A phase 3 multicenter, randomized, prospective, open-label trial of standard chemoimmunotherapy (FCR/BR) versus rituximab plus venetoclax (RVe) versus obinituzumab (GA101) plus venetoclax (GVe) versus obinituzumab plus ibrutinib plus venetoclax (GIVe) in fit patients with previously untreated chronic lymphocytic leukemia (CLL) without Del (17p) or TP53 mutation.
- Conditions
- Chronic Lymphocytic LeukemiaCLL10024324
- Registration Number
- NL-OMON54622
- Lead Sponsor
- niversity of Cologne
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 185
-Documented CLL requiring treatment according to iwCLL criteria.
-Age at least 18 years.
-Life expectancy >= 6 months.
-Ability and willingness to provide written informed consent and to adhere to
the study visit
schedule and other protocol requirements.
-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).
-GFR >=70ml/min directly measured with 24hr urine collection or 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 70 ml/min may be eligible if a repeat
estimate after adequate hydration is > 70 ml/min.
-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.
-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 HBVDNA
PCR is performed every month until 12 months after the last treatment cycle),
negative
testing for hepatitis C RNA within 6 weeks prior to registration.
-Eastern Cooperative Oncology Group Performance Status (ECOG) performance
status 0-
2.
-Any prior CLL-specific therapies (except for corticoid 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).
-Transformation of CLL (Richter*s transformation).
-Decompensated hemolysis, defined as ongoing hemoglobin drop in spite of
prednisolone or intravenous immunoglobulins (IVIG). Prior treatment with
rituximab even for other indications than CLL is not permitted.
-Detected del(17p) or TP53 mutation.
-Patients with a history of confirmed PML.
-Any comorbidity or organ system impairment rated with a single CIRS
(cumulative illness rating
scale) score of 4, (excluding the eyes/ears/nose/throat/larynx organ system), a
total CIRS
score of more than 6 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).
-Urinary outflow obstruction.
-Malignancies other than CLL currently requiring systemic therapies, not being
treated in curative
intention 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.
-Uncontrolled or active infection.
-Patients with known infection with human immunodeficiency virus (HIV).
-Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/inducers.
-Anticoagulant therapy with warfarin or phenoprocoumon,(rotation to alternative
anticoagulation is allowed, but note that patients being treated with NOAKs can
be included, but must be properly informed about the potential risk of bleeding
under treatment with ibrutinib).
-History of stroke or intracranial hemorrhage within 6 months prior to
randomization.
-Use of investigational agents which might interfere with the study drug within
28 days prior to
registration.
-Vaccination with live vaccines 28 days prior to registration.
-Major surgery less than 30 days before start of treatment.
-History of severe allergic or anaphylactic reactions to humanized or murine
monoclonal antibodies,
known sensitivity or allergy to murine products.
-Known hypersensitivity to any active substance or to any of the excipients of
one of the drugs
used in the trial.
-Pregnant women and nursing mothers (a negative pregnancy test is required for
all women of
childbearing potential within 7 days before start of treatment; further
pregnancy testing will be
performed regularly).
-Fertile men or women of childbearing potential unless: surgically sterile or >=
2 years after the onset of menopause or 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.
-Legal incapacity.
-Prisoners or subjects who are institutionalized by regulatory or court order.
-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>Negativity rate of minimal residual disease (MRD) in peripheral blood<br /><br>(PB) measured by flow cytometry at month (MO) 15 for the comparison<br /><br>[GVe versus standard chemoimmunotherapy (SCIT)].<br /><br>Progression free survival (PFS) for the comparison [GIVe versus SCIT]</p><br>
- Secondary Outcome Measures
Name Time Method