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Acute Myeloid Leukemia (AML)Phase 1NCT02181660

Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of ASP2215 in Japanese Patients With Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1 study testing Gilteritinib in people with Acute Myeloid Leukemia (AML), run by Astellas Pharma Inc at 5 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The objectives of this study are to determine the safety and tolerability of ASP2215 as well as the maximum tolerated dose (MTD) based on the onset of dose limiting toxicity (DLT) and/or determine the recommended dose (RD) of ASP2215 for the next phase in subjects with relapsed or treatment-refractory acute myeloid… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia (AML)
What is being tested?
Gilteritinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
5 sitesJapan
Study dates
16 Jun 2014to 27 Jun 2016
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Subject is defined as morphologically documented primary or secondary acute myeloid leukemia (AML) according to the World Health Organization (WHO) criteria (2008) and fulfills one of the following:
  • Refractory to prior induction chemotherapy
  • Relapsed after achieving remission with prior therapy
  • Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  • Subject's interval from prior treatment to the time of study drug administration is at least 14 days for antineoplastic agents other than ASP2215 (except for hydroxyurea, which is given to control blast cells).
  • Subject's interval from prior treatment to the time of study drug (ASP2215) administration is at least 5 half-lives (if the half-life is unknown, 14 days) for other investigational products or drugs used for immunosuppressive therapy posthematopoietic stem cell transplantation (HSCT).

Who cannot join

  • Subject was diagnosed with acute promyelocytic leukemia (APL).
  • Subject has breakpoint cluster region-abelson (BCR-ABL)-positive leukemia (chronic myelogenous leukemia in blast crisis)
  • Subject has active malignant tumors other than AML or myelodysplastic syndrome (MDS)
  • Subject has persistent non-hematological toxicities of ≥ Grade 2 (CTCAE v4), with symptoms and objective findings, due to prior AML treatment (including chemotherapy, kinase inhibitors, immunotherapy, investigational products, radiation therapy, and surgery)
  • Subject has received hematopoietic stem cell transplant (HSCT) and falls under either of the following:
  • Is within 2 months of transplant
Show all 18Show fewer
  • Has persistent and clinically significant graft-versus-host disease requiring treatment
  • Has persistent non-hematological toxicities of ≥ Grade 2 related to the transplant
  • Subject has clinically active central nervous system leukemia
  • Subject has disseminated intravascular coagulation (DIC)
  • Subject has had major surgery within 28 days prior to the first study drug administration
  • Subject has had radiation therapy within 28 days prior to the first study drug administration
  • Subject has congestive heart failure of NYHA class 3 or 4, or subject with a past history of congestive heart failure of NYHA class 3 or 4 and in whom echocardiogram or Multiple Gate Acquisition (MUGA) scan performed within 3 months prior to screening or at screening showed a left ventricular ejection fraction (LVEF) of < 45%.
  • Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of CYP3A4 or of P-gp with such exceptions of antibiotics, antifungals, and antivirals that are considered absolutely essential for prevention or treatment of infections and for which the physician judged that there are no interchangeable drugs.
  • Subject requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR receptors or sigma nonspecific receptors, with the exception of drugs that are considered absolutely essential for treatment of the subject.
  • Subject has an active uncontrollable infection
  • Subject is known to have human immunodeficiency virus (HIV) infection
  • Subject has active hepatitis B or C or other active hepatic disorders

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Japan5 sites

  • Site JP00002

    Aichi

  • Site JP00003

    Fukuoka

  • Site JP00001

    Gunma

  • Site JP00004

    Tokyo

  • Site JP00005

    Tokyo

Other trials in Japan

About this study

Official title: A Phase 1 Open-label, Dose-escalation Study Investigating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ASP2215 in Japanese Patients With Relapsed or Refractory Acute Myeloid Leukemia

The objectives of this study are to determine the safety and tolerability of ASP2215 as well as the maximum tolerated dose (MTD) based on the onset of dose limiting toxicity (DLT) and/or determine the recommended dose (RD) of ASP2215 for the next phase in subjects with relapsed or treatment-refractory acute myeloid leukemia (AML).

