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
- Conditions
- Chronic lymphocytic leukemiaMedDRA version: 21.0Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-004613-14-PL
- Lead Sponsor
- POLISH ADULT LEUKEMIA GROUP
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 103
1. Signed Informed Consent Form.
2. Ability and willingness to comply with the requirements of the study protocol.
3. Patient must have diagnosis of CLL or SLL that meets published 2018 IWCLL NCI-WG criteria.
4. No prior treatment for CLL or SLL including chemotherapy, BTK inhibitor therapy, venetoclax, small molecule signaling inhibitor, or monoclonal antibody therapy.
5. Patient must have an indication for treatment according to published 2018 IWCLL NCI-WG criteria.
6. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance score of = 2.
7. 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 x 109/L
o Platelet count = 50 × 109/L
8. 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).
9. 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).
10. 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.
11. 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.
12. 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.
13. 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.
14. No radiation therapy = 4 weeks prior to study treatment initiation.
15. Patient must be able to receive xanthine oxidase inhibitor or rasburicase for tumor lysis syndrome (TLS) prophylaxis.
16. Negative pregnancy test (serum ßHCG) 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 w
1. Richter's transformation confirmed by biopsy.
2. 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.
3. Uncontrolled active systemic infection (viral, bacterial, and fungal).
4. 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).
5. Known positive serology for human immunodeficiency virus (HIV), due to potential drug-drug interactions between anti-retroviral medications and the study drugs.
6. Active hepatitis C, defined by the detectable hepatitis C ribonucleic acid (RNA) in plasma by polymerase chain reaction (PCR).
7. Patient is pregnant or breast-feeding.
8. Malabsorption syndrome or other condition that precludes enteral route of administration.
9. 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.
10. 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.
11. 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.
12. Patients 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.
13. Patients with evidence 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
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 an
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method