OptiMATe: De-escalated Induction Treatment in Primary CNS Lymphoma
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Control treatment (Arm A) 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. |
Drug: Control intervention: four courses of MATRix
Patients receive four courses of MATRix as induction treatment.
|
| Experimental: Experimental treatment (Arm B) 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 |
Drug: Experimental Treatment: one course Rituximab/HD-Methotrexate, two courses of MATRix
De-escalated induction treatment with R/HD-MTX and two courses of MATRix
|
Outcome Measures
Primary Outcome Measures
- Event-free survival (EFS) [up to 24 months after end of treatment]
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) [up to 24 months after end of treatment]
time from randomization to death of any course
- Progression free survival (PFS) [up to 24 months after end of treatment]
time from randomization until disease progression, relapse or death from any cause
- Remission rate prior to consolidation therapy [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)]
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 [30 days after ASCT]
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 [determined up to 4 weeks after response assessment II]
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, [up to 24 months after end of treatment]
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 [up to 24 months after end of treatment]
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
Other Outcome Measures
- Comparison of de-escalated regimen to standard induction therapy regarding safety [up to 60 days after ASCT]
incidence of (Serious) adverse events, laboratory parameters:WBC <2.500/µl and platelets <80.000/μl , vital signs: blood pressure (mmHg), heart rate (bpm)
- Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity [up to 24 months after end of treatment]
MoCA (Montreal Cognitive Assesment) performed at screening, EOT and every 12 months until end of follow-up
- Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity [up to 24 months after end of treatment]
WAIS III (Wechsler Adult Intelligence scale) counting test performed at screening, EOT and every 12 months until end of follow-up
- Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity [up to 24 months after end of treatment]
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
- Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity [up to 24 months after end of treatment]
Trail Making Test A and B, performed at screening, EOT and every 12 months until end of follow-up
- Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity [up to 24 months after end of treatment]
Brief Test of Attention performed at screening, EOT and every 12 months until end of follow-up
- Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity [up to 24 months after end of treatment]
Hopkins Verbal Learning Test performed at screening, EOT and every 12 months until end of follow-up
- Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity [up to 24 months after end of treatment]
Grooved Pegboard Test, performed at screening, EOT and every 12 months until end of follow-up
- Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity [up to 24 months after end of treatment]
Rey-Osterrieth-Complex-Figure-Test performed at screening, EOT and every 12 months until end of follow-up
- Unplanned hospital admissions [up to 6 months after EOT visit]
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)
- Length of hospital stays [up to 6 months after EOT visit]
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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Immunocompetent patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system (PCNSL).
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Male or female patients aged 18-65 years irrespective of ECOG or 66-70 years with ECOG Performance Status ≤2.
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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.
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Disease exclusively located in the CNS.
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At least one measurable lesion.
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Previously untreated patients (previous or ongoing steroid treatment admitted)
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Negative pregnancy test
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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.
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Ability to understand the nature of the trial and the trial related procedures and to comply with them.
Exclusion Criteria:
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Congenital or acquired immunodeficiency including HIV infection and previous organ transplantation.
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Systemic lymphoma manifestation (outside the CNS).
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Primary vitreoretinal lymphoma without manifestation in the brain parenchyma or spinal cord
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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.
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Previous Non-Hodgkin lymphoma at any time.
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Inadequate renal function (clearance < 60 ml/min).
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Inadequate bone marrow, cardiac, pulmonary or hepatic function according to investigator´s decision
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Active hepatitis B or C disease.
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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.
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Third space fluid accumulation > 500 ml.
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Hypersensitivity to study treatment or any component of the formulation.
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Taking any medications that are likely to cause interactions with the study medication
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Known or persistent abuse of medication, drugs or alcohol.
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Active COVID-19-infection or non-compliance with the prevailing hygiene measures regarding the COVID-19 pandemic
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Patients without legal capacity who are unable to understand the nature, significance and consequences of the trial and without designated legal representative.
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Previous participation in this trial.
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Persons who are in a relationship of dependency/employment with the sponsor and/or the investigator.
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Any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
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Current or planned pregnancy, nursing period
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Klinikum Stuttgart | Stuttgart | Baden-Württemberg | Germany | 70174 |
Sponsors and Collaborators
- Klinikum Stuttgart
- German Federal Ministry of Education and Research
- University Hospital Freiburg
Investigators
- Principal Investigator: Gerald Illerhaus, Prof, Klinikum Stuttgart
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SCC215