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Chronic Phase-Chronic Myeloid LeukemiaPhase 1/2NCT04793399

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

A Phase 1/2 study testing Bosutinib 400 MG Monotherapy and Bosutinib 400 MG + Atezolizumab 840 MG in 14 ML Injection in people with Chronic Phase-Chronic Myeloid Leukemia, run by Fundacion Espanola para la Curacion de la Leucemia Mieloide Cronica at 2 sites in Spain.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Phase-Chronic Myeloid Leukemia
What is being tested?
Bosutinib 400 MG Monotherapy and Bosutinib 400 MG + Atezolizumab 840 MG in 14 ML Injection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
2 sitesSpain
Study dates
24 Feb 2021to 24 Sep 2021
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.

Who cannot join

  • 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,
Show all 26Show fewer
  • 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,
  • Uncontrolled hypomagnesemia or uncorrected symptomatic hypokalemia, due to potential effects on the QTc interval,
  • Uncontrolled or symptomatic hypercalcemia,
  • Recent or ongoing clinically significant gastrointestinal (GI) disorder e.g. Crohn's Disease, Ulcerative Colitis or prior total or partial gastrectomy,
  • Autoimmune or infectious active disease that require treatment,
  • CML patient not in chronic phase at diagnosis,
  • 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,
  • 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,
  • Individuals with an active malignancy,
  • Known seropositivity to human immunodeficiency virus (HIV), current acute or chronic hepatitis B (hepatitis B surface-antigen positive) and/or hepatitis C.
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug.
  • Patients with severe renal impairment

Trial locations and contacts

2 sites in 1 country.

Spain2 sites

  • Hospital Universitario Ramón y Cajal

    Madrid, 28034

  • Hospital Universitario La Paz

    Madrid, 28046

Other trials in Spain

About this study

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

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.

Read the 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.

Being tested
Bosutinib 400 MG Monotherapy, Bosutinib 400 MG + Atezolizumab 840 MG in 14 ML Injection
Medical subject headings
Leukemia, Myeloid, Chronic-Phase

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bosutinib 400 MG MonotherapyDrug

    Also called Bosulif

    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

  • Bosutinib 400 MG + Atezolizumab 840 MG in 14 ML InjectionDrug

    Also called Bosulif + Tecentriq

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

Study groups in NCT04793399
Study groupRoleWhat they receive
Bosutinib-Atezolizumab CombinationExperimentalDrugs 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
Receives: Drug: Bosutinib 400 MG Monotherapy; Drug: Bosutinib 400 MG + Atezolizumab 840 MG in 14 ML Injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: through study completion, up to 7 months

Secondary outcomes (17)

  1. To Evaluate the Molecular Response (MR) Rates

    Ratio of patients that reach a Molecular response

    Measured: 7 months

  2. Percentage of Participants Alive

    Percentage of patients that remain alive at different time-points over the total number or patients

    Measured: 7 months

  3. Number of Confirmed MR4 and MR4.5

    Total number of patients that reach Molecular response 4 (MR4) and Molecular Response 4.5 (MR4.5)

    Measured: 7 months

  4. The Rate of Confirmed MR4 and MR4.5

    Ratio of patients that reach MR4 and MR4.5

    Measured: 7 months

  5. Number of Complete Cytogenetic Responses (CCyR)

    Number of patients that reach a Complete Cytogenetic Responses (CCyR)

    Measured: 7 months

  6. The Rate of Complete Cytogenetic Response (CCyR)

    Ratio of patients that reach a Complete Cytogenetic Responses (CCyR)

    Measured: 7 months

  7. Days to Response (CCyR, MMR, MR4, MR4.5)

    Number of days lasted since the beginning of the treatment upt to reach molecular response.

    Measured: 7 months

  8. 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

    Measured: 7 months

  9. 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

    Measured: 7 months

  10. Number of Overall Surviving Patients

    Number of the overall surviving patients

    Measured: 7 months

  11. Number of Progression-free Survival Patients

    The following events are considered disease progression:

    • Acelerated Phase.
    • Blast Crisis.
    • CML-related death.

    Measured: 7 months

  12. Number of Failure-free Survival Patients

    Number of the failure-free survival patients

    Measured: 7 months

  13. Number of Event-free Survival Patients

    Number of the event-free survival patients

    Measured: 7 months

  14. Phenotypical Assays of Cell Characterization

    Phenotypical assays of the cell characterization

    Measured: 7 months

  15. Phenotypical Assays of Differentiation, Maturation and Proliferation NK Cells Markers

    Phenotypical assays of the differentiation, maturation and proliferation NK cells markers

    Measured: 7 months

  16. Phenotypical Assays of CD4+ T Cells Activation Markers

    Phenotypical assays of the CD4+ T cells activation markers

    Measured: 7 months

  17. 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+).

    Measured: 7 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Mar 2021
  2. Study start24 Feb 2021
  3. Primary completion24 Sep 2021
  4. Study completion24 Sep 2021

Why it stopped: The study has been prematurely terminated due to the onset of 2 dose limiting toxicities in 2 patients.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04793399
Sponsor's protocol ID
ZEROLMC-01
Status last verified
Feb 2024
First submitted
19 Jan 2021
Last updated
19 Mar 2024
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Bosutinib 400 MG Monotherapy and Bosutinib 400 MG + Atezolizumab 840 MG in 14 ML Injection in people with Chronic Phase-Chronic Myeloid Leukemia, run by Fundacion Espanola para la Curacion de la Leucemia Mieloide Cronica at 2 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety Profile of Bosutinib 400 mg Daily in Combination With Atezolizumab in Participants With Chronic Myeloid Leukemia as First Line Treatments (time frame: through study completion, up to 7 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04793399.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2024.

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