Back to resultsOptiMATe: De-escalated Induction Treatment in Primary CNS Lymphoma (OptiMATe)
Primary Purpose
Primary Central Nervous System Lymphoma
Status
Recruiting
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Experimental Treatment: one course Rituximab/HD-Methotrexate, two courses of MATRix
Control intervention: four courses of MATRix
Sponsored by
About this trial
This is an interventional treatment trial for Primary Central Nervous System Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Immunocompetent patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system (PCNSL).
- Male or female patients aged 18-65 years irrespective of ECOG or 66-70 years with ECOG Performance Status ≤2.
- Histologically or cytologically assessed diagnosis of B-cell lymphoma by local pathologist. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy.
- Disease exclusively located in the CNS.
- At least one measurable lesion.
- Previously untreated patients (previous or ongoing steroid treatment admitted)
- Negative pregnancy test
- Written informed consent obtained according to international guidelines and local laws by patient or authorized legal representative in case patient is temporarily legally not competent due to his or her disease.
- Ability to understand the nature of the trial and the trial related procedures and to comply with them.
Exclusion Criteria:
- Congenital or acquired immunodeficiency including HIV infection and previous organ transplantation.
- Systemic lymphoma manifestation (outside the CNS).
- Primary vitreoretinal lymphoma without manifestation in the brain parenchyma or spinal cord
- Previous or concurrent malignancies with the exception of surgically cured carcinoma in situ of the cervix, carcinoma of the skin or other kinds of cancer without evidence of disease for at least 5 years.
- Previous Non-Hodgkin lymphoma at any time.
- Inadequate renal function (clearance < 60 ml/min).
- Inadequate bone marrow, cardiac, pulmonary or hepatic function according to investigator´s decision
- Active hepatitis B or C disease.
- Concurrent treatment with other experimental drugs or participation in an interventional clinical trial with study medication being administered within the last 30 days before the start of this study.
- Third space fluid accumulation > 500 ml.
- Hypersensitivity to study treatment or any component of the formulation.
- Taking any medications that are likely to cause interactions with the study medication
- Known or persistent abuse of medication, drugs or alcohol.
- Active COVID-19-infection or non-compliance with the prevailing hygiene measures regarding the COVID-19 pandemic
- Patients without legal capacity who are unable to understand the nature, significance and consequences of the trial and without designated legal representative.
- Previous participation in this trial.
- Persons who are in a relationship of dependency/employment with the sponsor and/or the investigator.
- Any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Current or planned pregnancy, nursing period
- For fertile patients: Failure to use one of the following safe methods of contraception: intra-uterine device or hormonal contraception in combination with a mechanical method of contraception.
Sites / Locations
- Klinikum StuttgartRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Control treatment (Arm A)
Experimental treatment (Arm B)
Arm Description
Patients receive four courses of MATRix (Rituximab 2 x 375 mg/m2, HD-Methotrexate 3.5 g/m2, HD-Cytarabine 2 x 2 g/m2, Thiotepa 30 mg/m2; i.v.) as induction treatment. Response assessment with gadolinium-enhanced brain MRI (centrally reviewed) takes place after course two and four. Patient with at least PR proceed to 3rd course of MATRix after first response assessment and to HCT-ASCT (BCNU 400 mg/m2, Thiotepa 4 x 5 mg/kg; i.v.) after second response assessment. Collection of autologous stem cells is planed after the second course of MATRix.
