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A Study of ONO-7475 in Patients With Acute Leukemias

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ClinicalTrials.gov Identifier: NCT03176277
Recruitment Status : Recruiting
First Posted : June 5, 2017
Last Update Posted : August 19, 2019
Sponsor:
Information provided by (Responsible Party):
Ono Pharmaceutical Co. Ltd

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Acute Leukemia Drug: ONO-7475 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 26, 2017
Estimated Primary Completion Date : December 18, 2019
Estimated Study Completion Date : March 8, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia

Arm Intervention/treatment
Experimental: ONO-7475: dose escalation
Successive dose escalation cohorts to determine MTD
Drug: ONO-7475
ONO-7475 tablets




Primary Outcome Measures :
  1. Incidence, nature, and severity of (serious) Adverse Events [ Time Frame: Up to 12 months ]
    To determine the safety and tolerability of ONO-7475

  2. Clinically significant ophthalmology examinations [ Time Frame: Up to 12 months ]
    To determine the safety and tolerability of ONO-7475

  3. Clinically significant electrocardiogram (ECG) [ Time Frame: Up to 12 months ]
    To determine the safety and tolerability of ONO-7475


Secondary Outcome Measures :
  1. Determination of Maximum Tolerated Dose (MTD) [ Time Frame: Up to 12 months ]
    As assessed by the incidence, nature, and severity of (serious) Adverse Events

  2. Determination of recommended pharmacological dose [ Time Frame: Up to 12 months ]
    As assessed by the Plasma inhibitory activity (PIA)

  3. Pharmacokinetics (Tmax) [ Time Frame: Day 1 and Day 28 of Cycle 1 ]
    Assessment of the time to reach maximum observed plasma concentration of ONO-7475.

  4. Pharmacokinetics (Cmax) [ Time Frame: Day 1 and Day 28 of Cycle 1 ]
    Assessment of the maximum plasma concentration of ONO-7475.

  5. Pharmacokinetics (AUC) [ Time Frame: Day 1 and Day 28 of Cycle 1 ]
    Assessment of the plasma area under the curve (day 1 and 28) of ONO-7475.

  6. Pharmacokinetics (T1/2) [ Time Frame: Day 1 and Day 28 of Cycle 1 ]
    Assessment of the plasma decay half life of ONO-7475.

  7. Pharmacokinetics (Ctrough) [ Time Frame: Cycle 1 predose Day 7 and Day 15 ]
    Assessment of the trough concentration of ONO-7475 in the plasma.

  8. Pharmacokinetics (Cmax) - Food effect [ Time Frame: Day 57 (Cycle 3 Day 1) ]
    Assessment of the food effect on the maximum plasma concentration of ONO-7475.

  9. Pharmacokinetics (Tmax) - - Food effect [ Time Frame: Day 57 (Cycle 3 Day 1) ]
    Assessment of the food effect on the time to reach maximum observed plasma concentration of ONO-7475.

  10. Pharmacokinetics (AUC) - Food effect [ Time Frame: Day 57 (Cycle 3 Day 1) ]
    Assessment of the food effect on the plasma area under the curve of ONO-7475

  11. Pharmacokinetics (T1/2) - Food effect [ Time Frame: Day 57 (Cycle 3 Day 1) ]
    Assessment of the food effect on the plasma decay half life of ONO-7475.

  12. Pharmacokinetics (Ctrough) - Food effect [ Time Frame: Day 57 (Cycle 3 Day 1) ]
    Assessment of the food effect on the trough concentration of ONO-7475 in the plasma.

  13. Pharmacodynamics of ONO-7475 [ Time Frame: Up to 12 months ]
    Assessment of the pharmacodynamic activity of ONO-7475 as assessed by a PIA assay (pAxl/pMer inhibition).

  14. Overall response rate (ORR) [ Time Frame: Up to 12 months ]
    CR + CRi + MLFS or PR

  15. Duration of response (DOR) [ Time Frame: Up to 12 months ]
    Duration in months from PR, CRi and CR

  16. Event-free survival [ Time Frame: Up to 12 months ]
    Time of treatment failure, progression or patient death from any cause

  17. Complete Response without minimal residual disease (MRD) [ Time Frame: Up to 12 months ]
    Assessed by flow cytometry for patients who achieve CR



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 >2.5g/dL For any patient laboratory values outside the ranges outlined above that are considered due to the patient's underlying disease (AML or ALL), the patient may be enrolled into the study following consultation between the Investigator and the Sponsor's Medical Officer if the patient is likely to benefit from receiving ONO-7475 (based on the Investigator's assessment)
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 as assessed during the screening period and then again anytime during the 2-day period immediately preceding the start of ONO-7475 dosing.
  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. Patients with active Central Nervous System (CNSL) Leukemia
  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 liver disease, including active viral or other hepatitis, current alcohol abuse, or severe 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 14 days or with any licensed drug within five half-lives, prior to the first ONO-7475 dosing.
  13. Prior AML or ALL therapy (non-experimental) within 14 days or five half-lives whichever is longer, prior to the first dose of ONO-7475 (except those permitted in the protocol) and no residual toxicity from the prior therapy hindering of the ONO-7475 dosing.
  14. Prior radiotherapy within 21 days of screening. Localized radiation therapy 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 prior to first dose of ONO-7475
  18. Active malignancy, other than AML (Parts A and B) or ALL (Part C), requiring systemic therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03176277


Contacts
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Contact: ONO Pharma UK Ltd +44 (0)2074214920 ctinfo@ono-uk.co.uk

Locations
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United States, Alabama
University of Alabama at Birmingham Not yet recruiting
Birmingham, Alabama, United States, 35294
Principal Investigator: Nikolas Papadantonakis, MD         
United States, California
University of Southern California Not yet recruiting
Los Angeles, California, United States, 90033
Principal Investigator: George Yaghmour, MD         
University of California Recruiting
Los Angeles, California, United States, 90095
Principal Investigator: Joshua Sasine, MD         
United States, Kansas
University of Kansas Cancer Center Terminated
Fairway, Kansas, United States, 66205
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Principal Investigator: Dale Bixby, MD         
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Principal Investigator: Eunice Wang, MD         
Weill Medical College of Cornell University Not yet recruiting
New York, New York, United States, 10021
Principal Investigator: Gail Roboz, MD         
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Principal Investigator: Margaret Kasner, MD         
United States, South Carolina
Medical University of South Carolina - Hollins Cancer Center Recruiting
Charleston, South Carolina, United States, 29425
Principal Investigator: Brian Hess, MD         
Sponsors and Collaborators
Ono Pharmaceutical Co. Ltd
Investigators
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Study Director: ONO Pharma UK Ltd Drug Development Division

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Responsible Party: Ono Pharmaceutical Co. Ltd
ClinicalTrials.gov Identifier: NCT03176277     History of Changes
Other Study ID Numbers: ONO-7475-01
First Posted: June 5, 2017    Key Record Dates
Last Update Posted: August 19, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ono Pharmaceutical Co. Ltd:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
MER
MERTK
TYRO3
AXL
AML
de novo AML
Relapsed/ Refractory AML
TAM

Additional relevant MeSH terms:
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Leukemia
Acute Disease
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes