Relapsed/Refractory Chronic Lymphocytic Leukemia with p53 dysfunction.
Conditions
Interventions
Trade Name: DARZALEX
Pharmaceutical Form: Concentrate for solution for injection/infusion
Trade Name: IMBRUVICA
Pharmaceutical Form: Capsule
Sponsors
FILO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Immunophenotypically confirmed diagnosis of CLL (2008 iwCLL criteria) • Progressive CLL according to iwCLL criteria • Relapsed or refractory disease (= 1 previous line of treatment) with P53 genetic alteration (17p deletion and/or TP53 mutation) • ECOG status 0-2 • Age > 18 years • Negative serum pregnancy test one week prior to treatment for premenopausal women • CIRS (Cumulative Illness Rating Scale) =6 • Life expectancy > 3 months • Possibility of follow-up • Ability to understand the protocol • Written informed consent of patient and treating physician Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: • Previous treatment with ibrutinib. • Patient refusal to perform bone marrow biopsy for evaluation point • Prior other malignancy (except for adequately treated basal cell or squamous cell skin cancer, in situ cancer, or other cancer from which the subject has been disease free for = 2 years). • Known chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) 2.5 x ULN • Total bilirubin >1.5 x ULN unless rise is due to Gilbert’s syndrome or of non- hepatic origin. • Active auto-immune haemolytic anemia • Richter’s transformation • Evidence of central nervous system (CNS) involvement • Pregnant or breastfeeding women. • Adult under law-control • Fertile male and female patients who cannot or do not wish to use an effective method of contraception, during and for 12 months after the final treatment used for the purposes of the study • No afiliate to social security
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of a treatment combining daratumumab and ibrutinib in a poor risk population of relapsed CLL patients with TP53 dysfunction. ;Secondary Objective: To determine the safety profile of daratumumab in combination with ibrutinib in CLL patients;Primary end point(s): CR rate at 12 months;Timepoint(s) of evaluation of this end point: M12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Frequency and severity of tumor lysis syndrome during and after the 2 first infusions of daratumumab • Type, frequency, severity and relationship to study treatment of adverse events. Incidence of Treatment Emergent Adverse Event (TEAE), Serious Adverse Event (SAE) and laboratory abnormalities using National Cancer Institute (NCI) common toxicity criteria (CCTAE V4) • OR rate, PR rate, PR with lymphocytosis rate • MRD assessement • PFS and OS • Duration of response • Time to next treatment • Cumulative rate of Richter’s syndrome • CD38 expression in CLL cells before treatment and on ibrutinib before daratumumab initiation • Ancillary studies ;Timepoint(s) of evaluation of this end point: until the last patient has definitively stopped study treatment | — |
Countries
France
Contacts
Public ContactAUVRAY Laetitia
FILO
Outcome results
None listed