As induction treatment, patients receive one course of Rituximab/HD-Methotrexate (Rituximab 375 mg/m2, HD-Methotrexate 3.5 g/m2; i.v.). In the absence of clinical signs of progression, patients proceed to two courses of MATRix (Rituximab 2 x 375 mg/m2, HD-Methotrexate 3.5 g/m2, HD-Cytarabine 2 x 2 g/m2, Thiotepa 30 mg/m2; i.v.) followed by a response assessment with gadolinium-enhanced brain MRI (centrally reviewed). Patients with at least PR will proceed to HCT-ASCT (BCNU 400 mg/m2, thiotepa 4 x 5 mg/kg; i.v.). Collection of autologous stem cells is planed after the first course of MATRix
Outcomes
Primary Outcome Measures
Event-free survival (EFS)
time from randomization to premature end of treatment due to any reason, lymphoma progression or death, whichever occurs first
Secondary Outcome Measures
Overall survival (OS)
time from randomization to death of any course
Progression free survival (PFS)
time from randomization until disease progression, relapse or death from any cause
Remission rate prior to consolidation therapy
Remission prior to consolidation therapy will be determined at RA II and will be divided in CR, uCR, PR, CD, PD according to IPCG criteria
Remission rate after consolidation therapy
Remission after consolidation therapy will be determined on day 30 after ASCT and will be divided in CR, uCR, PR, SD, PD according to IPCG criteria
rate of patients reaching consolidation therapy
defined as obtaining at least the first dose of consolidation therapy, will be determined after the response assessment II (following 4 cycles of MATRix in the control arm and following 1 cycle of R/HD-MTX and 2 cycles of MATRix in the experimental arm)
Quality of life (QOL), EORTC QLQ-C30,
EORTC (European Organization for research and cancer treatment) QLQ-C30, measured during screening, at response assessment II, and with beginning of RA III every 12 months until end of follow-up
Quality of life (QOL), QLQ-BN20
EORTC (European Organization for research and cancer treatment) QLQ-BN20; measured during screening, at response assessment II, and with beginning of RA III every 12 months until end of follow-up
Full Information
NCT ID
NCT04931368
First Posted
August 25, 2020
Last Updated
February 15, 2022
Sponsor
Klinikum Stuttgart
Collaborators
German Federal Ministry of Education and Research, University Hospital Freiburg
1. Study Identification
Unique Protocol Identification Number
NCT04931368
Brief Title
OptiMATe: De-escalated Induction Treatment in Primary CNS Lymphoma
Acronym
OptiMATe
Official Title
Optimizing MATRix as Remission Induction in PCNSL: De-escalated Induction Treatment in Newly Diagnosed Primary CNS Lymphoma - a Randomized Phase III Trial
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 7, 2021 (Actual)
Primary Completion Date
August 2027 (Anticipated)
Study Completion Date
May 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Klinikum Stuttgart
Collaborators
German Federal Ministry of Education and Research, University Hospital Freiburg
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This phase III study investigates if a de-escalated induction treatment in newly diagnosed primary CNS lymphoma is superior to the standard MATRix protocol in terms of event free survival.
Detailed Description
This phase III study investigates if a de-escalated induction treatment in newly diagnosed primary CNS lymphoma is superior to the standard MATRix protocol in terms of event free survival. Two arms are compared, in the experimental treatment group, participants receive one course of R/HD-MTX, followed by two courses of MATRix and autologous stem cell transplantation. In the control treatment, participants receive four coourses of MATRix followed by autologous stem cell transplantation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Central Nervous System Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
326 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control treatment (Arm A)
Arm Type
Active Comparator
Arm Description
Patients receive four courses of MATRix (Rituximab 2 x 375 mg/m2, HD-Methotrexate 3.5 g/m2, HD-Cytarabine 2 x 2 g/m2, Thiotepa 30 mg/m2; i.v.) as induction treatment. Response assessment with gadolinium-enhanced brain MRI (centrally reviewed) takes place after course two and four. Patient with at least PR proceed to 3rd course of MATRix after first response assessment and to HCT-ASCT (BCNU 400 mg/m2, Thiotepa 4 x 5 mg/kg; i.v.) after second response assessment. Collection of autologous stem cells is planed after the second course of MATRix.