Read the detailed description

This study will be conducted to determine the safety, tolerability, PK, PD, and efficacy of single and repeated oral dosing of ASP2215 once daily in patients with relapsed or refractory AML. After the determination of the MTD and/or RD, an expansion cohort might be set to further investigate the safety and efficacy of ASP2215.

This study will consist of a single-dose period (Cycle 0, 2 days) and a repeated-dose period (Cycle 1 and subsequent cycles, each cycle consisting of 28 days). The enrolled subjects will orally receive their assigned single dose in Cycle 0 (Day -2), followed by a 2-day observation period (dosing day inclusive). In Cycle 1 and subsequent cycles (one cycle is defined as 28 days), the subjects will receive oral ASP2215 once daily repeatedly until one of the discontinuation criteria is met. Another dosing regimen may be considered such as dosing twice daily based on the safety and PK data that will become available.

In this study, the Bayesian-Continual Reassessment Method (hereinafter, Bayesian-CRM) will be used as a reference for dose-escalation procedures, and based on the onset of DLTs, the RD level of the subsequent cohort will be set higher or lower. DLTs will be assessed during Cycle 0 and Cycle 1 (30 days).

ASP2215 may be escalated by one dose level if the subject meets the criteria at the end of each cycle after Cycle 1 and the investigator/sub-investigator judges escalation of ASP2215 is of clinical benefit. Dose reduction of ASP2215 will be considered if study drug-related toxicities are observed in a subject.

Being tested
Gilteritinib
Keywords
AML, Acute myeloid leukemia, Gilteritinib, ASP2215
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • GilteritinibDrug

    Also called ASP2215

    oral

Study groups in NCT02181660
Study groupRoleWhat they receive
Dose Escalation CohortExperimentalASP2215
Receives: Drug: Gilteritinib

What is being measured

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

  1. Safety and Tolerability assessed through adverse events to determine maximum tolerated dose

    Measured: Up to 17 months

Secondary outcomes (25)

  1. Response Rate

    Response Rate includes following parameters; CR rate, composite CR [CR + CRp + CRi] rate, overall response rate [CRc + PR], duration of response

    Measured: Up to 16 months

  2. Pharmacokinetics of ASP2215 in plasma: AUCinf

    Area under the concentration-time curve from the time of dosing extrapolated to time infinity

    Measured: Cycle 0 Day -2 through Cycle 1 Day 1

  3. Pharmacokinetics of ASP2215 in plasma: AUClast

    Area under the concentration-time curve from the time of dosing to the last measurable concentration

