ENSAYO CLÍNICO

Reclutando

Fase II

Leucemia linfática crónica y otros SLPC, Leucemia mieloide crónica, Linfoma, Leucemia

Diciembre, 2023

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2. Diagnosis of CLL/SLL that meets iwCLL diagnostic criteria
3. For I+V cohorts: ECOG performance status of 0-1. For ibrutinib monotherapy cohorts: ECOG performance status of 0-2
4. Active disease meeting at least 1 of the following iwCLL criteria for requiring treatment: a. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia. b. Massive (ie, 6 cm below the left costal margin) or progressive or symptomatic splenomegaly. c. Massive nodes (ie, 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy. d. Progressive lymphocytosis with an increase of 50% over a 2-month period, or LDT <6 months. e. Autoimmune complications including anemia or thrombocytopenia poorly responsive to corticosteroids. f. Symptomatic or functional extranodal involvement (eg, skin, kidney, lung, spine). g. Disease-related symptoms as defined by any of the following: i. Unintentional weight loss 10% within the previous 6 months. ii. Significant fatigue (ie, ECOG performance scale 2 or worse; cannot work or unable to perform usual activities). iii. Fevers 100.5°F or 38.0°C for 2 weeks without evidence of infection. iv. Night sweats for 1 month without evidence of infection.
15. Adequate hematologic function independent of transfusion and growth factor support for at least 7 days (except for pegylated G-CSF [pegfilgrastim] and darbepoetin, which require at least 14 days) prior to screening laboratory assessment defined as: a. ANC >750/L independent of growth factor support; b. Platelet count >50,000/L independent of transfusion support for at least 7 days prior to enrollment; c. Hemoglobin >8.0 g/dL independent of transfusion support for >7 days prior to enrollment
16. Adequate hepatic function, defined as: a. Serum AST or ALT 3.0×ULN; b. Bilirubin 1.5×ULN (unless bilirubin rise is due to congenital nonhemolytic hyperbilirubinemias or of non-hepatic origin); c. Prothrombin time/international normal ratio <1.5×ULN and activated partial thromboplastin time <1.5×ULN (unless abnormalities are unrelated to coagulopathy or bleeding disorder)
17. Adequate renal function, defined as follows (using the Cockcroft-Gault equation): a. For I+V cohorts: i. In participants aged <75 years at enrollment, CrCl 45 mL/min; ii. In participants aged 75 years at enrollment, CrCl 60 mL/min. b. For ibrutinib monotherapy cohorts, CrCl 45 mL/min

1. Medical history of: a. Other malignancies, except: i. Any malignancy that was not progressing nor requiring treatment change in the last 12 months. ii. Malignancies treated within the last 12 months and considered at very low risk for recurrence: 1. Non-muscle invasive bladder cancer (solitary Ta-PUNLMP or low grade, <3 cm, no CIS). 2. Skin cancer (non-melanoma or melanoma). 3. Non-invasive cervical cancer. 4. Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, localized breast cancer and receiving antihormonal agents. 5. Localized prostate cancer (M0, N0) with a Gleason Score 7a, treated locally only (RP/RT/focal treatment). iii. Other malignancy that is considered at minimal risk of recurrence. b. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura, such as those participants with a declining hemoglobin level or platelet count secondary to autoimmune destruction within the 4 weeks prior to first dose of study treatment, or the need for prednisone >20 mg daily (or corticosteroid equivalent) to treat or control the autoimmune disease. c. Recent infection requiring systemic treatment that is ongoing or was completed 14 days before the first dose of study treatment, or any uncontrolled active systemic infection. d. Known bleeding disorders (eg, von Willebrands disease or hemophilia). e. Stroke or intracranial hemorrhage within 6 months prior to enrollment. f. Difficult to control hypertension (defined as requiring 3 hypertensive medications) or screening systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg. For participants whose screening blood pressure exceeds a systolic blood pressure of 160 mmHg or a diastolic blood pressure of 100 mmHg, the investigator should review and manage the participant appropriately according to individual practice. The participant may be rescreened if it can be demonstrated that the blood pressure reading was a single isolated elevation or is subsequently controlled and stable. g. History of myocardial infarction, ventricular arrhythmia, unstable angina, or acute coronary syndrome within 12 months prior to enrollment (if >1 year, cardiology consultation is recommended prior to study enrollment)
2. Known or suspected Richters transformation or CNS involvement
5. Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class II, III, or IV congestive heart failure as defined by the New York Heart Association Functional Classification (see Section 10.8). For participants who in the investigators opinion are considered to have a significant cardiac risk at baseline, the investigator should consider pursuing a cardiology evaluation before screening. It is the investigators responsibility to assess the risks and benefits of subsequent study enrolment
10. Participant received prior systemic anticancer therapy (including but not limited to chemotherapy, targeted therapy, immunomodulating therapy, radiotherapy, and/or monoclonal antibody) for treatment of CLL or SLL
20. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise their wellbeing) or that could prevent, limit, or confound the protocol-specified assessments

To evaluate the efficacy of I+V and ibrutinib monotherapy regimens using a tailored treatment approach in which dosing of ibrutinib is either proactively reduced or reactively modified (per the label) in response to AEs, compared with clinical trial-based historical controls of ibrutinib monotherapy and I+V

chronic leukemia, leukemia, lymphocytic