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Acute Myeloid LeukemiaPhase 1NCT02236013

A Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia

A Phase 1 study testing Gilteritinib, Idarubicin and Cytarabine in people with Acute Myeloid Leukemia, run by Astellas Pharma Global Development, Inc. at 10 sites in United States.

Completed

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

Official record
Search all trials

Trial summary

The purpose of this study is to describe the dose limiting toxicities (DLT) and define the maximum tolerated dose (MTD) of ASP2215 when combined with cytarabine/idarubicin or daunorubicin remission induction in a 7+3 schedule. Safety and tolerability of ASP2215 will also be evaluated. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Gilteritinib, Idarubicin and Cytarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
10 sitesUnited States
Study dates
7 Jan 2015to 26 Jul 2021
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 has a diagnosis of previously-untreated de novo acute myeloid leukemia (AML) according to WHO classification (2008) documented within 28 days prior to enrollment.
  • Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Subject must meet the following criteria as indicated on the clinical laboratory tests.
  • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x institutional upper limit normal (ULN)
  • Total serum bilirubin ≤ 1.5 x institutional ULN
  • Serum creatinine ≤ 1.5 x institutional ULN or an estimated glomerular filtration rate (eGFR) of > 50 ml/min as calculated by the Modification of Diet in Renal Disease (MDRD) equation.
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  • Subject is suitable for oral administration of study drug.
  • Female subject must be either:
  • Of non-child bearing potential:
  • post-menopausal (defined as at least 1 year without any menses) prior to Screening, or
  • documented surgically sterile or status post hysterectomy (at least 1 month prior to Screening)
  • Or, if of childbearing potential,
  • must agree not to try to become pregnant during the study and for 180 days after the final study drug administration, and
  • must have a negative urine pregnancy test at Screening, and
  • must use two forms of birth control* (at least one of which must be a barrier method) starting at Screening and throughout the study period and for 180 days after the final study drug administration. *Acceptable forms of birth control include:
  • Established use of oral, injected or implanted hormonal methods of contraception.
  • Placement of an intrauterine device (IUD) or intrauterine system (IUS).
  • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
  • Female subject must not be breastfeeding at Screening or during the study period, and for 60 days after the final study drug administration.
  • Female subject must not donate ova starting at Screening and throughout the study period, and for 180 days after the final study drug administration.
  • Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control* (one of which must be a barrier method) starting at Screening and continue throughout the study period and for 120 days after the final study drug administration.
  • Male subject must not donate sperm starting at Screening and throughout the study period and for 120 days after the final study drug administration.
  • Subject agrees not to participate in another interventional study while on treatment.

Who cannot join

  • Subject was diagnosed as acute promyelocytic leukemia (APL) or AML with good risk cytogenetics; t(8;21), inv(16) or t(16;16). (Subjects with pending cytogenetics that require treatment may enroll. Any subject that is found to have good risk cytogenetics after initiation of treatment will discontinue ASP2215 and be taken off trial).
  • Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
  • Subject has active malignant tumors other than AML or myelodysplastic syndrome (MDS).
  • Subject has received previous therapy for AML, with the exception of the following:
  • Emergency leukapheresis;
  • Emergency treatment for hyperleukocytosis with hydroxyurea for ≤ 10 days;
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  • Preemptive treatment with retinoic acid prior to exclusion of APL ≤ 7 days;
  • Growth factor or cytokine support;
  • Steroids for the treatment of hypersensitivity or transfusion reactions.
  • Subject has clinically active central nervous system leukemia.
  • Subject has disseminated intravascular coagulation abnormality (DIC).
  • Subject has had major surgery within 4 weeks prior to the first study dose.
  • Subject has radiation therapy within 4 weeks prior to the first study dose.
  • Subject has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subject with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram performed within 3 months prior to study entry results in a left ventricular ejection fraction that is ≥ 45%.
  • Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A.
  • Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of P glycoprotein (P-gp) with the exception of drugs that are considered absolutely essential for the care of the subject.
  • Subject requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR receptors or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
  • Subject has an active uncontrolled infection.
  • Subject is known to have human immunodeficiency virus infection.
  • Subject has active hepatitis B or C, or other active hepatic disorder.
  • Subject has any condition which makes the subject unsuitable for study participation (e.g. ophthalmic conditions such as advanced cataracts).
  • Subject has Fridericia-corrected QT interval (QTcF) > 450 ms at Screening based on central reading.
  • Subject has Long corrected QT interval (QTc) Syndrome at Screening.
  • Subject has hypokalemia and hypomagnesemia at Screening (defined as values below institutional lower limit of normal [LLN]).

