Clinical trial NCT04793399: Safety and Efficacy Evaluation of Bosutinib Plus Atezolizumab in Newly Diagnosed Chronic Leukemia Adult Patients
Official title: Multicenter, Open-label, Phase Ib/II Trial to Evaluate Safety and Efficacy for the Combination of Bosutinib Plus Atezolizumab in Newly Diagnosed Chronic Myeloid Leukemia Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Chronic Phase-Chronic Myeloid Leukemia
Lead sponsor: Fundacion Espanola para la Curacion de la Leucemia Mieloide Cronica
Sponsor class: OTHER
Collaborators: name: Pfizer
name: Roche Farma, S.A
First posted: 2021-03-11
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female patient ≥ 18 years of age.
2. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legal representative) has been informed of all pertinent aspects of the study.
3. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
4. Newly Patient with Philadelphia chromosome positive chronic phase CML and BCR-ABL1 transcript detected at diagnosis.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
6. Adequate hepatic, renal and pancreatic function defined as:

   1. Total bilirubin within normal range or Direct bilirubin ≤ 1.5 x ULN,
   2. Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN) or ≤5 x ULN if attributable to liver involvement of leukemia,
7. Women of childbearing potential must have a negative pregnancy test documented prior enrollment. Women of childbearing potential and men must be using an adequate method of contraception.

Exclusion Criteria:

1. Pregnant or lactating women,
2. Participation in another clinical trial with any investigational drug within 30 days prior to study enrollment,
3. Any prior medical treatment for CML, including tyrosine kinase inhibitors (TKIs), with the exception of hydroxyurea,
4. Period of time since CML diagnosis longer than 6 months,
5. Hypersensitivity to the active substances or to any of the excipients of the bosutinib and/or atezolizumab formulations,
6. Major surgery or radiotherapy within 14 days of enrollment,
7. Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease,
8. Concomitant use of or need for medications known to prolong the QTc interval,
9. Concomitant use with strong CYP3A inhibitors (ketoconazole, itraconazole, clarithromycin), moderate CYP3A inhibitors (erythromycin, fluconazole, diltiazem), or strong CYP3A inducers (rifampin, carbamazepine, phenytoin),
10. History of clinically significant or uncontrolled cardiac disease, including:

    1. Stage II to IV congestive heart failure (CHF) as determined by the New York Heart Association (NYHA) classification system for heart failure.
    2. Myocardial infarction within the previous 6 months,
    3. Symptomatic cardiac arrhythmia requiring treatment,
    4. Diagnosed or suspected congenital or acquired prolonged QT history or prolonged QTc. (QTcF should not exceed 500 msec),
11. Grade III or IV fluid retention,
12. Uncontrolled hypomagnesemia or uncorrected symptomatic hypokalemia, due to potential effects on the QTc interval,
13. Uncontrolled or symptomatic hypercalcemia,
14. Recent or ongoing clinically significant gastrointestinal (GI) disorder e.g. Crohn's Disease, Ulcerative Colitis or prior total or partial gastrectomy,
15. Autoimmune or infectious active disease that require treatment,
16. CML patient not in chronic phase at diagnosis,
17. Patients with known atypical transcript. An atypical transcript is defined by the presence of any transcript in the absence of the major transcripts b3a2 (e14a2) and b2a2 (e13a2) or p210 protein,
18. Patients with known resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V). It is not necessary to perform mutation tests on the patient to be included in the study if they were not previously performed,
19. Individuals with an active malignancy,
20. Known seropositivity to human immunodeficiency virus (HIV), current acute or chronic hepatitis B (hepatitis B surface-antigen positive) and/or hepatitis C.
21. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug.
22. Patients with severe renal impairment

Primary outcomes:
measure: Safety Profile of Bosutinib 400 mg Daily in Combination With Atezolizumab in Participants With Chronic Myeloid Leukemia as First Line Treatments
timeFrame: through study completion, up to 7 months
Secondary outcomes:
measure: To Evaluate the Molecular Response (MR) Rates
timeFrame: 7 months
measure: Percentage of Participants Alive
timeFrame: 7 months
measure: Number of Confirmed MR4 and MR4.5
timeFrame: 7 months
measure: The Rate of Confirmed MR4 and MR4.5
timeFrame: 7 months
measure: Number of Complete Cytogenetic Responses (CCyR)
timeFrame: 7 months
measure: The Rate of Complete Cytogenetic Response (CCyR)
timeFrame: 7 months
measure: Days to Response (CCyR, MMR, MR4, MR4.5)
timeFrame: 7 months
measure: The Median Time to Response (CCyR, MMR, MR4, MR4.5)
timeFrame: 7 months
measure: Probability of Response (CCyR, MMR, MR4, MR4.5)
timeFrame: 7 months
measure: Number of Overall Surviving Patients
timeFrame: 7 months
measure: Number of Progression-free Survival Patients
timeFrame: 7 months
measure: Number of Failure-free Survival Patients
timeFrame: 7 months
measure: Number of Event-free Survival Patients
timeFrame: 7 months
measure: Phenotypical Assays of Cell Characterization
timeFrame: 7 months
measure: Phenotypical Assays of Differentiation, Maturation and Proliferation NK Cells Markers
timeFrame: 7 months
measure: Phenotypical Assays of CD4+ T Cells Activation Markers
timeFrame: 7 months
measure: Phenotypical Assays of Predictive Markers of CML Relapse
timeFrame: 7 months
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
Study officials:
affiliation: Hospital Ramon y Cajal
name: Valentin Garcia, Dr.
role: PRINCIPAL_INVESTIGATOR
References: