Clinical Trials /

A Study of ONO-7475 in Patients With Acute Leukemias

NCT03176277

Description:

This study will determine the safety and maximum tolerated dose of ONO-7475 in patients with relapsed or refractory acute leukemia and evaluate the efficacy of ONO-7475 in patients with newly diagnosed AML

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of ONO-7475 in Patients With Acute Leukemias
  • Official Title: A Phase I Open Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Clinical Efficacy of ONO-7475 in Patients With Acute Leukemias

Clinical Trial IDs

  • ORG STUDY ID: ONO-7475-01
  • NCT ID: NCT03176277

Conditions

  • Acute Leukemia

Interventions

DrugSynonymsArms
ONO-7475ONO-7475: dose escalation

Purpose

This study will determine the safety and maximum tolerated dose of ONO-7475 in patients with relapsed or refractory acute leukemia and evaluate the efficacy of ONO-7475 in patients with newly diagnosed AML

Trial Arms

NameTypeDescriptionInterventions
ONO-7475: dose escalationExperimentalSuccessive dose escalation cohorts to determine MTD
  • ONO-7475

Eligibility Criteria

        Inclusion Criteria:

          1. Patients aged ≥18 years at time of screening

          2. Written informed consent by the patient (or legal representative) prior to admission
             to this study. In addition any locally required authorization (Health Insurance
             Portability and Accountability Act in the USA [HIPAA], obtained from the patient prior
             to performing any protocol-related procedures, including screening evaluations.

          3. Adequate renal and hepatic function defined as:

               -  Total bilirubin within 1.5 x ULN, except those with Gilberts syndrome for whom
                  this must be <3 x ULN

               -  AST(SGOT) and ALT(SGPT) <2.5 x ULN

               -  Calculated Creatinine clearance>/= 45ml/min

               -  Serum Albumin >3g/dL

          4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          5. Life expectancy of at least 3 months

          6. Sexually active female patients of childbearing potential and sexually active male
             patients must agree to use an effective method of birth control (e.g., barrier methods
             with spermicides, oral or parenteral contraceptives and/or intrauterine devices)
             during the entire duration of the study and for 4 months after final administration of
             study drug. Note that sterility in female patients must be confirmed in the patients'
             medical records and be defined as any of the following: surgical hysterectomy with
             bilateral oophorectomy, bilateral tubular ligation, natural menopause with last menses
             >1 year ago; radiation induced oophorectomy with last menses >1 year ago; chemotherapy
             induced menopause with last menses >1 year ago.

          7. Male patients must use a condom from the time of the first administration of ONO-7475
             until 4 months following administration of the last dose.

        8. Diagnosis of AML according to WHO criteria 2016.

        9. Relapsed or refractory AML patients with at least 5% blasts by bone marrow biopsy or
        aspirate, or at least 1% blasts in peripheral blood, not likely to benefit from standard
        salvage chemotherapy.

        10. All patients must have received at least one prior therapy - 1 cycle of cytarabine
        containing regimen or 2 cycles of hypomethylating agent - before determination of
        refractory status (defined as response duration less than 3 months or no response)

        Exclusion Criteria:

          1. Primary disease involving the Central Nervous System (CNS)

          2. QTcF prolongation defined as a QTcF interval >470 msec or other significant ECG
             abnormalities including 2nd degree (type II) or 3rd degree AV block or bradycardia
             (ventricular rate <50 beats/min).

          3. Clinically significant history of liver disease, including viral or other hepatitis,
             current alcohol abuse, or cirrhosis

          4. HIV/active Hepatitis B or C infection

          5. Retinal disease (e.g. retinitis pigmentosa including Mertk mutations), retinal
             hemorrhage or any disorder which may inhibit follow up for retinal toxicity

          6. Serious intercurrent medical or psychiatric illness that will prevent participation or
             compliance with study procedures, including serious active infection

          7. Acute promyelocytic leukemia (FAB M3 classification)

          8. Patients not recovered to Grade 1 or stabilized from the effects (excluding alopecia)
             of any prior therapy for their malignancies

          9. Concurrent treatment with other investigational drugs.

         10. Daily requirement for corticosteroids ≥ prednisone 10 mg/day or equivalent.

         11. Prior hematopoietic stem cell transplantation within 12 weeks of the first dose of
             study treatment or ongoing immunosuppressive therapy for graft versus host disease

         12. Participation in another clinical trial with any investigational drug within 30 days
             prior to study entry.

         13. Prior AML or ALL therapy (non-experimental) within 28 days of first dose of ONO-7475
             (except those permitted in the protocol)

         14. Prior radiotherapy within 21 days of screening. Localized radiation therapy to a
             single site within the last 7 days is acceptable. Concurrent radiotherapy is not
             permitted.

