Overview
Sponsor-declared trial summary
Chronic Lymphocytic Leukemia (CLL)
To characterize the dynamics of the clonal composition in progressive CLL patients harboring TP53 mutations detected by NGS, at different time points (Baseline, Weeks 2,4, 12,24,48,72, 96 and then every year until the end of study, at disease progression)
Key facts
- Sponsor
- Ospedale San Raffaele S.r.l.
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 29 Apr 2019 → ongoing
- Decision date (initial)
- 2024-08-05
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-514823-41-00
- EudraCT number
- 2017-001099-49
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Therapy, Safety
To characterize the dynamics of the clonal composition in progressive CLL patients harboring TP53 mutations detected by NGS, at different time points (Baseline, Weeks 2,4, 12,24,48,72, 96 and then every year until the end of study, at disease progression)
Conditions and MedDRA coding
Chronic Lymphocytic Leukemia (CLL)
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- >=18 years old
- Documented diagnosis of CLL according to International workshop on CLL (IwCLL) 2008 criteria
- Previously untreated (steroid treatment previously administered to control autoimmune complications is allowed)
- Negative HBsAg and negative HBcAb or positive HBcAb and negative for HBV DNA by quantitative PCR, HCV antibody negative or, in case of HCV antibody positive, HCV RNA negative
- Progressive disease requiring treatment according to IwCLL 2008 criteria
- Cohort 2 only: Evidence of a small (<20%) subclone carrying TP53 deletion by FISH
Exclusion criteria 5
- Histologically documented transformation from CLL to aggressive lymphoma (Richter transformation)
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment
- Concomitant use of warfarin or other Vitamin K antagonists
- Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor
- Evidence of clonal TP53 mutations detected by Sanger sequencing and/or del17p in =20% of the nuclei by FISH
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- TP53 mutated subclone size at WEEK 2,4,12,24,48,72,96 and yearly thereafter compared to baseline [i.e. (TP53 mutated alleles at WEEK 2,4,12,24,48,72,96 and yearly thereafter)/(TP53 mutated alleles at baseline)]
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SCP31316411 · ATC
- Active substance
- Ibrutinib
- Substance synonyms
- 1-((3R)-3-(4-AMINO-3-(4-PHENOXYPHENYL)-1H-PYRAZOLO(3,4-D)PYRIMIDIN-1-YL)PIPERIDIN-1- YL)PROP-2-EN-1-ONE
- Route of administration
- ORAL USE
- Max daily dose
- 420 mg milligram(s)
- Max total dose
- 420 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01XE27 — IBRUTINIB
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/12/984
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Ospedale San Raffaele S.r.l.
- Sponsor organisation
- Ospedale San Raffaele S.r.l.
- Address
- Via Olgettina 60
- City
- Milan
- Postcode
- 20132
- Country
- Italy
Scientific contact point
- Organisation
- Ospedale San Raffaele S.r.l.
- Contact name
- Paolo Ghia
Public contact point
- Organisation
- Ospedale San Raffaele S.r.l.
- Contact name
- Paolo Ghia
Locations
1 EU/EEA country · 7 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruitment ended | 120 | 7 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2019-04-29 | 2019-11-25 | 2025-02-12 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 5 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol | 3.0 |
| Recruitment arrangements (for publication) | Blank document_ not required under directive | 1 |
| Subject information and informed consent form (for publication) | L1_ICF_Pre-Screening_Redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_ICF_Redacted | 6.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E1_IB | 13 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-02 | Italy | Acceptable 2024-07-29
|
2024-08-05 |