The combination of bosutinib plus atezolizumab in first line treatment in newly diagnosis chronic-phase Chronic Myeloid Leukemia (CML) patients could potentially increase molecular responses and therefore treatment discontinuation probabilities in these patients. We propose an Open-Label Phase Ib/II Study of Bosutinib in Combination with Atezolizumab for the Treatment of New Diagnosis Chronic Phase-Chronic Myeloid Leukemia Patients.
The combination of bosutinib and atezolizumab in first line treatment in newly diagnosis chronic-phase Chronic Myeloid Leukemia (CML) patients could potentially increase molecular responses and consequently treatment discontinuation probabilities in these patients. We would like to propose an Open-Label Phase Ib/II Study of Bosutinib in Combination with Atezolizumab for the Treatment of New Diagnosis Chronic Phase-Chronic Myeloid Leukemia Patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
One cycle (28 days) only with bosutinib 400 mg/day therapy at the beginning of the trial + 12 cycles with bosutinib 400 mg/day therapy after combined therapy
12 cycles with bosutinib 400 mg/day plus atezolizumab 1680 mg q4w therapy between the monotherapy bosutinib cycles
Hospital Universitario Ramón y Cajal
Madrid, Spain
Hospital Universitario La Paz
Madrid, Spain
Safety Profile of Bosutinib 400 mg Daily in Combination With Atezolizumab in Participants With Chronic Myeloid Leukemia as First Line Treatments
All Adverse Events, despite their severity or causal relationship with the study medication, will be reported, graded according CTCAE v5.0 and analyzed.
Time frame: through study completion, up to 7 months
To Evaluate the Molecular Response (MR) Rates
Ratio of patients that reach a Molecular response
Time frame: 7 months
Percentage of Participants Alive
Percentage of patients that remain alive at different time-points over the total number or patients
Time frame: 7 months
Number of Confirmed MR4 and MR4.5
Total number of patients that reach Molecular response 4 (MR4) and Molecular Response 4.5 (MR4.5)
Time frame: 7 months
The Rate of Confirmed MR4 and MR4.5
Ratio of patients that reach MR4 and MR4.5
Time frame: 7 months
Number of Complete Cytogenetic Responses (CCyR)
Number of patients that reach a Complete Cytogenetic Responses (CCyR)
Time frame: 7 months
The Rate of Complete Cytogenetic Response (CCyR)
Ratio of patients that reach a Complete Cytogenetic Responses (CCyR)
Time frame: 7 months
Days to Response (CCyR, MMR, MR4, MR4.5)
Number of days lasted since the beginning of the treatment upt to reach molecular response.
Time frame: 7 months
The Median Time to Response (CCyR, MMR, MR4, MR4.5)
Average elapsed time measured for all included patients since the beginning of the treatment up until reach measurable cytogenetic or molecular response
Time frame: 7 months
Probability of Response (CCyR, MMR, MR4, MR4.5)
The overall estimated probability of reaching complete cytogenetic response or molecular response MMR, MR4 or MR4.5
Time frame: 7 months
Number of Overall Surviving Patients
Number of the overall surviving patients
Time frame: 7 months
Number of Progression-free Survival Patients
The following events are considered disease progression: * Acelerated Phase. * Blast Crisis. * CML-related death.
Time frame: 7 months
Number of Failure-free Survival Patients
Number of the failure-free survival patients
Time frame: 7 months
Number of Event-free Survival Patients
Number of the event-free survival patients
Time frame: 7 months
Phenotypical Assays of Cell Characterization
Phenotypical assays of the cell characterization
Time frame: 7 months
Phenotypical Assays of Differentiation, Maturation and Proliferation NK Cells Markers
Phenotypical assays of the differentiation, maturation and proliferation NK cells markers
Time frame: 7 months
Phenotypical Assays of CD4+ T Cells Activation Markers
Phenotypical assays of the CD4+ T cells activation markers
Time frame: 7 months
Phenotypical Assays of Predictive Markers of CML Relapse
Phenotypical markers assessment for relapse included 1. Cell characterization: NK cells (CD3- CD56+; CD16+ CD56+; TNFα; IFNα; Granzyme b NK-LGL cells (CD56+ CD57+), T-LGL cells (CD3+ CD57+), CD8 TCRα/β, NK markers (NKG2D, KIR2DL2/DL3/DS2, KIR2DL5B). 2. Differentiation and maturation (NKG2A/CD16) and proliferation (NK67) markers of NK cells. 3. CD4+ T cells activation markers: CD25 CD69 HLA-DR. 4. Predictive markers of CML relapse: T regs (CD4+ CD25int-hi CD127low), CD8+ T cells (PD-1/PD-L1) and plasmacytoid dendritic cells (CD86+).
Time frame: 7 months
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