    Measured: Cycle 0 Day -2 through Cycle 1 Day 1

  4. Pharmacokinetics of ASP2215 in plasma: AUC24

    Area under the plasma concentration time curve from time 0 to 24 hours

    Measured: Cycle 0 Day -2 through Cycle 1 Day 1

  5. Pharmacokinetics of ASP2215 in plasma: AUC48

    Area under the plasma concentration time curve from time 0 to 48 hours

    Measured: Cycle 0 Day -2 through Cycle 1 Day 1

  6. Pharmacokinetics of ASP2215 in plasma: Cmax

    Maximum concentration

    Measured: Cycle 0 Day -2 through Cycle 1 Day 1 and Cycle 1 Day 28

  7. Pharmacokinetics of ASP2215 in plasma: C24

    Concentration at 24 hours

    Measured: Cycle 0 Day -2 through Cycle 1 Day 1 and Cycle 1 Day 28

  8. Pharmacokinetics of ASP2215 in plasma: CLF

    Oral clearance

    Measured: Cycle 0 Day -2 through Cycle 1 Day 1 and Cycle 1 Day 28

  9. Pharmacokinetics of ASP2215 in plasma: Lambda z

    Terminal first order elimination rate constant

    Measured: Cycle 0 Day -2 through Cycle 1 Day 1

  10. Pharmacokinetics of ASP2215: tmax

    Time to attain Cmax

    Measured: Cycle 0 Day -2 through Cycle 1 Day 1 and Cycle 1 Day 28

  11. Pharmacokinetics of ASP2215 in plasma: t1/2

    Apparent terminal elimination half-life

    Measured: Cycle 0 Day -2 through Cycle 1 Day 1

  12. Pharmacokinetics of ASP2215 in plasma: Vz/F

    Apparent volume of distribution during the terminal elimination phase after oral dosing

    Measured: Cycle 0 Day -2 through Cycle 1 Day 1

  13. Pharmacokinetics of ASP2215 in plasma: AUCtau

    Area under the plasma concentration time curve during a dosing interval

    Measured: Cycle 1 Day 28

  14. Pharmacokinetics of ASP2215 in plasma: PTR

    Peak-trough ratio

    Measured: Cycle 1 Day 28

  15. Pharmacokinetics of ASP2215 in plasma: Rac(AUC)

    Accumulation ratio calculated using the area under the concentration-time curve

    Measured: Cycle 1 Day 28

  16. Pharmacokinetics of ASP2215 in plasma: Rac(Cmax)

    Accumulation ratio calculated using the maximum concentration

    Measured: Cycle 1 Day 28

  17. Pharmacokinetics of ASP2215 in plasma: Rac derived t1/2

    t1/2 derived from accumulation index

    Measured: Cycle 1 Day 28

  18. Pharmacokinetics of ASP2215 in plasma: Ctrough

    Plasma trough concentration

    Measured: Cycle 1 Day 8, Day 15, Day 22, Day 28 and Day 29

  19. Pharmacokinetics of ASP2215 in urine: Ae24

    Amount of drug excreted in urine from time 0 to 24 hours

    Measured: Cycle 0 Day -2 through Cycle 1 Day 1

  20. Pharmacokinetics of ASP2215 in urine: Ae48

    Amount of drug excreted in urine from time 0 to 48 hours

    Measured: Cycle 0 Day -2 through Cycle 1 Day 1

  21. Pharmacokinetics of ASP2215 in urine: Ae24%

    Fraction of drug excreted into urine from time 0 to 24 hours as % of dose

    Measured: Cycle 0 Day -2 through Cycle 1 Day 1

  22. Pharmacokinetics of ASP2215 in urine: Ae48%

    Fraction of drug excreted into urine from time 0 to 48 hours as % of dose

    Measured: Cycle 0 Day -2 through Cycle 1 Day 1

  23. Pharmacokinetics of ASP2215 in urine: CLR

    Renal clearance

    Measured: Cycle 0 Day -2 through Cycle 1 Day 1 and Cycle 1 Day 28

  24. Pharmacokinetics of ASP2215 in urine: Aetau

    Amount of drug excreted in urine during a dosing interval

    Measured: Cycle 1 Day 28

  25. Pharmacokinetics of ASP2215 in urine: Aetau %

    Fraction of drug excreted in urine during a dosing interval

    Measured: Cycle 1 Day 28

Timeline

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

  1. First posted4 Jul 2014 (estimated)
  2. Study start16 Jun 2014
  3. Primary completion27 Jun 2016
  4. Study completion27 Jun 2016

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02181660
Sponsor's protocol ID
2215-CL-0102
Status last verified
Oct 2024
First submitted
2 Jul 2014
Last updated
6 Nov 2024
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Gilteritinib in people with Acute Myeloid Leukemia (AML), run by Astellas Pharma Inc at 5 sites in Japan.

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 6 inclusion and 18 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: finished, as of the sponsor's last update on 6 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Japan. 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 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.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 and Tolerability assessed through adverse events to determine maximum tolerated dose (time frame: Up to 17 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 NCT02181660.

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 6 Nov 2024.

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