A phase 3 multicentre, randomized, prospective, open-label trial of Ibrutinib monotherapy versus fixed-duration Venetoclax plus Obinutuzumab versus fixed-duration Venetoclax plus Ibrutinib in patients with previously untreated chronic lymphocytic leukaemia (CLL).
- Conditions
- Chronic Lymphatic Leukemia CLL10024324
- Registration Number
- NL-OMON52308
- Lead Sponsor
- HOVO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 110
1. Documented CLL/SLL requiring treatment according to iwCLL criteria.
2. Age at least 18 years.
3. Life expectancy >= 6 months.
4. Ability and willingness to provide written informed consent and to adhere to
the study visit schedule and other protocol requirements.
5. Adequate bone marrow function independent of growth factor or
transfusion support within 2 weeks of screening initiation as follows,unless
cytopenia is due to CLL:
a. Absolute neutrophil count >= 1.0 × 109/L
b. Platelet counts >= 30 × 109/L; in cases of thrombocytopenia clearly due to
CLL (per the discretion of the investigator), platelet count should be >= 10 ×
109/L
c. Total haemoglobin >= 8 g/dL (without transfusion support, unless anaemia is
due to CLL)
6. GFR >30ml/min directly measured with 24hr urine collection, calculated
according to the modified formula of Cockcroft and Gault or an equally
accurate method.
a. For patients with creatinine values within the normal range the calculation
of the clearance is not necessary. Dehydrated patients with an estimated
creatinine clearance less than 30 ml/min may be eligible if a repeat estimate
after adequate hydration is > 30 ml/min.
7. Adequate liver function as indicated by a total bilirubin <= 2 x, AST/ ALT <=
2.5 x the institutional ULN value, unless directly attributable to the
patient's CLL or to Gilbert's Syndrome.
8. Negative serological testing for hepatitis B (HbsAg negative and anti-HBc
negative; patients positive for anti-HBc may be included if PCR for HBV DNA is
negative and HBV-DNA PCR is performed every month until 12 months after last
treatment cycle), and for hepatitis C (anti-HCV-ab negative; in case of
positive HCV anti-body test, negative HCV-PCR is required).
9. Eastern Cooperative Oncology Group Performance Status (ECOG) performance
status 0-2.
1. Any prior CLL-specific therapies (except corticosteroid treatment
administered due to necessary immediate intervention; within the last 10 days
before start of study treatment, only dose equivalents up to 20 mg prednisolone
are permitted).
2. Transformation of CLL (Richter transformation). When Richter transformation
is suspected, PET-CT and/or biopsy should be performed to rule out
transformation.
3. Patients with a history of PML.
4. An individual organ/ system impairment score of 4 as assessed by the CIRS
definition limiting the ability to receive the study treatment or any other
life-threatening illness, medical condition or organ system dysfunction that,
in the investigator*s opinion, could compromise the patients' safety or
interfere with the absorption or metabolism of the study drugs (e.g. inability
to swallow tablets or impaired resorption in the gastrointestinal tract).
5. Malignancies other than CLL currently requiring systemic therapies, not
being treated with curative intent before (unless the malignant disease is in a
stable remission due to the discretion of the treating physician or showing
signs of progression after curative treatment.
6. Uncontrolled or active infection.
7. Patients with known infection with human immunodeficiency virus (HIV).
8. Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/ inducers
(incl. up to 7 days prior to study treatment start).
9. Anticoagulant therapy with warfarin or phenprocoumon, (alternative
anticoagulation is allowed e.g. DOACs, but patients must be properly informed
about the potential risk of bleeding under treatment with ibrutinib).
10. History of stroke or intracranial hemorrhage within 6 months prior to
registration for study screening.
11. Known bleeding disorders
12. Child B / C liver cirrhosis
13. Use of investigational agents which might interfere with the study drug
within 28 days prior to registration for study screening.
14. Vaccination with live vaccines 28 days prior to registration for study
screening.
15. Major surgery less than 30 days before start of study treatment.
16. History of severe allergic or anaphylactic reactions to humanized or murine
monoclonal antibodies, known sensitivity or allergy to murine products.
17. Known hypersensitivity to any active substance or to any of the
excipients of one of the drugs used in the trial.
18. Pregnant women and nursing mothers (a negative pregnancy test is required
for all women of childbearing potential within 7 days before start of study
treatment; further pregnancy testing will be performed monthly).
19. Fertile men or women of childbearing potential unless:
a. surgically sterile or >= 2 years after the onset of menopause
b. willing to use two methods of reliable contraception including one highly
effective contraceptive method (Pearl Index <1) and one additional effective
(barrier) method during study treatment and for 18 months after the end of
study treatment.
20. Legal incapacity.
21. Prisoners or subjects who are institutionalized by regulatory or court
order.
22. Persons who are in dependence to the sponsor or an investigator.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Progression-free survival (PFS)</p><br>
- Secondary Outcome Measures
Name Time Method