Primary Central Nervous System LymphomaPhase 3BLOCAGE-01NCT02313389
Maintenance Treatment Versus Observation in Elderly Patients With PCNS Lymphoma
A Phase 3 study testing Rituximab, Methotrexate, Temozolomide in people with Primary Central Nervous System Lymphoma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Primary Central Nervous System Lymphoma
- What is being tested?
- Rituximab, Methotrexate, Temozolomide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 428 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2015to Apr 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
Hypothesis
Our hypothesis is that maintenance chemotherapy will prolong complete remission obtained after a standard induction chemotherapy with an acceptable toxicity in the elderly.
Read more
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
Read the 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
- Conditions
- Primary Central Nervous System Lymphoma
- Being tested
- Rituximab, Methotrexate, Temozolomide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab, Methotrexate, TemozolomideDrug
Seven monthly R-MT cycles including high dose MTX (3.5g/m2, D1), TMZ, rituximab.
| Study group | Role | What they receive |
|---|---|---|
| maintenance chemotherapy | Experimental | 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 Receives: Drug: Rituximab, Methotrexate, Temozolomide |
| observation | No intervention | 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression free survival
Measured: 6 years
Secondary outcomes (4)
overall survival
Measured: 6 years
Toxicity graded according to the NCI-CTCAE
Toxicity graded according to the NCI-CTCAE
Measured: 6 years
Cognitive functions evaluated by a standardized and validated test battery exploring 5 cognitive domains
Cognitive functions evaluated by a standardized and validated test battery exploring 5 cognitive domains
Measured: 6 years
Quality of life
Quality of life assessed by the EORTC QLC-C30 questionnaire and the brain cancer module (BCM20)
Measured: 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2014 (estimated)
- Study startSep 2015
- Primary completionApr 2023 (estimated)
- Study completionApr 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Central Nervous System LymphomaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 428 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Khe HOANG-XUAN, Md, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02313389
- Sponsor's protocol ID
- P130950
- Other IDs
- 2014-002597-37, 2014
- Acronym
- BLOCAGE-01
- Status last verified
- Feb 2022
- First submitted
- 5 Dec 2014
- Last updated
- 2 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Rozenblum L, Houillier C, Baptiste A, Soussain C, Edeline V, Naggara P, Soret M, Causse-Lemercier V, Willems L, Choquet S, Ursu R, Galanaud D, Belin L, Hoang-Xuan K, Kas A. Interim FDG-PET improves treatment failure prediction in primary central nervous system lymphoma: An LOC network prospective multicentric study. Neuro Oncol. 2024 Jul 5;26(7):1292-1301. doi: 10.1093/neuonc/noae029.
PubMed 38366824
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02313389
- Acronym / sponsor ID
- BLOCAGE-01 / P130950
- Conditions
- Primary Central Nervous System Lymphoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 428 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Sep 2015
- Primary completion
- Apr 2023 (estimated)
- Study completion
- Apr 2023 (estimated)
- First posted
- 10 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| maintenance chemotherapy | Experimental | Drug: Rituximab, Methotrexate, TemozolomideClinical 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 |
| observation | No intervention | –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 |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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)
Key exclusion criteria (6 listed)
- Positive HIV serology
- Preexisting immunodeficiency (organ transplant recipient)
- Prior treatment for PCNSL
- Isolated primary intra-ocular lymphoma
- Low grade lymphoma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rituximab, Methotrexate, TemozolomideSeven monthly R-MT cycles including high dose MTX (3.5g/m2, D1), TMZ, rituximab. | Drug | maintenance chemotherapy |
Primary outcome
progression free survival
Time frame: 6 years
4 secondary outcomes
overall survival
Time frame: 6 years
Toxicity graded according to the NCI-CTCAE
Time frame: 6 years
Cognitive functions evaluated by a standardized and validated test battery exploring 5 cognitive domains
Time frame: 6 years
Quality of life
Time frame: 6 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2022.
- Derived from this study: PubMed 38366824Rozenblum L, Houillier C, Baptiste A, Soussain C, Edeline V, Naggara P, Soret M, Causse-Lemercier V, Willems L, Choquet S, Ursu R, Galanaud D, Belin L, Hoang-Xuan K, Kas A. Interim FDG-PET improves treatment failure prediction in primary central nervous system lymphoma: An LOC network prospective multicentric study. Neuro Oncol. 2024 Jul 5;26(7):1292-1301. doi: 10.1093/neuonc/noae029.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Khe HOANG-XUAN, Md, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rituximab, Methotrexate, Temozolomide in people with Primary Central Nervous System Lymphoma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
progression free survival (time frame: 6 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02313389, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2022.