BridgeMD
HOVON 165 CLL: A prospective randomized phase I/II trial of venetoclax treatment (26 cycles) with 6 cycles or 12 cycles of epcoritamab in patients with relapsed or refractory chronic lymphocytic leukemia or Small Lymphocytic Lymphoma. AETHER study (ABT199 + Epcoritamab THErapy for Relapsed/refractory CLL/SLL)
EU CTIS ID: 2022-500305-40-00
What this study is testing
Phase I: To determine the recommended phase II dose level (RP2D) of epcoritamab when used in combination with venetoclax for the phase II part of the trial. Phase II: To evaluate efficacy of venetoclax treatment (26 cycles) in combination with 6 cycles or 12 cycles of epcoritamab in patients with relapsed or refractory CLL in terms of undetectable minimal residual disease <10-4 (uMRD4) in the bone marrow (BM) after treatment for the two treatment groups separately.
- Phase I and Phase II (Integrated)- Other
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 relapsed or refractory CLL or SLL (SLL in phase II part only) following at least one systemic 1st-line treatment
- Estimated Glomerular Filtration Rate (eGFR) (MDRD) or estimated creatinine clearance (CrCl) ≥ 50ml/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 controlled autoimmune hemolytic anemia);
- Prothrombin time (PT)/International normal ratio (INR) <1.5x ULN and activated partial thromboplastin time (aPTT) <1.5 x ULN; unless receiving anticoagulation;
- 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). Patients 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; Please note: For patients positive for anti-HBc or antibodies for hepatitis C, HBV-DNA or HCV_DNA PCR, respectively, has to be repeated every month until 12 months after last dose of study treatment;
- Patient is able and willing to adhere to the study visit schedule and other protocol requirements;
You likely can't join if
- Patient received treatment with anti-cancer agent as follows: a. Standard agents within 2 weeks or 5 half-lives, whichever is shorter, prior to the planned first dose of epcoritamab (excluding anti-CD20 mAbs and BTKi, which can be administered until first full dose of epcoritamab); OR b. Patient received treatment with an investigational drug, within 4 weeks or 5 half-lives, whichever is shorter, prior to the planned first dose of Venetoclax;
- 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 a CD3 × CD20 bispecific antibody or CAR T-cell therapy
- Major surgery within 28 days prior to registration
- Pregnant women and nursing mothers
See the full eligibility criteria
Who can join
- Documented relapsed or refractory CLL or SLL (SLL in phase II part only) following at least one systemic 1st-line treatment
- Estimated Glomerular Filtration Rate (eGFR) (MDRD) or estimated creatinine clearance (CrCl) ≥ 50ml/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 controlled autoimmune hemolytic anemia);
- Prothrombin time (PT)/International normal ratio (INR) <1.5x ULN and activated partial thromboplastin time (aPTT) <1.5 x ULN; unless receiving anticoagulation;
- 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). Patients 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; Please note: For patients positive for anti-HBc or antibodies for hepatitis C, HBV-DNA or HCV_DNA PCR, respectively, has to be repeated every month until 12 months after last dose of study treatment;
- Patient is able and willing to adhere to the study visit schedule and other protocol requirements;
- Patient is capable of giving informed consent;
- Written informed consent
- Requiring treatment according to IWCLL criteria
- Age at least 18 years
- ECOG/WHO performance status 0-2
- Adequate BM function defined as: - Hemoglobin >5.6 mmol/l or Hb > 9 g/dL, unless low Hb is directly attributable to CLL/SLL infiltration of the BM, proven by BM biopsy; - Absolute neutrophil count (ANC) >1.0 x 109/L (1,000/μL), unless low ANC is directly attributable to CLL/SLL infiltration of the BM, proven by BM biopsy; - Platelet count >30 x 109/L (30,000/μL), unless low platelets is directly attributable to CLL/SLL infiltration in the BM;
What rules you out
- Patient received treatment with anti-cancer agent as follows: a. Standard agents within 2 weeks or 5 half-lives, whichever is shorter, prior to the planned first dose of epcoritamab (excluding anti-CD20 mAbs and BTKi, which can be administered until first full dose of epcoritamab); OR b. Patient received treatment with an investigational drug, within 4 weeks or 5 half-lives, whichever is shorter, prior to the planned first dose of Venetoclax;
- 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 a CD3 × CD20 bispecific antibody or CAR T-cell therapy
- Major surgery within 28 days prior to registration
- Pregnant women and nursing mothers
- Fertile men or women of childbearing potential (WOCBP) unless: (1) surgically sterile or ≥ 2 years after the onset of menopause; (2) willing to use a highly effective contraceptive method such as oral contraceptives, intrauterine device or sexual abstinence during study treatment and for 4 months after last dose of epcoritamab and 30 days after last dose of venetoclax
- Previous participation in the HO139 CLL or HO140 CLL trial and eligible for and willing to participate in the HO159 CLL trial
- Current participation in other clinical trial and using study medication
- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Transformation of CLL (Richter’s transformation)
- a. Ongoing active bacterial, viral, fungal, mycobacterial, parasitic or other infection requiring systemic treatment (excluding prophylactic treatment) at the time of enrollment or within the previous 2 weeks prior to the planned first dose of trial drug, including COVID-19 infection. Note that a past COVID-19 infection may be a risk factor, but if resolved and the subject is vaccinated, it may be allowable to enroll the subject. b. Has suspected active or inadequately treated latent tuberculosis;
- Prior allogeneic stem cell transplantation and/or solid organ transplantation
- Patient with a history of confirmed progressive multifocal leukoencephalopathy (PML)
- Malignancies other than CLL/SLL 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 uncontrolled severe bleeding diathesis (e.g., hemophilia or severe von Willebrand disease)
- Patient received prior venetoclax treatment within 24 months of registration OR patient had progressed during previous venetoclax treatment
- 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
- CTCAE grade III-IV cardiovascular disease including but not limited to: - Unstable or uncontrolled disease/condition related to or affecting cardiac function, eg, unstable angina, congestive heart failure grade III or IV as classified by the New York Heart Association, uncontrolled clinically significant cardiac arrhythmia (CTCAE grade II or higher), or clinically significant electrocardiogram (ECG) abnormalities. - Myocardial infarction within 6 months prior to registration. - Subject age ≥75 and 2 or more active grade ≥2 cardiovascular conditions. - Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia’s formula (QTcF) >480 msec. NOTE: this criterion does not apply to subjects with a left bundle branch block. - Stroke or intracranial hemorrhage within 6 months prior to registration.
- Severe pulmonary dysfunction (CTCAE grade III-IV)
- Severe neurological or psychiatric disease (CTCAE grade III-IV)
- Neuropathy > CTCAE grade II
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, 18-64 years, 65+ 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.