Arm Title
Experimental treatment (Arm B)
Arm Type
Experimental
Arm Description
As induction treatment, patients receive one course of Rituximab/HD-Methotrexate (Rituximab 375 mg/m2, HD-Methotrexate 3.5 g/m2; i.v.). In the absence of clinical signs of progression, patients proceed to two courses of MATRix (Rituximab 2 x 375 mg/m2, HD-Methotrexate 3.5 g/m2, HD-Cytarabine 2 x 2 g/m2, Thiotepa 30 mg/m2; i.v.) followed by a response assessment with gadolinium-enhanced brain MRI (centrally reviewed). Patients with at least PR will proceed to HCT-ASCT (BCNU 400 mg/m2, thiotepa 4 x 5 mg/kg; i.v.). Collection of autologous stem cells is planed after the first course of MATRix
Intervention Type
Drug
Intervention Name(s)
Experimental Treatment: one course Rituximab/HD-Methotrexate, two courses of MATRix
Intervention Description
De-escalated induction treatment with R/HD-MTX and two courses of MATRix
Intervention Type
Drug
Intervention Name(s)
Control intervention: four courses of MATRix
Intervention Description
Patients receive four courses of MATRix as induction treatment.
Primary Outcome Measure Information:
Title
Event-free survival (EFS)
Description
time from randomization to premature end of treatment due to any reason, lymphoma progression or death, whichever occurs first
Time Frame
up to 24 months after end of treatment
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
time from randomization to death of any course
Time Frame
up to 24 months after end of treatment
Title
Progression free survival (PFS)
Description
time from randomization until disease progression, relapse or death from any cause
Time Frame
up to 24 months after end of treatment
Title
Remission rate prior to consolidation therapy
Description
Remission prior to consolidation therapy will be determined at RA II and will be divided in CR, uCR, PR, CD, PD according to IPCG criteria
Time Frame
assesed at RA II (Arm B: day 18-20 of cycle 2, each cycle is 21 days. Arm A: day 18-20 of cycle 4, each cycle is 21 days)
Title
Remission rate after consolidation therapy
Description
Remission after consolidation therapy will be determined on day 30 after ASCT and will be divided in CR, uCR, PR, SD, PD according to IPCG criteria
Time Frame
30 days after ASCT
Title
rate of patients reaching consolidation therapy
Description
defined as obtaining at least the first dose of consolidation therapy, will be determined after the response assessment II (following 4 cycles of MATRix in the control arm and following 1 cycle of R/HD-MTX and 2 cycles of MATRix in the experimental arm)
Time Frame
determined up to 4 weeks after response assessment II
Title
Quality of life (QOL), EORTC QLQ-C30,
Description
EORTC (European Organization for research and cancer treatment) QLQ-C30, measured during screening, at response assessment II, and with beginning of RA III every 12 months until end of follow-up
Time Frame
up to 24 months after end of treatment
Title
Quality of life (QOL), QLQ-BN20
Description
EORTC (European Organization for research and cancer treatment) QLQ-BN20; measured during screening, at response assessment II, and with beginning of RA III every 12 months until end of follow-up
Time Frame
up to 24 months after end of treatment
Other Pre-specified Outcome Measures:
Title
Comparison of de-escalated regimen to standard induction therapy regarding safety
Description
incidence of (Serious) adverse events, laboratory parameters:WBC <2.500/µl and platelets <80.000/μl , vital signs: blood pressure (mmHg), heart rate (bpm)
Time Frame
up to 60 days after ASCT
Title
Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
Description
MoCA (Montreal Cognitive Assesment) performed at screening, EOT and every 12 months until end of follow-up
Time Frame
up to 24 months after end of treatment
Title
Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
Description
WAIS III (Wechsler Adult Intelligence scale) counting test performed at screening, EOT and every 12 months until end of follow-up
Time Frame
up to 24 months after end of treatment
Title
Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
Description
WAIS III (Wechsler Adult Intelligence scale) subtest similarities and verbal fluency test performed at screening, EOT and every 12 months until end of follow-up
Time Frame
up to 24 months after end of treatment
Title
Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
Description
Trail Making Test A and B, performed at screening, EOT and every 12 months until end of follow-up
Time Frame
up to 24 months after end of treatment
Title
Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
Description
Brief Test of Attention performed at screening, EOT and every 12 months until end of follow-up
Time Frame
up to 24 months after end of treatment
Title
Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
Description
Hopkins Verbal Learning Test performed at screening, EOT and every 12 months until end of follow-up
Time Frame
up to 24 months after end of treatment
Title
Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
Description
Grooved Pegboard Test, performed at screening, EOT and every 12 months until end of follow-up
Time Frame
up to 24 months after end of treatment
Title
Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
Description
Rey-Osterrieth-Complex-Figure-Test performed at screening, EOT and every 12 months until end of follow-up
Time Frame
up to 24 months after end of treatment
Title
Unplanned hospital admissions
Description
Defined as in-patient hospitalization from randomization until 6 months after EOT visit (excluding those for study therapy and/or assessments, placement of an indwelling catheter, social/convenience admissions, respite care, elective or pre-planned treatment/surgery)
Time Frame
up to 6 months after EOT visit
Title
Length of hospital stays
Description
Measured as number of nights in hospital from randomization and until 6 months after EOT. Hospitalization must be in relation to the disease or the administered treatment or due to toxicity
Time Frame
up to 6 months after EOT visit
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Immunocompetent patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system (PCNSL).
