Phase 1 Study of Ibrutinib and Immuno-Chemotherapy Using Temozolomide, Etoposide, Doxil, Dexamethasone, Ibrutinib,Rituximab (TEDDI-R) in Primary CNS Lymphoma

• Status: Recruiting
• Trial end date: 2023-06-15

Summary

BACKGROUND:

• Primary CNS lymphoma (PCNSL) is a rare subtype of diffuse large B-cell lymphoma.

• The outcome for patients with this diagnosis is significantly worse than for that of systemic DLBCL. Most treatment approaches in the past have included high dose methotrexate and radiation treatment.

• Most PCNSLs appear to be of activated B-cell (ABC) origin.

• Ibrutinib is an inhibitor of Bruton s tyrosine kinase (BTK) and effective for systemic DLBCL of ABC origin.

• We propose doing a study in which ibrutinib is combined with a novel chemotherapy platform called dose adjusted temozolomide, etoposide, doxil, dexamethasone, ibrutinib, rituximab (TEDDI-R).

OBJECTIVE:

• Identify the maximum tolerated dose (MTD) of ibrutinib or the dose that achieves adequate CSF concentrations, whichever comes first, when ibrutinib is given with TEDDI-R.

ELIGIBILITY:

• Relapsed/refractory PCNSL.

• Age greater than or equal to 18 years.

• No pregnant or breast-feeding women.

• Adequate organ function (defined in protocol).

STUDY DESIGN:

• This is a phase 1 study of 40 patients.

• The study will have two components.

1. Phase 1: MTD of ibrutinib will be identified or the dose at which ibrutinib achieves a concentration of less than or equal to 100 nM in the CSF, when given in combination with TEDDI-R immuno-chemotherapy, whichever comes first.

2. Expansion cohort: Safety and tolerability of the regimen in relapsed/refractory or previously untreated PCNSL (DLBCL type) will be assessed at the final ibrutinib dose with TEDDI-R in 10 patients. Secondary objectives will be PFS and OS.

• Phase: Phase 1

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: BB 1101; Cytarabine; Dacarbazine; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate; Etoposide; Etoposide phosphate; Isavuconazole; Liposomal doxorubicin; Rituximab; Temozolomide