The following categories of HCL patients needing anti-leukemic treatment are eligible for inclusion in this protocol: 1) Patients whose disease is refractory to therapy with purine analogues (no CR no PR, or relapse ≤1 year following treatment). 2) Patients who relapse early (≥1 year and ≤2 years) after the first course of a purine analogue (pentostatin or cladribine), or who relapse whenever after a second or later course. If the first relapse is accompanied by bone marrow hypoplasia (<20% hematopoietic cells on histological analysis), which would advise against chemotherapy with a purine analogue, the patient is eligible even if the relapse occurs >2 years after the first course. 4) Patients who: i) manifested severe side effects from a previous therapy with purine analogues (including, but not limited to, prolonged and profound myelosuppression and immunosuppression, infectious complications, renal failure, vasculitis; autoimmune hemolytic anemia); or ii) are deemed by the investigator medically unfit for chemotherapy with purine analogues (for example because of old age and/or significant comorbidities); or iii) firmly refuse to undergo chemotherapy (for example because they are Jehovah's witnesses and want to avoid any chemotherapy-induced need of blood product transfusions); or iv) have an active infection which would make chemotherapy with purine analogs risky; in this case patients enrolled in, Cohort-1/Phase-B and Cohort-3) are allowed to start vemurafenib with or without cobimetinib immediately, whereas obinutuzumab should be started only after the active infection has been controlled.
Conditions
Brief summary
1. The primary endpoint in each cohort is to meet or exceed a pre-determined rate of response (complete or overall response as specified later for each cohort) according to a per-protocol analysis. The rate of response will be also calculated according to the intention-to-treat analysis for informative purpose only, because this is a phase- 2 non-randomized trial primarily designed to test the anti-leukemic activity of the study drugs.
Detailed description
1. To describe the type, incidence, grade and relationship to the study drugs of adverse events (AE) occurring in each cohort., 2. To describe separately in each cohort: the time to response; the relapse-free survival (or response duration); the treatment-free survival; the progression-free survival; the event-free survival; the disease-specific survival; the overall survival; the specific type of, and response to, other anti-leukemic treatments.
Interventions
Sponsors
Eligibility
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. The primary endpoint in each cohort is to meet or exceed a pre-determined rate of response (complete or overall response as specified later for each cohort) according to a per-protocol analysis. The rate of response will be also calculated according to the intention-to-treat analysis for informative purpose only, because this is a phase- 2 non-randomized trial primarily designed to test the anti-leukemic activity of the study drugs. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To describe the type, incidence, grade and relationship to the study drugs of adverse events (AE) occurring in each cohort., 2. To describe separately in each cohort: the time to response; the relapse-free survival (or response duration); the treatment-free survival; the progression-free survival; the event-free survival; the disease-specific survival; the overall survival; the specific type of, and response to, other anti-leukemic treatments. | — |
Countries
Italy