Clinical trial NCT04931368: OptiMATe: De-escalated Induction Treatment in Primary CNS Lymphoma
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
Overall status: RECRUITING
Phase: PHASE3
Conditions: Primary Central Nervous System Lymphoma
Lead sponsor: Klinikum Stuttgart
Sponsor class: OTHER
Collaborators: name: German Federal Ministry of Education and Research
name: University Hospital Freiburg
First posted: 2021-06-18
Enrollment: 326
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Immunocompetent patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system (PCNSL).
2. Male or female patients aged 18-65 years irrespective of ECOG or 66-70 years with ECOG Performance Status ≤2.
3. 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.
4. Disease exclusively located in the CNS.
5. At least one measurable lesion.
6. Previously untreated patients (previous or ongoing steroid treatment admitted)
7. Negative pregnancy test
8. 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.
9. Ability to understand the nature of the trial and the trial related procedures and to comply with them.

Exclusion Criteria:

1. Congenital or acquired immunodeficiency including HIV infection and previous organ transplantation.
2. Systemic lymphoma manifestation (outside the CNS).
3. Primary vitreoretinal lymphoma without manifestation in the brain parenchyma or spinal cord
4. 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.
5. Previous Non-Hodgkin lymphoma at any time.
6. Inadequate renal function (clearance \< 60 ml/min).
7. Inadequate bone marrow, cardiac, pulmonary or hepatic function according to investigator´s decision
8. Active hepatitis B or C disease.
9. 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.
10. Third space fluid accumulation \> 500 ml.
11. Hypersensitivity to study treatment or any component of the formulation.
12. Taking any medications that are likely to cause interactions with the study medication
13. Known or persistent abuse of medication, drugs or alcohol.
14. Active COVID-19-infection or non-compliance with the prevailing hygiene measures regarding the COVID-19 pandemic
15. Patients without legal capacity who are unable to understand the nature, significance and consequences of the trial and without designated legal representative.
16. Previous participation in this trial.
17. Persons who are in a relationship of dependency/employment with the sponsor and/or the investigator.
18. Any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
19. Current or planned pregnancy, nursing period
20. 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.

Primary outcomes:
measure: Event-free survival (EFS)
timeFrame: up to 24 months after end of treatment
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: up to 24 months after end of treatment
measure: Progression free survival (PFS)
timeFrame: up to 24 months after end of treatment
measure: Remission rate prior to consolidation therapy
timeFrame: 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)
measure: Remission rate after consolidation therapy
timeFrame: 30 days after ASCT
measure: rate of patients reaching consolidation therapy
timeFrame: determined up to 4 weeks after response assessment II
measure: Quality of life (QOL), EORTC QLQ-C30,
timeFrame: up to 24 months after end of treatment
measure: Quality of life (QOL), QLQ-BN20
timeFrame: up to 24 months after end of treatment
Other outcomes:
measure: Comparison of de-escalated regimen to standard induction therapy regarding safety
timeFrame: up to 60 days after ASCT
measure: Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
timeFrame: up to 24 months after end of treatment
measure: Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
timeFrame: up to 24 months after end of treatment
measure: Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
timeFrame: up to 24 months after end of treatment
measure: Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
timeFrame: up to 24 months after end of treatment
measure: Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
timeFrame: up to 24 months after end of treatment
measure: Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
timeFrame: up to 24 months after end of treatment
measure: Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
timeFrame: up to 24 months after end of treatment
measure: Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity
timeFrame: up to 24 months after end of treatment
measure: Unplanned hospital admissions
timeFrame: up to 6 months after EOT visit
measure: Length of hospital stays
timeFrame: up to 6 months after EOT visit
Locations:
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart
state: Baden-Württemberg
Study officials:
affiliation: Klinikum Stuttgart
name: Gerald Illerhaus, Prof
role: PRINCIPAL_INVESTIGATOR
References: