Clinical trial conducted to evaluate the effectiveness of a combination of drugs called venetoclax and rituximab adapted to the state of minimal residual disease in patients with untreated chronic lymphocytic leukemia
EU CTIS ID: 2024-518494-34-00
What this study is testing
To demonstrate that VR treatment strategy leads to 35% of complete response (CR) or complete response with incomplete hematological recovery (CRi) according to IWCLL 2018 guidelines with undetectable (<10-4) MRD in bone marrow (as determined by flow cytometry) at the completion of therapy.
- 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
- Signed Informed Consent Form
- No active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment. Patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation
- No current use of corticosteroids. EXCEPTION: Low doses of steroids (< 10 mg of prednisone or equivalent dose of other steroid) used for treatment of non-hematologic medical condition (e.g. chronic adrenal insufficiency) is permitted
- No previous autoimmune complications (e.g. autoimmune hemolytic anemia or immune thrombocytopenia) that have developed since the initial diagnosis of CLL and have required treatment with high dose corticosteroids (e.g. equivalent of > 20 mg/day of prednisone), monoclonal antibody-based therapy, or chemotherapy. Prior use of corticosteroids for reasons other than treatment of autoimmune complications of CLL is allowed
- No major surgery within 4 weeks (28 days) of first dose of study drug or minor surgery within 3 days of first dose of study drug
- No radiation therapy ≤ 4 weeks prior to study treatment initiation
You likely can't join if
- Richter's transformation confirmed by biopsy
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study
- Patients who have received strong and moderate CYP3A inhibitors and/or CYP3A inducers within 7 days prior to the first dose of venetoclax, patients who consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of venetoclax
- Patients who require use of warfarin (due to potential drug-drug interactions that may potentially increase the exposure of warfarin). Patients may be eligible if able to be taken off warfarin and started on an alternative anticoagulant
- Patients with evidence of any of the following conditions: o New York Heart Association Functional Classification III or IV congestive heart failure o History of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to registration o Recent infection requiring systemic treatment; need to have completed anti-biotic therapy > 14 days before the first dose of study drug o Cerebral vascular accident or intracranial bleed within the last 6 months o Known active chronic hepatitis C o Positive serology for hepatitis B defined as a positive test for hepatitis B surface antigen (HBsAg); in addition, if negative for HBsAg but hepatitis B core antibody (HBcAb) positive (regardless of hepatitis B surface antibody [HBsAb] status), a hepatitis B deoxyribonucleic acid (DNA) test will be performed and, if positive the subject will be ineligible; if the hepatitis B DNA test is negative (i.e. viral load undetectable) then the individual is eligible; if a patient who is HBsAg negative, HBcAb positive, and hepatitis B DNA negative is enrolled, they should be considered for either prophylactic anti-viral therapy or careful monitoring for HBV reactivation. Patients who have protective titers of HBsAb after vaccination or prior but cured hepatitis B are eligible.
- History of other malignancy that could affect compliance with the protocol or interpretation of results o Patients with a history of curatively treated basal or squamous cell carcinoma or Stage 1 melanoma of the skin or in situ carcinoma of the cervix are eligible. o Patients with a malignancy that has been treated with surgery alone with curative intent will be included. Individuals in documented remission without treatment for (> / =) 2 years prior to enrollment may be included at the discretion of the investigator.
