BridgeMD
Treatment of chronic lymphocytic leukaemia with venetoclax and acalabrutinib in case of return of the disease after previous treatment with venetoclax in combination with immune therapy.
EU CTIS ID: 2023-505449-18-00
What this study is testing
To evaluate efficacy of acalabrutinib/venetoclax (AV) in terms of undetectable minimal residual disease (uMRD) response in bone marrow (BM) after 26 cycles of treatment in patients with CLL previously treated with venetoclax and anti-CD20 mAb.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Documented CLL or SLL requiring treatment according to IWCLL criteria (appendix A) after at least (clinical) partial response as best response after the following initial study treatment: venetoclax-rituximab in HOVON 140/GAIA or venetoclax-obinutuzumab in HOVON 139/GIVE or HOVON 140/GAIA
- Patient is capable of giving informed consent
- Written informed consent
- WHO/ECOG performance status 0-3), stage 3 only if attributable to CLL
- Age at least 18 years
- Adequate BM function defined as: Hemoglobin >5 mmol/l or Hb > 8 g/dL, Absolute neutrophil count (ANC) >0.75 x 109/L (750/μL), unless directly attributable to CLL infiltration of the BM, proven by BM biopsy, Platelet count >30 x 109/L (30,000/μL) without transfusion and irrespective whether it is attributable to CLL infiltration in the BM
You likely can't join if
- Any prior therapy with BTK inhibitor
- 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/inducer (see appendix J) or anticoagulant therapy with warfarin or phenoprocoumon or other vitamin K antagonists
- History of stroke or intracranial hemorrhage within 6 months prior to registration
See the full eligibility criteria
Who can join
- Documented CLL or SLL requiring treatment according to IWCLL criteria (appendix A) after at least (clinical) partial response as best response after the following initial study treatment: venetoclax-rituximab in HOVON 140/GAIA or venetoclax-obinutuzumab in HOVON 139/GIVE or HOVON 140/GAIA
- Patient is capable of giving informed consent
- Written informed consent
- WHO/ECOG performance status 0-3), stage 3 only if attributable to CLL
- Age at least 18 years
- Adequate BM function defined as: Hemoglobin >5 mmol/l or Hb > 8 g/dL, Absolute neutrophil count (ANC) >0.75 x 109/L (750/μL), unless directly attributable to CLL infiltration of the BM, proven by BM biopsy, Platelet count >30 x 109/L (30,000/μL) without transfusion and irrespective whether it is attributable to CLL infiltration in the BM
- Estimated Glomerular Filtration Rate (eGFR) (MDRD) or estimated creatinine clearance (CrCl) ≥ 30ml/min (Cockcroft-Gault)
- 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 (HBV) (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 anti-HBc or hepatitis C antibody may be included if they have a negative PCR within 6 weeks before enrollment. Those who are PCR positive will be excluded
- Patient is able and willing to adhere to the study visit schedule and other protocol requirements
What rules you out
- Any prior therapy with BTK inhibitor
- 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/inducer (see appendix J) 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, myocardial infarction within 6 months) (CTCAE grade III-IV)
- Severe pulmonary dysfunction (CTCAE grade III-IV)
- Severe neurological or psychiatric disease (CTCAE grade III-IV)
- Patient who has difficulty with or are unable to swallow oral medication, or have significant gastrointestinal disease that would limit absorption of oral medication
- Vaccination with live vaccines within 28 days prior to registration
- Prior treatment with venetoclax other than first line
- Use of any other experimental drug or therapy within 28 days of 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 or 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; (2) willing to use a highly effective contraceptive method during study treatment and for 30 days after end of treatment
- Current participation in other clinical trial (other than follow up HOVON139/HOVON140)
- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Other therapy with exception of chemo-/immunotherapy which is allowed also after venetoclax first line relapse
- Transformation of CLL (Richter’s transformation)
- Patient with a history of confirmed progressive multifocal leukoencephalopathy (PML)
- Malignancies other than CLL currently requiring systemic therapy or not treated in curative intention or showing signs of progression after curative treatment
- Known allergy to xanthine oxidase inhibitors and/or rasburicase
- History of drug-specific hypersensitivity or anaphylaxis to any study drug (including active product or excipient components)
- Active bleeding or history of bleeding diathesis (e.g. hemophilia or von Willebrand disease)
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.