Maintenance Treatment Versus Observation in Elderly Patients With PCNS Lymphoma
Conditions
Primary CNS Lymphoma.
Conditions: official terms
Lymphoma
Study Type
Interventional
Study Phase
Phase 3
Study Design
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Rituximab, Methotrexate, Temozolomide
Type: Drug
Overall Status
Not yet recruiting
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
Detailed 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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 60 Years
Gender: Both
Criteria: Inclusion criteria At registration Inclusion criteria

- newly diagnosed primary cerebral lymphoma

- Age ≥60 years

- Pathology proven diagnosis or 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

At randomization

- Complete response on MRI after induction chemotherapy according to the IPCG criteria

- Karnofsky Performance Status ≥40

- Adequate haematological, renal and hepatic function

Exclusion 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
Location
Groupe Hospitalier Pitie Salpetriere
Paris, France
Status: Not yet recruiting
Contact: Khe HOANG-XUAN, MD, PhD - +33 - 1.42.16.03.81 - khe.hoang-xuan@psl.aphp.fr
Start Date
January 2015
Completion Date
June 2021
Sponsors
Assistance Publique - Hôpitaux de Paris
Source
Assistance Publique - Hôpitaux de Paris
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page