See the full eligibility criteria
Who can join
- Signed Informed Consent Form
- No active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment. Patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation
- No current use of corticosteroids. EXCEPTION: Low doses of steroids (< 10 mg of prednisone or equivalent dose of other steroid) used for treatment of non-hematologic medical condition (e.g. chronic adrenal insufficiency) is permitted
- No previous autoimmune complications (e.g. autoimmune hemolytic anemia or immune thrombocytopenia) that have developed since the initial diagnosis of CLL and have required treatment with high dose corticosteroids (e.g. equivalent of > 20 mg/day of prednisone), monoclonal antibody-based therapy, or chemotherapy. Prior use of corticosteroids for reasons other than treatment of autoimmune complications of CLL is allowed
- No major surgery within 4 weeks (28 days) of first dose of study drug or minor surgery within 3 days of first dose of study drug
- No radiation therapy ≤ 4 weeks prior to study treatment initiation
- Patient must be able to receive xanthine oxidase inhibitor or rasburicase for tumor lysis syndrome (TLS) prophylaxis
- Negative pregnancy test (serum βHCG) for women of childbearing potential (including pre-menopausal women who have had a tubal ligation) and for all women not meeting the definition of postmenopausal (≥ 24 months of amenorrhea), and who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy. For all other women, documentation must be present in medical history confirming that the patient is not of childbearing potential. o Female patients who are not surgically sterile or postmenopausal must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the study. o Male subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy
- Ability and willingness to comply with the requirements of the study protocol
- Patient must have diagnosis of CLL or SLL that meets published 2018 IWCLL NCI-WG criteria
- No prior treatment for CLL or SLL including chemotherapy, BTK inhibitor therapy, venetoclax, small molecule signaling inhibitor, or monoclonal antibody therapy
- Patient must have an indication for treatment according to published 2018 IWCLL NCI-WG criteria
- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2
- Adequate hematologic function independent of growth factor or transfusion support, per local laboratory reference range at screening (unless caused by underlying disease, as established by extensive bone marrow involvement or as a result of hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator) defined as follows: o Hemoglobin ≥ 9 g/dL; o Absolute neutrophil count ≥ 1.0 × 109/L; o Platelet count ≥ 50 × 109/L
- Adequate renal function, per local laboratory reference range at screening, as indicated by: o Calculated creatinine clearance ≥ 30 mL/min using 24-hour Creatinine Clearance or modified Cockcroft-Gault equation (eCCR; with the use of ideal body mass [IBM] instead of mass)
- Adequate liver function, per local laboratory reference range at screening, as indicated by: o AST and ALT ≤ 2.5 × ULN o Total bilirubin ≤ 1.5 × ULN (or ≤ 3 × ULN for patients with documented Gilbert syndrome)
What rules you out
- Richter's transformation confirmed by biopsy
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study
- Patients who have received strong and moderate CYP3A inhibitors and/or CYP3A inducers within 7 days prior to the first dose of venetoclax, patients who consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of venetoclax
- Patients who require use of warfarin (due to potential drug-drug interactions that may potentially increase the exposure of warfarin). Patients may be eligible if able to be taken off warfarin and started on an alternative anticoagulant
- Patients with evidence of any of the following conditions: o New York Heart Association Functional Classification III or IV congestive heart failure o History of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to registration o Recent infection requiring systemic treatment; need to have completed anti-biotic therapy > 14 days before the first dose of study drug o Cerebral vascular accident or intracranial bleed within the last 6 months o Known active chronic hepatitis C o Positive serology for hepatitis B defined as a positive test for hepatitis B surface antigen (HBsAg); in addition, if negative for HBsAg but hepatitis B core antibody (HBcAb) positive (regardless of hepatitis B surface antibody [HBsAb] status), a hepatitis B deoxyribonucleic acid (DNA) test will be performed and, if positive the subject will be ineligible; if the hepatitis B DNA test is negative (i.e. viral load undetectable) then the individual is eligible; if a patient who is HBsAg negative, HBcAb positive, and hepatitis B DNA negative is enrolled, they should be considered for either prophylactic anti-viral therapy or careful monitoring for HBV reactivation. Patients who have protective titers of HBsAb after vaccination or prior but cured hepatitis B are eligible.
- History of other malignancy that could affect compliance with the protocol or interpretation of results o Patients with a history of curatively treated basal or squamous cell carcinoma or Stage 1 melanoma of the skin or in situ carcinoma of the cervix are eligible. o Patients with a malignancy that has been treated with surgery alone with curative intent will be included. Individuals in documented remission without treatment for (> / =) 2 years prior to enrollment may be included at the discretion of the investigator.
- Uncontrolled active systemic infection (viral, bacterial, and fungal)
- Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) test from respiratory tract specimen (e.g. nasopharyngeal swab)
- Known positive serology for human immunodeficiency virus (HIV), due to potential drug-drug interactions between anti-retroviral medications and the study drugs
- Active hepatitis C, defined by the detectable hepatitis C ribonucleic acid (RNA) in plasma by polymerase chain reaction (PCR)
- Patient is pregnant or breast-feeding
- Malabsorption syndrome or other condition that precludes enteral route of administration
- An individual organ/system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive the treatment regimen of this trial with the exception of eyes, ears, nose, throat organ system (note that symptoms related to CLL should not be included in the patient’s screening CIRS score). Investigators should consult the General Rules for Severity Rating as well as the Organ-Specific Categories when assigning scores for certain conditions (i.e., pulmonary embolism) and consider the level of morbidity associated with a patient’s condition
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.