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OptiMATe: De-escalated Induction Treatment in Primary CNS Lymphoma

Phase 3
Recruiting
Conditions
Primary Central Nervous System Lymphoma
Registration Number
NCT04931368
Lead Sponsor
Klinikum Stuttgart
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
326
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
Remission rate after consolidation therapy30 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

Overall survival (OS)up to 24 months after end of treatment

time from randomization to death of any course

Remission rate prior to consolidation therapyassesed 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

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

Progression free survival (PFS)up to 24 months after end of treatment

time from randomization until disease progression, relapse or death from any cause

rate of patients reaching consolidation therapydetermined 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), QLQ-BN20up 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

Trial Locations

Locations (1)

Klinikum Stuttgart

🇩🇪

Stuttgart, Baden-Württemberg, Germany

Klinikum Stuttgart
🇩🇪Stuttgart, Baden-Württemberg, Germany
Illerhaus Gerald, Prof.
Contact

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