Safety and Efficacy Evaluation of Bosutinib Plus Atezolizumab in Newly Diagnosed Chronic Leukemia Adult Patients

NCT04793399 | Terminated Phase 1 Results

• 1 other identifier: ZEROLMC-01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

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.

Conditions

Chronic Phase-Chronic Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• 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.

  through study completion, up to 7 months

Secondary Outcomes (17)

• To Evaluate the Molecular Response (MR) Rates

  7 months

• Percentage of Participants Alive

  7 months

• Number of Confirmed MR4 and MR4.5

  7 months

• The Rate of Confirmed MR4 and MR4.5

  7 months

• Number of Complete Cytogenetic Responses (CCyR)

  7 months

Study Arms (1)

Bosutinib-Atezolizumab Combination

EXPERIMENTAL

Drugs to be administered: Bosutinib 400 milligram (mg)/day Oral Tablet \[Bosulif 100mg oral tablets\] for 1 year Atezolizumab 1680 mg/28 days \[Tecentriq 840 MG in 14 ML Injection\] for 1 year

Drug: Bosutinib 400 MG Monotherapy; Drug: Bosutinib 400 MG + Atezolizumab 840 MG in 14 ML Injection

Interventions

Bosutinib 400 MG Monotherapy DRUG

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

Also known as: Bosulif

Bosutinib-Atezolizumab Combination

Bosutinib 400 MG + Atezolizumab 840 MG in 14 ML Injection DRUG

12 cycles with bosutinib 400 mg/day plus atezolizumab 1680 mg q4w therapy between the monotherapy bosutinib cycles

Also known as: Bosulif + Tecentriq

Bosutinib-Atezolizumab Combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patient ≥ 18 years of age.
• 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.
• Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
• Newly Patient with Philadelphia chromosome positive chronic phase CML and BCR-ABL1 transcript detected at diagnosis.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
• Adequate hepatic, renal and pancreatic function defined as:
• Total bilirubin within normal range or Direct bilirubin ≤ 1.5 x ULN,
• 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,
• 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.

You may not qualify if:

• Pregnant or lactating women,
• Participation in another clinical trial with any investigational drug within 30 days prior to study enrollment,
• Any prior medical treatment for CML, including tyrosine kinase inhibitors (TKIs), with the exception of hydroxyurea,
• Period of time since CML diagnosis longer than 6 months,
• Hypersensitivity to the active substances or to any of the excipients of the bosutinib and/or atezolizumab formulations,
• Major surgery or radiotherapy within 14 days of enrollment,
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease,
• Concomitant use of or need for medications known to prolong the QTc interval,
• Concomitant use with strong CYP3A inhibitors (ketoconazole, itraconazole, clarithromycin), moderate CYP3A inhibitors (erythromycin, fluconazole, diltiazem), or strong CYP3A inducers (rifampin, carbamazepine, phenytoin),
• History of clinically significant or uncontrolled cardiac disease, including:
• Stage II to IV congestive heart failure (CHF) as determined by the New York Heart Association (NYHA) classification system for heart failure.
• Myocardial infarction within the previous 6 months,
• Symptomatic cardiac arrhythmia requiring treatment,
• Diagnosed or suspected congenital or acquired prolonged QT history or prolonged QTc. (QTcF should not exceed 500 msec),
• Grade III or IV fluid retention,

Sponsors & Collaborators

• Fundacion Espanola para la Curacion de la Leucemia Mieloide Cronica: lead
• Pfizer: collaborator
• Roche Farma, S.A: collaborator

Study Sites (2)

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase

Interventions

bosutinib; atezolizumab; Injections

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Valentín García
• Organization: ZERO LMC

jvalentingg@gmail.com

91 336 86 86

Study Officials

• Valentin Garcia, Dr.

  Hospital Ramon y Cajal

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: March 11, 2021
• Study Start: February 24, 2021
• Primary Completion: September 24, 2021
• Study Completion: September 24, 2021
• Last Updated: March 19, 2024
• Results First Posted: March 12, 2024

Record last verified: 2024-02

Locations

ES (2)