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Trial record 14 of 47 for:    "Central Nervous System Lymphoma" | "Vitamin B Complex"

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

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ClinicalTrials.gov Identifier: NCT02313389
Recruitment Status : Recruiting
First Posted : December 10, 2014
Last Update Posted : August 20, 2019
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE December 5, 2014
First Posted Date  ICMJE December 10, 2014
Last Update Posted Date August 20, 2019
Study Start Date  ICMJE September 2015
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 9, 2014)
progression free survival [ Time Frame: 6 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02313389 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2014)
  • overall survival [ Time Frame: 6 years ]
  • Toxicity graded according to the NCI-CTCAE [ Time Frame: 6 years ]
    Toxicity graded according to the NCI-CTCAE
  • Cognitive functions evaluated by a standardized and validated test battery exploring 5 cognitive domains [ Time Frame: 6 years ]
    Cognitive functions evaluated by a standardized and validated test battery exploring 5 cognitive domains
  • Quality of life [ Time Frame: 6 years ]
    Quality of life assessed by the EORTC QLC-C30 questionnaire and the brain cancer module (BCM20)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Maintenance Treatment Versus Observation in Elderly Patients With PCNS Lymphoma
Official Title  ICMJE 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
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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Primary Central Nervous System Lymphoma
Intervention  ICMJE Drug: Rituximab, Methotrexate, Temozolomide
Seven monthly R-MT cycles including high dose MTX (3.5g/m2, D1), TMZ, rituximab.
Study Arms  ICMJE
  • 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

    Intervention: Drug: Rituximab, Methotrexate, Temozolomide
  • 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

Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 9, 2014)
295
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Khe HOANG-XUAN, MD, PhD +33 - 1.42.16.03.81 khe.hoang-xuan@psl.aphp.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02313389
Other Study ID Numbers  ICMJE P130950
2014-002597-37 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Khe HOANG-XUAN, Md, PhD Assistance Publique - Hôpitaux de Paris
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP