BLOCAGE-01: Maintenance Treatment Versus Observation in Elderly Patients With PCNS Lymphoma

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02313389

Collaborator

(none)

428

Enrollment

Location

Arms

Duration (Months)

4.7

Patients Per Site Per Month

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Primary Central Nervous System Lymphoma	Drug: Rituximab, Methotrexate, Temozolomide	Phase 3

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.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

428 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase III Trial Evaluating Maintenance Treatment Versus Observation in Elderly Patients Suffering From Primary Central Nervous System Lymphoma in Complete Remission After High Dose Methotrexate Based Chemotherapy in First Line

Study Start Date :

Sep 1, 2015

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: maintenance chemotherapy Clinical examination and MRI will be performed every 3 months for 2 years and then every 6 months until tumor progression. Neurocognitive tests will be performed at randomization and annually. Quality of life questionnaires at randomisation and every 3 months	Drug: Rituximab, Methotrexate, Temozolomide Seven monthly R-MT cycles including high dose MTX (3.5g/m2, D1), TMZ, rituximab.
No Intervention: observation Clinical examination and MRI will be performed every 3 months for 2 years and then every 6 months until tumor progression. Neurocognitive tests will be performed at randomization and annually. Quality of life questionnaires at randomisation and every 3 months

Arm

Intervention/Treatment

Experimental: maintenance chemotherapy

Clinical examination and MRI will be performed every 3 months for 2 years and then every 6 months until tumor progression. Neurocognitive tests will be performed at randomization and annually. Quality of life questionnaires at randomisation and every 3 months

Drug: Rituximab, Methotrexate, Temozolomide

Seven monthly R-MT cycles including high dose MTX (3.5g/m2, D1), TMZ, rituximab.

No Intervention: observation

Outcome Measures

Primary Outcome Measures

progression free survival [6 years]

Secondary Outcome Measures

overall survival [6 years]
Toxicity graded according to the NCI-CTCAE [6 years]
Toxicity graded according to the NCI-CTCAE
Cognitive functions evaluated by a standardized and validated test battery exploring 5 cognitive domains [6 years]
Cognitive functions evaluated by a standardized and validated test battery exploring 5 cognitive domains
Quality of life [6 years]
Quality of life assessed by the EORTC QLC-C30 questionnaire and the brain cancer module (BCM20)

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Groupe Hospitalier Pitie Salpetriere	Paris		France	75013

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

Principal Investigator: Khe HOANG-XUAN, Md, PhD, Assistance Publique - Hôpitaux de Paris

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Assistance Publique - Hôpitaux de Paris

ClinicalTrials.gov Identifier:

NCT02313389

Other Study ID Numbers:

P130950
2014-002597-37

First Posted:

Dec 10, 2014

Last Update Posted:

Mar 2, 2022

Last Verified:

Feb 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 2, 2022