OptiMATe: De-escalated Induction Treatment in Primary CNS Lymphoma

Primary Central Nervous System Lymphoma Clinical Trial

— OptiMATe  

Official title:

Optimizing MATRix as Remission Induction in PCNSL: De-escalated Induction Treatment in Newly Diagnosed Primary CNS Lymphoma - a Randomized Phase III Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04931368
• Other study ID #: SCC215
• Status: Recruiting
• Phase: Phase 3
• Start date: June 7, 2021
• Est. completion date: May 2028

Study information

• Verified date: March 2024
• Source: Klinikum Stuttgart
• Contact: Gerald Illerhaus, Prof
• Phone: +4971127830400
• Email: g.illerhaus[@]klinikum-stuttgart.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 326
• Est. completion date: May 2028
• Est. primary completion date: August 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Primary Central Nervous System Lymphoma

Intervention

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
• Control intervention: four courses of MATRix
Patients receive four courses of MATRix as induction treatment.

Locations

Country	Name	City	State
Germany	Klinikum Stuttgart	Stuttgart	Baden-Württemberg

Sponsors (3)

Lead Sponsor	Collaborator
Klinikum Stuttgart	German Federal Ministry of Education and Research, University Hospital Freiburg

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Comparison of de-escalated regimen to standard induction therapy regarding safety	incidence of (Serious) adverse events, laboratory parameters:WBC <2.500/µl and platelets <80.000/µl , vital signs: blood pressure (mmHg), heart rate (bpm)	up to 60 days after ASCT
Other	Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity	MoCA (Montreal Cognitive Assesment) performed at screening, EOT and every 12 months until end of follow-up	up to 24 months after end of treatment
Other	Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity	WAIS III (Wechsler Adult Intelligence scale) counting test performed at screening, EOT and every 12 months until end of follow-up	up to 24 months after end of treatment
Other	Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity	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	up to 24 months after end of treatment
Other	Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity	Trail Making Test A and B, performed at screening, EOT and every 12 months until end of follow-up	up to 24 months after end of treatment
Other	Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity	Brief Test of Attention performed at screening, EOT and every 12 months until end of follow-up	up to 24 months after end of treatment
Other	Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity	Hopkins Verbal Learning Test performed at screening, EOT and every 12 months until end of follow-up	up to 24 months after end of treatment
Other	Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity	Grooved Pegboard Test, performed at screening, EOT and every 12 months until end of follow-up	up to 24 months after end of treatment
Other	Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity	Rey-Osterrieth-Complex-Figure-Test performed at screening, EOT and every 12 months until end of follow-up	up to 24 months after end of treatment
Other	Unplanned hospital admissions	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)	up to 6 months after EOT visit
Other	Length of hospital stays	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	up to 6 months after EOT visit
Primary	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	Overall survival (OS)	time from randomization to death of any course	up to 24 months after end of treatment
Secondary	Progression free survival (PFS)	time from randomization until disease progression, relapse or death from any cause	up to 24 months after end of treatment
Secondary	Remission rate prior to consolidation therapy	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	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)
Secondary	Remission rate after consolidation therapy	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	30 days after ASCT
Secondary	rate of patients reaching consolidation therapy	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)	determined up to 4 weeks after response assessment II
Secondary	Quality of life (QOL), EORTC QLQ-C30,	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	up to 24 months after end of treatment
Secondary	Quality of life (QOL), QLQ-BN20	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	up to 24 months after end of treatment