OptiMATe: De-escalated Induction Treatment in Primary CNS Lymphoma

Klinikum Stuttgart

Status and phase: Enrolling; Phase 3

Conditions: Primary Central Nervous System Lymphoma

Treatments: Drug: Control intervention: four courses of MATRix; Drug: Experimental Treatment: one course Rituximab/HD-Methotrexate, two courses of MATRix

Study type: Interventional

Funder types: Other

Identifiers

NCT04931368

SCC215

Details and patient eligibility

About

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.

Full 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.

Enrollment: 326 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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326 participants in 2 patient groups

Control treatment (Arm A)

Active Comparator group

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.

Treatment:

Drug: Control intervention: four courses of MATRix

Experimental treatment (Arm B)

Experimental group

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

Treatment:

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