Real World Data on Ibrutinib Use in PCNSL Rel/Ref

NCT05782374 | Active Not Recruiting

• 1 other identifier: OSR REWIP
• Study Type: observational
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

PCNSL

Keywords

PCNSL; R-CHOP

Outcome Measures

Primary Outcomes (1)

• To evaluate the efficacy in terms of overall rate of responses in patients treatment

  To evaluate the efficacy in terms of overall rate of responses to treatment (ORR = sum of complete responses \[CR\] + partial responses \[PR\]) according to the IPCG 2005 criteria in a retrospective cohort of patients with relapsed / refractory PCNSL undergoing treatment with ibrutinib given as monotherapy or in combination with R-CHOP immuno-chemotherapy.

  6MONTH

Secondary Outcomes (5)

• Evaluate the effectiveness in terms of overall survival (OS);

  6MONTH

• Evaluate the effectiveness in terms of progression-free survival (PFS);

  6MONTH

• Verification of the safety of the ibrutinib monotherapy and in combination with R-CHOP

  6MONTH

• To evaluate the role of consolidation therapy with high-dose chemotherapy

  6MONTH

• Frequency of invasive fungal infections after prophylactic antifungal therapy

  6MONTH

Study Arms (1)

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).

Drug: Ibrutinib

Interventions

Ibrutinib DRUG

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

Patients diagnosed with r/r PCNSL

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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).

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

Ospedale San Raffaele

Milan, Italy, 20132, Italy

Location

Related Publications (5)

• Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021 Aug 2;23(8):1231-1251. doi: 10.1093/neuonc/noab106.

  PMID: 34185076 BACKGROUND

• Ferreri AJM, Cwynarski K, Pulczynski E, Fox CP, Schorb E, Celico C, Falautano M, Nonis A, La Rosee P, Binder M, Fabbri A, Ilariucci F, Krampera M, Roth A, Hemmaway C, Johnson PW, Linton KM, Pukrop T, Gorlov JS, Balzarotti M, Hess G, Keller U, Stilgenbauer S, Panse J, Tucci A, Orsucci L, Pisani F, Zanni M, Krause SW, Schmoll HJ, Hertenstein B, Rummel M, Smith J, Thurner L, Cabras G, Pennese E, Ponzoni M, Deckert M, Politi LS, Finke J, Ferranti A, Cozens K, Burger E, Ielmini N, Cavalli F, Zucca E, Illerhaus G; IELSG32 study investigators. Long-term efficacy, safety and neurotolerability of MATRix regimen followed by autologous transplant in primary CNS lymphoma: 7-year results of the IELSG32 randomized trial. Leukemia. 2022 Jul;36(7):1870-1878. doi: 10.1038/s41375-022-01582-5. Epub 2022 May 13.

  PMID: 35562406 BACKGROUND

• Schorb E, Fox CP, Kasenda B, Linton K, Martinez-Calle N, Calimeri T, Ninkovic S, Eyre TA, Cummin T, Smith J, Yallop D, De Marco B, Krampera M, Trefz S, Orsucci L, Fabbri A, Illerhaus G, Cwynarski K, Ferreri AJM. Induction therapy with the MATRix regimen in patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system - an international study of feasibility and efficacy in routine clinical practice. Br J Haematol. 2020 Jun;189(5):879-887. doi: 10.1111/bjh.16451. Epub 2020 Jan 29.

  PMID: 31997308 BACKGROUND

• Kaji FA, Martinez-Calle N, Bishton MJ, Figueroa R, Adlington J, O'Donoghue M, Smith S, Byrne P, Paine S, Sovani V, Auer D, James E, Bessell EM, Grainge MJ, Fox CP. Improved survival outcomes despite older age at diagnosis: an era-by-era analysis of patients with primary central nervous system lymphoma treated at a single referral centre in the United Kingdom. Br J Haematol. 2021 Nov;195(4):561-570. doi: 10.1111/bjh.17747. Epub 2021 Aug 8.

  PMID: 34368948 BACKGROUND

• Sieg N, Naendrup JH, Godel P, Balke-Want H, Simon F, Deckert M, Gillessen S, Kreissl S, Brockelmann PJ, Borchmann P, von Tresckow B, Heger JM. Treatment patterns and disease course of previously untreated Primary Central Nervous System Lymphoma: Feasibility of MTX-based regimens in clinical routine. Eur J Haematol. 2021 Aug;107(2):202-210. doi: 10.1111/ejh.13639. Epub 2021 May 26.

  PMID: 33960535 BACKGROUND

MeSH Terms

Interventions

ibrutinib

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: LYMPHOMA UNIT DIRECTOR

Study Record Dates

• First Submitted: August 24, 2022
• First Posted: March 23, 2023
• Study Start: August 10, 2022
• Primary Completion: January 10, 2023
• Study Completion (Estimated): August 10, 2026
• Last Updated: February 3, 2026

Record last verified: 2026-01

Locations

IT (1)