A prospective, multicenter, phase-II trial of ibrutinib plus venetoclax in physically fit patients with creatinine clearance >= 30 ml/min who have relapsed or refractory chronic lymphocytic leukemia (RR-CLL) with or without TP53 aberrations;HOVON 141 CLL / VIsion Trial of the HOVON and Nordic CLL study groups
- Conditions
- chronic lymphocytic leukemiaCLL10024324
- Registration Number
- NL-OMON53008
- Lead Sponsor
- HOVO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 96
• Documented relapsed/refractory CLL or SLL requiring treatment according to
IWCLL criteria (no limits on previous treatment lines; CD20 and steroids are
not considered prior therapy lines)
• Age at least 18 years.
• Adequate bone marrow function , unless directly attributable to CLL
infiltration of the bone marrow, proven by bone marrow biopsy
• Creatinine clearance (CrCL) >= 30ml/min calculated according to the modified
formula of Cockcroft and Gault or directly measured with 24hr urine collection.
• Adequate liver function as indicated
• 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
dose), negative testing for hepatitis C RNA within 42 days prior to
registration.
• WHO/ECOG performance status 0-3 stage 3 only if attributable to CLL.
• Negative pregnancy test at study entry (for women of childbearing potential).
• Male and female subjects of reproductive potential must agree to use both a
highly effective method of birth control and a barrier method during the
period of therapy and for 90 days after the last dose of study drug.
• Ability and willingness to provide written informed consent and to adhere to
the study visit schedule and other protocol requirements.
• Written informed consent.
• Any prior therapy with ibrutinib and/or venetoclax.
• Transformation of CLL (Richter*s transformation).
• Patients with a history of confirmed progressive multifocal
leukoencephalopathy (PML).
• Malignancies other than CLL currently requiring systemic therapies or not
being treated in curative intention before or showing signs of progression
after curative treatment.
• Known allergy to xanthine oxidase inhibitors and/or rasburicase if no other
appropriate prevention of tumorlysis is considered feasible by the treating
physician.
• Known bleeding disorders (e.g., von Willebrand*s disease or hemophilia).
• Uncontrolled or active infection.
• Patients requiring treatment with a strong cytochrome P450 (CYP) 3A
inhibitor or anticoagulant therapy with warfarin or phenoprocoumon or other
vitamin K antagonists.
Please note: Patients being treated with NOACs 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
registration.
• Major surgery within 28 days prior to registration.
• Use of investigational agents which might interfere with the study drug
within 28 days prior to registration.
• Vaccination with live vaccines within 28 days prior to registration
• Steroid therapy within 7 days prior to registration, with the exception of
inhaled steroids for asthma, topical steroids, steroids up to 25 mg of
prednisolone daily to control autoimmune phenomenon*s, or replacement/stress
corticosteroids.
• Pregnant women and nursing mothers.
• 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>Primary endpoints: (Only considered for arm B of the study)<br /><br>- Proportion of patients fulfilling the criteria for progression free survival<br /><br>(PFS) at 12 months after stopping therapy (27 months after starting treatment)<br /><br>for patients randomized to stop treatment (arm B of the study), reinitiated<br /><br>treatment due to MRD positivity not considered progression </p><br>
- Secondary Outcome Measures
Name Time Method