Real World Data on Ibrutinib Use in PCNSL Rel/Ref

NCT ID: NCT05782374

Last Updated: 2025-12-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 36 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-08-10
• Study Completion Date: 2026-08-10

Brief Summary

PCNSL is a rare and aggressive subtype of B lymphoma that has been recognized as a distinct disease entity in the latest edition of the WHO Classification of Tumors of Haematopoietic and Lymphoid Tissue and is defined as DLBCL that develops exclusively in the brain parenchyma, spinal cord, leptomeninges and eye. In patients under 70 years of age without severe comorbidities, first-line treatment with induction chemo-immunotherapy according to the MATRix scheme (Methotrexate, Cytarabine, Tiothepa, Rituximab) and subsequent consolidation with HDCT followed by ASCT achieved the best results in terms of PFS and OS. Data on patients enrolled in a randomized phase 2 study showed an OS of 70% at a median FU of 88 months. In patients> 70 years of age or with low KPS, the prognosis remains significantly lower in the younger population. Several population studies have shown a stable increase over the past 30 years in terms of PFS and OS in patients aged under 70 years, while in patients over 70 years or with KPS <70%, the survival curves are not satisfactory. in part because these patients are often referred to BSC alone, despite the benefit in PFS and OS demonstrated with HD-MTX-based treatments (≥1 g / m2) combined with oral alkylating agents or cytarabine in high doses.

Detailed Description

Historically, HDCT followed by ASCT has not been considered a feasible option for elderly patients, although recent data collected in the "real life" setting and a pilot study conducted in Germany demonstrate that maintenance of the dose intensity of HD-MTX and treatment completion with HDCT / ASCT-based consolidation are similar to those in clinical studies. However, 20 to 50% of newly diagnosed PCNSL patients do not achieve a complete response with currently available treatment regimens, highlighting the need for improved induction strategies. Furthermore, even after a complete response, patients with PCNSL may experience relapse, especially in the elderly. First-line treatment failure usually occurs (70-75% of cases) within the first two years and the prognosis of this population is extremely poor as demonstrated in a retrospective study of more than 250 patients with PCNSL R / R who reported median PFS and OS at first relapse / progression of 2.2 and 3.5 months, respectively. Similar results have also been highlighted in several prospective studies in which the PFS and OS curves are equivalent. There is currently no standard of treatment for the treatment of patients with PCNSL R/R. Data extrapolated from the long-term FU of a randomized phase 2 trial suggests that patients with relapses more than 36 months after the end of first-line methotrexate-based immuno-chemotherapy could benefit from a rechallenge with the same treatment. On the other hand, for patients refractory or with relapses within 36 months or not eligible for HD-MTX, the best therapeutic choice is represented by enrollment in a clinical trial. In the absence of this option, the therapeutic choice is based on the experience of phase 2 studies.

Conditions

PCNSL

Keywords

PCNSL; R-CHOP

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: RETROSPECTIVE

Study Groups

Patients diagnosed with r/r PCNSL

Adult patients diagnosed with relapsed or refractory PCNSL who in the period between August 2020 and May 2022 were candidates for treatment with ibrutinib alone or in combination with R-CHOP or R-CHOP like (in compassionate use, or off- label).

Ibrutinib

Intervention Type: DRUG

ibrutinib alone or in combination with R-CHOP or R-CHOP like

Interventions

Ibrutinib

ibrutinib alone or in combination with R-CHOP or R-CHOP like

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histological or cytological diagnosis of DLBCL
• Disease localized exclusively in the CNS (brain, meninges, cranial nerves, eyes and / or spinal cord) both at first diagnosis and at failure
• Progressive or recurrent disease
• Previous treatment with high-dose methotrexate-based chemotherapy ± WBRT
• Age 18 - 80 years
• ECOG performance status 0-3
• Adequate hematopoiesis (platelets> 25,000 / mm3, hemoglobin> 8 g / dL, ANC> 1,000 / mm3), renal (serum creatinine <2 times UNL and creatinine clearance ≥40 mL / min), cardiac (VEF ≥50% ) and liver function (SGOT / SGPT <3 times UNL, bilirubin and alkaline phosphatase <2 times UNL).
• Patients who have been given treatment with ibrutinib, alone or in combination with immunochemotherapy, and who have or have not received the same.

Exclusion Criteria

• Patients with concomitant extra-CNS disease at presentation or relapse
• Symptomatic coronary heart disease, cardiac arrhythmias not well controlled with drugs, or myocardial infarction within the past 6 months (New York Heart Association class III or IV heart disease)
• Any other serious medical condition that could compromise the patient's ability to adhere to treatment.
• Presence of any psychological, family, sociological or geographical condition that may hinder compliance with the study protocol and the follow-up program.
• In therapy with strong CYP3A inhibitors

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IRCCS San Raffaele

OTHER

Sponsor Role: lead

Responsible Party

Andrés José Maria Ferreri

LYMPHOMA UNIT DIRECTOR

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Ospedale San Raffaele

Milan, Italy, Italy

Countries

Italy

References

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Reference Type: BACKGROUND

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Other Identifiers

OSR REWIP

Identifier Type: -

Identifier Source: org_study_id