         15. Patients undergoing current treatments for other cancers

         16. Pregnant or lactating women

         17. Proliferative disease (WBC > 30 x 109 /L) (confirmed at time of study entry prior to
             first dose)

         18. Diagnosed or treated for a malignancy other than AML within 5 years, or who were
             previously diagnosed with a malignancy other than AML and have any radiographic or
             biochemical marker evidence of malignancy. Note: Patients with completely resected
             basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy at
             any time are not excluded
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence, nature, and severity of (serious) Adverse Events
Time Frame:Up to 12 months
Safety Issue:
Description:To determine the safety and tolerability of ONO-7475

Secondary Outcome Measures

Measure:Determination of Maximum Tolerated Dose (MTD)
Time Frame:Up to 12 months
Safety Issue:
Description:As assessed by the incidence, nature, and severity of (serious) Adverse Events
Measure:Determination of recommended pharmacological dose
Time Frame:Up to 12 months
Safety Issue:
Description:As assessed by the Plasma inhibitory activity (PIA)
Measure:Pharmacokinetics (Tmax)
Time Frame:Day 1 and Day 28 of Cycle 1
Safety Issue:
Description:Assessment of the time to reach maximum observed plasma concentration of ONO-7475.
Measure:Pharmacokinetics (Cmax)
Time Frame:Day 1 and Day 28 of Cycle 1
Safety Issue:
Description:Assessment of the maximum plasma concentration of ONO-7475.
Measure:Pharmacokinetics (AUC)
Time Frame:Day 1 and Day 28 of Cycle 1
Safety Issue:
Description:Assessment of the plasma area under the curve (day 1 and 28) of ONO-7475.
Measure:Pharmacokinetics (T1/2)
Time Frame:Day 1 and Day 28 of Cycle 1
Safety Issue:
Description:Assessment of the plasma decay half life of ONO-7475.
Measure:Pharmacokinetics (Ctrough)
Time Frame:Cycle 1 predose Day 7 and Day 15
Safety Issue:
Description:Assessment of the trough concentration of ONO-7475 in the plasma.
Measure:Pharmacokinetics (Cmax) - Food effect
Time Frame:Day 57 (Cycle 3 Day 1)
Safety Issue:
Description:Assessment of the food effect on the maximum plasma concentration of ONO-7475.
Measure:Pharmacokinetics (Tmax) - - Food effect
Time Frame:Day 57 (Cycle 3 Day 1)
Safety Issue:
Description:Assessment of the food effect on the time to reach maximum observed plasma concentration of ONO-7475.
Measure:Pharmacokinetics (AUC) - Food effect
Time Frame:Day 57 (Cycle 3 Day 1)
Safety Issue:
Description:Assessment of the food effect on the plasma area under the curve of ONO-7475
Measure:Pharmacokinetics (T1/2) - Food effect
Time Frame:Day 57 (Cycle 3 Day 1)
Safety Issue:
Description:Assessment of the food effect on the plasma decay half life of ONO-7475.
Measure:Pharmacokinetics (Ctrough) - Food effect
Time Frame:Day 57 (Cycle 3 Day 1)
Safety Issue:
Description:Assessment of the food effect on the trough concentration of ONO-7475 in the plasma.
Measure:Pharmacodynamics of ONO-7475
Time Frame:Up to 12 months
Safety Issue:
Description:Assessment of the pharmacodynamic activity of ONO-7475 as assessed by a PIA assay (pAxl/pMer inhibition).
Measure:Overall response rate (ORR)
Time Frame:Up to 12 months
Safety Issue:
Description:CR + CRi + MLFS or PR
Measure:Duration of response (DOR)
Time Frame:Up to 12 months
Safety Issue:
Description:Duration in months from PR, CRi and CR
Measure:Progression free survival (PFS)
Time Frame:Up to 12 months
Safety Issue:
Description:Duration in months from first study treatment to disease progression or death
Measure:Event-free survival
Time Frame:Up to 12 months
Safety Issue:
Description:Time of treatment failure, progression or patient death from any cause
Measure:Minimal residual disease (MRD)
Time Frame:Up to 12 months
Safety Issue:
Description:Assessed by flow cytometry for patients who achieve CR

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ono Pharmaceutical Co. Ltd

Trial Keywords

  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myeloid, Acute
  • MER
  • MERTK
  • TYRO3
  • AXL
  • AML
  • de novo AML
  • Relapsed/ Refractory AML
  • TAM

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