Overview
Sponsor-declared trial summary
Previously Untreated Chronic Lymphophatic Leukaemia
Evaluate the effectiveness of the sequential combination of venetoclax, delayed rituximab and ibrutinib in terms of minimal remaining undetectable disease (uMRD, <10- 4) detected with 6-color cytofluorimetry in BM as the best response at any time during treatment up to 3 months after the completion of combined therapy
Key facts
- Sponsor
- Ospedale San Raffaele S.r.l.
- Participant type
- Patients
- Age range
- 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 21 Dec 2021 → 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
- 2024-514687-33-00
- EudraCT number
- 2020-004409-30
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Others, Safety, Efficacy
Evaluate the effectiveness of the sequential combination of venetoclax, delayed rituximab and ibrutinib in terms of minimal remaining undetectable disease (uMRD, <10- 4) detected with 6-color cytofluorimetry in BM as the best response at any time during treatment up to 3 months after the completion of combined therapy
Conditions and MedDRA coding
Previously Untreated Chronic Lymphophatic Leukaemia
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Age =18 but <65 years
- Active CLL/SLL requiring treatment according to iwCLL 2018 criteria
- No previous CLL/SLL therapy
- Appropriate medullary function: a. ANC =1.0 x 109/L; B. Plt =25 x 109/L; c. Hb =8.0 g/dl
Exclusion criteria 15
- Previous treatment for CLL/SLL
- History of other malignant malignancies, except in situ carcinoma or malignant cancers treated with curative intent
- Known story or suspected transformation of Richter
- Hypersensitivity known to one or more drugs in the study
- Inadequate kidney function: CrCl <30 ml/min
- Autoimmune hemolytic anemia or uncontrolled autoimmune platelets
- Need for warfarin or derivatives therapy
- Treatment within 7 days before the first dose of the drug in the study with one of the following: a. Steroid therapy with antineoplastic intent B. Moderate or powerful cytochrome inhibitors P450 3A (CYP3A) (see Appendix G for examples) C. Moderate or strong CYP3A inducers (see Appendix G for examples)
- Administration or consumption of any of the following within 3 days before the first dose of the drug in the study: a. Pompelmo or grapefruit products B. Seville oranges (including jam containing Seville oranges) c. Carambola
- Known history of human immunodeficiency virus (HIV) or active infection with hepatitis B virus (HBV) or hepatitis C (HCV). Subjects who are positive for HBcAb, HBsAb or the hepatitis C antibody should have a negative result of the polymerase chain reaction (PCR) prior to enlistment. Those who test positive for PCR will be excluded.
- Note hypersensitivity to one or more drugs in the study
- Known hemorrhagic disorders (e.g. von Willebrand's disease) or haemophilia
- History of stroke or intracranial bleeding in the 6 months prior to enlistment
- Major surgery within 4 weeks of first dose of the drug in the study
- Cardiovascular disease currently active and clinically significant such as uncontrolled arrhythmia or congestive heart failure of class 3 or 4 as defined by the functional classification of the New York Heart Association or a history of myocardial infarction, unstable angina
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- uMRD (<10-4) evaluated by 6-color cytofluorymetry in BM as the best response at any time during treatment up to 3 months after supplementation of combination therapy (VR or VR followed by VI)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SCP16272936 · ATC
- Active substance
- Venetoclax
- Substance synonyms
- ABT-199, GDC-0199, 4-(4-((2-(4-CHLOROPHENYL)-4,4-DIMETHYLCYCLOHEX-1-EN-1-YL)METHYL)PIPERAZIN-1-YL)-N-((3-NITRO-4-((TETRAHYDRO-2H-PYRAN-4-YLMETHYL)AMINO)PHENYL)SULFONYL)-2-(1H-PYRROLO(2,3-B)PYRIDIN-5-YLOXY)BENZAMIDE
- Route of administration
- ORAL USE
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 260190 µg microgram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01XX52 — VENETOCLAX
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- 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 · 14 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruiting | 55 | 14 |
| 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 | 2021-12-21 | 2022-09-19 |
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_2024-514687-33-00 | 2 |
| Recruitment arrangements (for publication) | Blank document_ not required under directive | 1 |
| Subject information and informed consent form (for publication) | L1_ICF | 3.0 |
| Subject information and informed consent form (for publication) | L1_ICF_Privacy_Redacted | 3 |
| 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 |