Age-adjusted high-dose chemotherapy followed by autologous stem cell transplantation or conventional chemotherapy with R-MP as first-line treatment in elderly primary CNS lymphoma patients – a randomized phase III trial - PRIMA-CNS

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical Center - University Of Freiburg

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

9 Aug 2023 → ongoing

Decision date (initial)

2024-08-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Federal Ministry for Education and Research in Germany

External identifiers

EU CT number

2024-512320-11-00

EudraCT number

2020-001181-10

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

Primary: To demonstrate that intensified chemotherapy followed by
consolidating high-dose chemotherapy and autologous stem-cell
transplantation (HCT-ASCT) is superior to conventional chemotherapy
with R-MP followed by maintenance in elderly patients with newly
diagnosed PCNSL in terms of progression free survival (PFS).
Secondary: To compare quality of life, remission after induction
treatment, remission after maintenance treatment (arm A) /
consolidation treatment (arm B), event free survival, overall survival and
treatment related morbidities (neurotoxicity and adverse events)
between both treatment arms.

Secondary objectives 1

1. Secondary: To compare quality of life, remission after induction treatment, remission after maintenance treatment (arm A) / consolidation treatment (arm B), event free survival, overall survival and treatment related morbidities (neurotoxicity and adverse events) between both treatment arms.

Conditions and MedDRA coding

Primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is a rare lymphoma affecting only the central nervous system compartment. PCNSL patients are typically 60 years or older and have poor prognoses. Considering the poor prognosis of this patient population, this randomised phase III trial proposal is of great clinical importance to provide patients optimal treatment.

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Immunocompetent patients with newly-diagnosed primary DLBCL of the central nervous system. 2. Age > 70 years or age 65-70 years if not eligible for more intensive treatment (e.g. OptiMATe trial). 3. Histologically or cytologically assessed diagnosis of B -cell lymphoma by local pathologist. 4. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy. 5. Disease exclusively located in the CNS. 6. At least 1 measurable lesion. 7. ECOG-Performance Status ≤2. 8. Patients possibly eligible for HCT-ASCT as judged by the treating physician. 9. 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. Additional randomization criteria: 1. Patients eligible for HCT-ASCT defined by the EBL score (at most 1 of the 3 following conditions may apply: ECOG PS > 1, Barthel Index of ADL < 20 and Lachs geriatric screening > 3), improvement of PS after prephase treatment or clinical judgement by the treating physician after discussion with the study expert team. 2. No evidence of disease progression after pre-phase treatment.

Exclusion criteria 1

1. 1. Congenital or acquired immunodeficiency including HIV infection and previous organ transplantation. 2. Systemic lymphoma manifestation (outside the CNS). 3. Primary vitreoretinal lymphoma or primary leptomeningeal lymphoma without manifestation in the brain parenchyma or spinal cord. 4. Previous or concurrent malignancies with the exception of surgically cured carcinoma in situ or other kinds of cancer without evidence of disease for at least 5 years. 5. Previous systemic Non-Hodgkin lymphoma at any time. 6. Inadequate renal function (creatinine 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 administration of study medication within the last 30 days before the start of this study. 10. Clinically relevant third space fluid accumulation according to the investigator's discretion. 11. Hypersensitivity to study treatment or any component of the formulation. 12. Taking any medications 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 and who are unable to understand the nature, significance and consequences of the study and without designated legal representative. 16. Previous participation in this trial. 17. Persons who are in a relationship of dependency/employment to the sponsor and/ or investigator. 18. Any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. 19. Fertile patients refusing to use safe contraceptive methods during the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression free survival

Secondary endpoints 1

1. • Overall survival (OS) • Event free survival (EFS; defined as time from randomization to premature end of treatment (EOT) due to any reason, lymphoma progression or death, whichever occurs first) • Remission during and after induction treatment • Remission after maintenance: 6 months after RAII • Quality of life (QoL): EORTC QLQ-C30, EORTC QLQ-BN20; measured during screening period, at RAII and premature EOT visit and thereafter every 12 months during follow-up.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical Center - University Of Freiburg

Sponsor organisation

Medical Center - University Of Freiburg

Address

Breisacher Strasse 153, Mooswald Mooswald

City

Freiburg Im Breisgau

Postcode

79110

Country

Germany

Scientific contact point

Organisation

Medical Center - University Of Freiburg

Contact name

PD Dr. med. Elisabeth Schorb

Public contact point

Organisation

Medical Center - University Of Freiburg

Contact name

ECTU

Locations

2 EU/EEA countries · 47 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 71 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications