OptiMATe: De-escalated Induction Treatment in Primary CNS Lymphoma

NCT04931368 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: SCC215
• Study Type: interventional
• Target: 331
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary Central Nervous System Lymphoma

Outcome Measures

Primary Outcomes (1)

• Event-free survival (EFS)

  time from randomization to premature end of treatment due to any reason, lymphoma progression or death, whichever occurs first

  up to 24 months after end of treatment

Secondary Outcomes (7)

• Overall survival (OS)

  up to 24 months after end of treatment

• Progression free survival (PFS)

  up to 24 months after end of treatment

• 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 rate after consolidation therapy

  30 days after ASCT

• rate of patients reaching consolidation therapy

  determined up to 4 weeks after response assessment II

Other Outcomes (11)

• Comparison of de-escalated regimen to standard induction therapy regarding safety

  up to 60 days after ASCT

• Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity

  up to 24 months after end of treatment

• Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity

  up to 24 months after end of treatment

Study Arms (2)

Control treatment (Arm A)

ACTIVE COMPARATOR

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

Experimental treatment (Arm B)

EXPERIMENTAL

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

Interventions

Experimental Treatment: one course Rituximab/HD-Methotrexate, two courses of MATRix DRUG

De-escalated induction treatment with R/HD-MTX and two courses of MATRix

Experimental treatment (Arm B)

Control intervention: four courses of MATRix DRUG

Patients receive four courses of MATRix as induction treatment.

Control treatment (Arm A)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Klinikum Stuttgart: lead
• German Federal Ministry of Education and Research: collaborator
• University Hospital Freiburg: collaborator

Study Sites (1)

Klinikum Stuttgart

Stuttgart, Baden-Wurttemberg, 70174, Germany

Location

Study Officials

• Gerald Illerhaus, Prof

  Klinikum Stuttgart

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2020
• First Posted: June 18, 2021
• Study Start: June 28, 2021
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: March 18, 2026

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Study protocol: 1st quarter 2021 Not before 2nd quarter 2028: Anonymised patient data
• Access Criteria: To get access to anonymised patient data, a research proposal/project plan is required.

Locations

DE (1)