First line treatment with VeNEtoclaX and ibruTinib induction followed by obinutuzumab intenSificaTion Exclusively in CLL/SLL Patients not in complete remission and/or with detectable bone marrow minimal residual disease (NEXT STEP trial)
- Conditions
- chronic lymphocytic leukemiaCLL10024324
- Registration Number
- NL-OMON52647
- Lead Sponsor
- HOVO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 65
• Documented CLL or SLL requiring treatment according to IWCLL criteria33,
including minimal required markers (CD5/CD19/CD23 triple positive with light
chain restriction);
• WHO performance status 0-3, stage 3 only if attributable to CLL/SLL;
• No prior treatment for CLL/SLL; prior treatment with rituximab for another
indication is allowed
• Age at least 18 years;
• Adequate BM function defined as:
- Hb > 5 mmol/l or Hb > 8 g/dL
- Absolute neutrophil count (ANC) >= 0.75 x 109/L or 750/µL
- Platelet count >= 50 x 109/L or 50,000 /µL
Unless directly attributable to CLL/SLL infiltration of the BM, proven by BM
biopsy;
• Estimated Glomerular Filtration Rate (eGFR) (MDRD) or estimated creatinine
clearance (CrCl) >= 30ml/min (Cockcroft-Gault );
Please note: in case eGFR or CrCl is <50ml/min the patient needs to be
considered high risk for TLS
• Adequate liver function as indicated:
- Serum aspartate transaminase (ASAT) and alanine transaminase (ALAT) <= 3.0 x
upper
limit of normal (ULN)
- Bilirubin <=1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or
of nonhepatic
origin);
• Prothrombin time (PT)/International normal ratio (INR) <1.5 x ULN and
activated partial thromboplastin time (aPTT) <1.5 x ULN;
• Negative serological testing for hepatitis B virus (Hepatitis B surface
antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) negative) and
hepatitis C virus (hepatitis C antibody). Subjects who are positive for
hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody
must have a negative PCR result before enrollment. Those who are PCR positive
will be excluded;
• Ability and willingness to adhere to the study visit schedule and other
protocol requirements;
• Patient is capable of giving informed consent;
• Written informed consent.
• Transformation of CLL (Richter*s transformation);
• Malignancies other than CLL/SLL currently requiring systemic therapy or not
being treated in curative intention or showing signs of progression after
curative treatment;
• Patient with CNS involvement
• Known allergy to xanthine oxidase inhibitors and/or rasburicase;
• 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;
• Active fungal, bacterial, and/or viral infection that requires systemic
therapy;
• Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled:
infection, auto-immune hemolysis, immune thrombocytopenia, diabetes,
hypertension, hyperthyroidism or hypothyroidism etc.);
• Patient known to be HIV-positive;
• Patient requiring treatment with a strong cytochrome P450 (CYP) 3A inhibitor
or anticoagulant therapy with warfarin or phenoprocoumon or other vitamin K
antagonists;
• History of stroke or intracranial hemorrhage within 6 months prior to
registration;
• 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);
• Patient with Child Pugh C
• Severe neurological or psychiatric disease (CTCAE grade III-IV);
• Vaccination with live vaccines within 28 days prior to registration;
• Use of any other experimental drug or therapy within 28 days prior to
registration
• Major surgery within 28 days prior to registration;
• Steroid therapy within 10 days prior to registration, with the exception of
inhaled steroids for
asthma, topical steroids, steroids up to 20 mg of dose equivalents of
prednisolone daily to control autoimmune phenomenon*s, or replacement/stress
corticosteroids;
• Pregnant women and nursing mothers.;
• Fertile men or women of childbearing potential unless: (1). surgically
sterile or >= 2 years after the onset of menopause, and/or (2) willing to use a
highly effective contraceptive method during study treatment and in female
patients for 3 months after end of induction treatment and 18 months after end
of treatment with obinutuzumab and male patients for 6 months after end of
treatment ; *• Current participation in other clinical trial;
• 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>- BM uMRD CR 3 months after end of intensification with ibrutinib/obinutuzumab<br /><br>in patients who were not in CR or who had detectable MRD on combination<br /><br>ibrutinib and venetoclax</p><br>
- Secondary Outcome Measures
Name Time Method