A prospective, open-label, multicenter randomized phase-II trial to evaluate the efficacy and safety of a sequential regimen of Gazyvaro (obinutuzumab) followed by obinutuzumab and venetoclax, followed by either standard venetoclax maintenance or MRD guided venetoclax maintenance in first-line patients with CLL and unfit for FCR-like regimens. (GIVE trial)
- Conditions
- 10024324Chronic Lymphocytic LeukemiaCLL
- Registration Number
- NL-OMON54803
- Lead Sponsor
- HOVO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 70
- Diagnosis of symptomatic CLL (according to IWCLL guidelines);
- Patients without prior treatment for CLL (Corticoid treatment administered
due to necessary immediate intervention is allowed; within the last 10 days
before start of study treatment only dose equivalents of max 20 mg prednisolone
are permitted);
- Patients aged >= 18 years, not fit for FCR-like regimens;
- Able to adhere to the study visit schedule and other protocol requirements;
- WHO performance status of <= 2;
- Laboratory test results within these ranges:
- absolute neutrophil count >= 1.0 x 109/l and platelet count >= 50 x 109/l
unless due to bone marrow infiltration,
- creatinine clearance >= 45 ml/min,
- total bilirubin 1,5 x ULN unless considered due to Gilbert*s syndrome,
- transaminases <= 3 x ULN;
-Negative serum or urine pregnancy test within 28 days prior to registration
(all females of childbearing potential) ;
- Written informed consent
- Patient is capable of giving informed consent
- Current inclusion in other clinical trials
- Intolerance of exogenous protein administration;
- History of severe allergic or anaphylactic reactions to humanized or murine
monoclonal antibodies. Known sensitivity or allergy to murine products
- Positive hepatitis serology (serology testing required at screening), as
follows:
- Hepatitis B virus (HBV): Patients with positive serology for hepatitis B
defined as positivity for
hepatitis B surface antigen (HBsAg) or hepatitis B core antibody
(anti-HBc).
- Hepatitis C virus (HCV): Patients with positive hepatitis C serology
unless HCV- (RNA) is
confirmed negative.
- HIV positive patients;
- • Active fungal, bacterial, and/or viral infection that requires systemic
therapy;
- Vaccination with a live vaccine a minimum of 28 days prior to registration.
- Use of any other experimental drug or therapy within 28 days of baseline;
- Concurrent use of other anti-cancer agents or treatments;
- History of prior malignancy, except for conditions as listed below if
patients have recovered from the acute side effects incurred as a result of
previous therapy:
- Malignancies surgically treated with curative intent and with no known
active disease present for 3 years before randomization
- Adequately treated non-melanoma skin cancer or lentigo maligna without
evidence of disease
- Adequately treated cervical carcinoma in situ without evidence of disease
- Severe cardiovascular disease (arrhythmias requiring chronic treatment,
congestive heart failure or symptomatic ischemic heart disease) (CTCAE grade
III-IV);
- Severe pulmonary dysfunction (CTCAE grade III-IV);
- Severe neurological or psychiatric disease (CTCAE grade III-IV);
- Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled
diabetes, hypertension, hyperthyroidism or hypothyroidism , etc.)
- Women who are pregnant or lactating
- Fertile men or women of childbearing potential unless: (1). surgically
sterile or >= 2 years after the onset of menopause (2). willing to use a highly
effective contraceptive method (Pearl Index <1) during study treatment and in
female patients for 18 months after end of antibody treatment and male patients
for 6 months after end of treatment.
- Any psychological, familial, sociological and geographical condition
potentially hampering compliance with the study protocol and follow-up
schedule.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• MRD negative bone marrow after maximum 24 cycles of (planned) venetoclax and<br /><br>no progression according to IWCLL criteria at any earlier timepoint.</p><br>
- Secondary Outcome Measures
Name Time Method <p>• Efficacy as assessed by additional outcome measures, including overall<br /><br>response, PFS, EFS and OS;<br /><br>• MRD in blood<br /><br>• Toxicity of venetoclax after pre-induction, especially tumorlysis and<br /><br>neutropenia<br /><br>• Quality of life<br /><br>• Geriatric assessment<br /><br>• P16 expression in skin biopsy<br /><br>• Predictive factors for response and resistance mechanisms:<br /><br>- NGS at baseline and at progression<br /><br>- Flow-based subset analysis on expression levels of Bcl-2 proteins at<br /><br>baseline, during therapy and at progression<br /><br>- Analyses of malignant and non-malignant immune cells in PB and in LN at<br /><br>baseline and during treatment </p><br>