PET#1),
- after two chemotherapy cycles (PET#2),
- at the end of the first-line chemotherapy regimens (PET#3).
Inclusion criteria (=Blocage-01) Blocage01 eligibility
Exclusion criteria
- Uncontrolled diabetes with fasting glycaemia > 200 mg/dL
- Sensitivity to active substance in [18F]-FDG
- Calculated creatinine clearance < 40 ml/min
- No contraindication to MRI
