Comparison of a fixed-duration treatment of acalabrutinib, venetoclax and obinutuzumab to a treatment of venetoclax and obinutuzumab in patients with high risk chronic lymphocytic leukemia
- Conditions
- Patients with previously untreated chronic lymphocytic leukemia with treatment requiring disease and at least one out of three risk factors (17p-deletion, TP53 mutation or Complex karyotype).Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004360-26-DE
- Lead Sponsor
- German CLL Study Group (University of Cologne)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 178
1.Documented CLL/SLL requiring treatment according to iwCLL criteria1.
2.Age at least 18 years.
3.At least one of the following risk factors: 17p- deletion, TP53 mutation, complex karyo-type (defined as defined as the presence of 3 or more chromosomal aberrations in 2 or more metaphases.
4.Life expectancy = 6 months.
5.Eastern Cooperative Oncology Group (ECOG) performance status of 0 -2.
6.Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements.
7.Adequate bone marrow function indicated by a platelet count >30 x10^9/l (unless directly attributable to CLL infiltration of the bone marrow, proven by bone marrow biopsy).
8.GFR >30 ml/min directly measured with 24hr urine collection, calculated according to the modified formula of Cockcroft and Gault (for men: GFR ˜ ((140 - age) x bodyweight) / (72 x creatinine), for women x 0, 85) or an equally accurate method.
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.
9.Adequate liver function as indicated by a total bilirubin = 2 x, AST/ALT = 2.5 x the institu-tional ULN value, unless directly attributable to the patient’s CLL or to Gilbert’s Syndrome.
10.Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative; pa-tients 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), negative testing for hepatitis C RNA within 6 weeks prior to registration.
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 650
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 650
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‘s transformation).
3.Known central nervous system involvement.
4.An individual organ/system impairment score of 4 as assessed by the CIRS definition lim-iting the ability to receive the treatment regimen of this trial with the exception of eyes, ears, nose, throat organ system (note that symptoms related to CLL should not be in-cluded in the patient’s screening CIRS score). Investigators should consult the General Rules for Severity Rating as well as the Organ-Specific Categories when assigning scores for certain conditions (i.e., pulmonary embolism) and consider the level of morbid-ity associated with a patient’s condition.
5.Decompensated hemolysis, defined as ongoing hemoglobin drop in spite of prednisolone or intravenous immunoglobulins (IVIG) being administered for hemolysis.
Prior treatment with rituximab also for other indications than CLL is not permitted.
6.Patients with a history of confirmed progressive multifocal leukoencephalopathy.
7.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 treat-ment.
8.Patients with active infections requiring IV treatment (Grade 3 or 4) within the last 2 months prior to enrollment
9.Patients with known infection with human immunodeficiency virus (HIV).
10.Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/inducers.
11.Anticoagulant therapy with warfarin or phenoprocoumon,
(alternative anticoagulation is allowed (e.g. DOACs), but patients must be properly in-formed about the potential risk of bleeding under treatment with acalabrutinib).
12.Requirement of treatment with a PPI (proton pump inhibitor). If treatment with an acid re-ducing agent is required, consider using an antacid (e.g., calcium carbonate) or an H2-receptor antagonist (e.g. ranitidine or famotidine) instead
13.History of stroke or intracranial hemorrhage within 6 months prior to registration.
14.Use of investigational agents which might interfere with the study drug within 28 days prior to registration.
15.Vaccination with live vaccines 28 days prior to registration.
16.Major surgery less than 30 days before start of treatment.
17.History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, known sensitivity or allergy to murine products.
18.Known hypersensitivity to any active substance or to any of the excipients of one of the drugs used in the trial.
19.Pregnant women and nursing mothers (a negative pregnancy test is required for all wom-en of childbearing potential within 7 days before start of treatment; further pregnancy test-ing will be performed regularly).
20.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 con-traceptive method (Pearl Index <1) and one additional effective (barrier) method dur-ing study treatment and for 18 months after the end of study treatment.
21.Inability to swallow a large number of tablets
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method