Male or female patients aged 18-65 years irrespective of ECOG or 66-70 years with ECOG Performance Status ≤2.
Histologically or cytologically assessed diagnosis of B-cell lymphoma by local pathologist. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy.
Disease exclusively located in the CNS.
At least one measurable lesion.
Previously untreated patients (previous or ongoing steroid treatment admitted)
Negative pregnancy test
Written informed consent obtained according to international guidelines and local laws by patient or authorized legal representative in case patient is temporarily legally not competent due to his or her disease.
Ability to understand the nature of the trial and the trial related procedures and to comply with them.
Exclusion Criteria:
Congenital or acquired immunodeficiency including HIV infection and previous organ transplantation.
Systemic lymphoma manifestation (outside the CNS).
Primary vitreoretinal lymphoma without manifestation in the brain parenchyma or spinal cord
Previous or concurrent malignancies with the exception of surgically cured carcinoma in situ of the cervix, carcinoma of the skin or other kinds of cancer without evidence of disease for at least 5 years.
Previous Non-Hodgkin lymphoma at any time.
Inadequate renal function (clearance < 60 ml/min).
Inadequate bone marrow, cardiac, pulmonary or hepatic function according to investigator´s decision
Active hepatitis B or C disease.
Concurrent treatment with other experimental drugs or participation in an interventional clinical trial with study medication being administered within the last 30 days before the start of this study.
Third space fluid accumulation > 500 ml.
Hypersensitivity to study treatment or any component of the formulation.
Taking any medications that are likely to cause interactions with the study medication
Known or persistent abuse of medication, drugs or alcohol.
Active COVID-19-infection or non-compliance with the prevailing hygiene measures regarding the COVID-19 pandemic
Patients without legal capacity who are unable to understand the nature, significance and consequences of the trial and without designated legal representative.
Previous participation in this trial.
Persons who are in a relationship of dependency/employment with the sponsor and/or the investigator.
Any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Current or planned pregnancy, nursing period
For fertile patients: Failure to use one of the following safe methods of contraception: intra-uterine device or hormonal contraception in combination with a mechanical method of contraception.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gerald Illerhaus, Prof
Phone
+4971127830400
Email
g.illerhaus@klinikum-stuttgart.de
First Name & Middle Initial & Last Name or Official Title & Degree
Elisabeth Schorb, MD
Phone
+4976127035360
Email
elisabeth.schorb@uniklinik-freiburg.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gerald Illerhaus, Prof
Organizational Affiliation
Klinikum Stuttgart
Official's Role
Principal Investigator
Facility Information:
Facility Name
Klinikum Stuttgart
City
Stuttgart
State/Province
Baden-Württemberg
ZIP/Postal Code
70174
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Illerhaus Gerald, Prof.
Phone
+49711 278-30401
Email
g.illerhaus@klinikum-stuttgart.de
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
After approval through ethics committee publication of study protocol. Anonymised patient data can be provided upon project related request.
IPD Sharing Time Frame
Study protocol: 1st quarter 2021 Not before 2nd quarter 2028: Anonymised patient data
IPD Sharing Access Criteria
To get access to anonymised patient data, a research proposal/project plan is required.
Learn more about this trial
OptiMATe: De-escalated Induction Treatment in Primary CNS Lymphoma
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