Refractory or relapsed chronic lymphocytic leukemia MedDRA version: 21.0 Level: LLT Classification code 10009310 Term: CLL System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Benlysta 200 mg Injektionslösung im Fertigpen
Benlysta 200 mg Injektionslösung in einer Fertigspritze
Product Name: Benlysta 200 mg Injektionslösung im Fertigpen
Product Code: n.a.
Pharmac
Sponsors
University Hospital Tuebingen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female =18 years of age. 2. Diagnosis of CLL/SLL established according to iwCLL criteria 3. Refractory or relapsed CLL that warrants treatment (according to modified criteria for initiation of therapy (Hallek et al., 2018)): a. Massive (ie, lower edge of spleen =6 cm below the left costal margin), progressive, or symptomatic splenomegaly, or b. Massive (ie, =10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy, or c. Progressive lymphocytosis in the absence of infection, with an increase in blood ALC=50% over a 2-month period or lymphocyte doubling time of 38.0°C for =2 weeks, or iv. Night sweats for >1 month. 4. CLL relapsing after any line of treatment that included radiotherapy, chemotherapy, immunotherapy, or small molecules. Patients who relapse after a previous therapy with venetoclax can be included in the study in case of a late relapse (i.e. >18 months after venetoclax was discontinued. 5. Discontinuation of all therapy (including radiotherapy, chemotherapy, immunotherapy, or small molecules) for the treatment of CLL =2 weeks before study treatment excluding systemic corticosteroids for symptomatic control. 6. All acute toxic effects of any prior antitumor therapy resolved to Grade =1 before treatment (with the exception of alopecia [Grade 1 or 2 permitted], neurotoxicity [Grade 1 or 2 permitted], or bone marrow parameters [any of Grade 1, 2, 3, or 4 permitted]). 7. Eastern Cooperative Oncology Group [ECOG] 30 ml/min • Neutrophile count >1.000/µl (unless directly attributable to the CLL disease) 9. Negative serological Hepatitis B and C test or negative PCR in case of positive serological test without evidence of an active infection, negative HIV test within 6 weeks prior to treatment. 10. Written informed consent of the subject 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 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1. (Suspicion of) transformation of CLL (i.e. Richter’s transformation, pro-lymphocytic leukemia) or central nervous system (CNS) involvement 2. Early relapse (i.e 40 U/ml) b. postoperative (6 weeks after bilateral ovarectomy with or without hysterectomy) c. regular and correct use of a contraceptive method with a Pearl Index < 1% per year, which will have to be continued for up to four months after the discontinuation of the study drug d. sexual abstinence e. Vasectomy of the partner 21. Male subjects who are able to father a child, except men who meet the following criteria: a. willingness to abstain from heterosexual intercourse or use a protocol-recommended method contraception from the screening visit throughout the study treatment period and for four months following the last dose of study drug b. refrain from sperm donation from screening visit throughout the study treatment period and for 90 days following the last dose of study drug. 22. Indications that the subject is unlikely to adhere to the protocol (e.g., lack of compliance)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess efficacy (MRD response) of belimumab in combination with rituximab/venetoclax in CLL compared to treatment with rituximab/venetoclax alone.;Secondary Objective: •To assess safety of belimumab and rituximab/venetoclax in patients with relapsed or refractory CLL •To evaluate overall response rate (ORR) •To evaluate progression free survival (PFS) •To evaluate overall survival (OS) To evaluate duration of response (DOR) •To assess further efficacy markers of belimumab in combination with rituximab/venetoclax in CLL compared to control •Pharmacokinetics of belimumab in CLL patients;Primary end point(s): Negativity rate of minimal residual disease (MRD) in peripheral blood (PB) measured by flow cytometry at EOI MRD negativity is defined as less than one (1) CLL-cell among 10,000 leukocytes analyzed [0.01%], i.e. < 10-4. The MRD negativity rate is defined as the proportion of patients having achieved MRD negativity. Patients without any evaluable MRD sample at end of induction treatment will be kept and labeled as ‘MRD positive (=10-4)' in the analysis.;Timepoint(s) of evaluation of this end point: BAseline (14 days before therapy start), visit 1/Day 1 in each cycle (Cycle 1-6), Maintenance Therapy: once in every 4 weeks for 24 months after c1d1 of anti-CD20 therapy; End of treatment (24 months after c1d1 of anti-CD20 therapy) and in the FU Phase (Follow-up every 3 months; +/- 7 days up to 1 year (EOS)) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety (general): • Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) through EOT • Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) through EOS • Incidence of suicidal behavior, as determined by Columbia-Suicide Severity Rating Scale (CSSRS) Anti-tumor activity: • Number and percentage of overall response rate (ORR) according to iwCLL criteria: PR, CR, and CRi at EOT, as assessed by the investigator at EOI and EOT • DOR status as time from best ORR of CR, CRi, or PR until progression • Negativity rate of MRD in PB and BM measured by flow cytometry at EOI, every 3 months during maintenance therapy and at EOS • TTNT as time from d1 to next other CLL treatment Survival: • Overall and progression free survival • Overall and progression free survival of patients with 17p deletion Immunophenotyp: • Absolute changes in number and percentage of subjects in lymphocyte subset counts (B, T, NK cells) on day28, d1 of each cycle, EOI and thereafter every 4 weeks until EOT from baseline. Pharmacokinetics: • Pharmacokinetics of belimumab as assessed as follows: o Observed belimumab concentration at c1d1 and EOI Quality of life: • Overall quality of life scores (EORTC QLQ C-30) until EOS ;Timepoint(s) of evaluation of this end point: Please refer to the protocol, Trial Schedule | — |
Countries
Germany
Contacts
Public ContactZKS Tübingen
Zentrum für klinische Studien
Outcome results
None listed