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites
  • Site US10001

    Baltimore, Maryland, 21231

  • Site US10004

    Chicago, Illinois, 60611

  • Site US10014

    Cleveland, Ohio, 44106

  • Site US10003

    Los Angeles, California, 90095

  • Site US10013

    New Haven, Connecticut, 06520

  • Site US10002

    New York, New York, 10032

  • Site US10019

    Oklahoma City, Oklahoma, 73104

  • Site US10006

    Philadelphia, Pennsylvania, 19104

  • Site US10010

    San Antonio, Texas, 78229

  • Site US10009

    Westwood, Kansas, 66205

Other trials in United States

About this study

Official title: A Phase 1 Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia

The purpose of this study is to describe the dose limiting toxicities (DLT) and define the maximum tolerated dose (MTD) of ASP2215 when combined with cytarabine/idarubicin or daunorubicin remission induction in a 7+3 schedule. Safety and tolerability of ASP2215 will also be evaluated. This study will also characterize the pharmacokinetics (PK) of ASP2215 when given in combination with cytarabine/idarubicin or cytarabine/daunorubicin remission induction and high-dose cytarabine (HiDAC) consolidation therapy in newly diagnosed acute myeloid leukemia as well as evaluate the effect of ASP2215 on the PK of cytarabine.

Read the detailed description

This is a four-part trial. In Part 1, subjects will be enrolled to successive cohorts to determine the maximum tolerated dose (MTD). Dose escalation decision will be made based on DLTs that occur after the first dose of ASP2215 during remission induction. The treatment will consist of three distinct periods: remission induction, consolidation and maintenance.

In Part 2, subjects will be enrolled into an expansion cohort. Subjects will receive ASP2215 at the MTD established in Part 1 or recommended expansion dose, and will also receive remission induction, consolidation and maintenance therapy. The DLT observation period during the expansion cohort will be from the start of dosing of ASP2215 during the first remission induction treatment until Day 21 of the first consolidation cycle or before the start of the second consolidation cycle, whichever is sooner; as well as from the start of maintenance treatment until Day 28 of the second maintenance cycle. If testing at a dose level must be stopped, then a lower dose may be tested for remaining subjects to be enrolled.

In Part 3, two cohorts will be enrolled to evaluate an alternative anthracycline and ASP2215 schedule. During remission induction, ASP2215 dosing will begin at day 8 and continue for 14 days to day 21. Subjects will be hospitalized during remission induction therapy while receiving chemotherapy.

In cohort 3A, some subjects will be enrolled to receive 7+3 regimen consisting of cytarabine and an alternative antracycline, daunorubicin. During remission induction subjects will receive a 7+3 induction regimen consisting of daunorubicin IV infusion on days 1 through 3 and cytarabine as a continuous infusion on days 1 through 7.

In cohort 3B, some subjects will be enrolled to receive 7+3 regimen consisting of cytarabine and idarubicin at an alternative dosing schedule for ASP2215 during remission induction. During remission induction subjects will receive a 7+3 induction regimen consisting of idarubicin by IV infusion on days 1 through 3 and cytarabine as a continuous infusion on days 1 through 7.

For Part 3, if day 21 bone marrow evaluation shows residual blasts and the bone marrow is not aplastic, a second induction cycle with the same regimen will be given starting at least 7 days after last dose of ASP2215 and no later than day 35 of the first induction cycle. Consolidation and Maintenance therapy follow the same schedule and dosage outlined in Part 1.The DLT observation period for dose escalation decisions will be from the start of ASP2215 administration during the first remission induction treatment until day 42 of the last remission induction treatment cycle or before the start of the first consolidation cycle, whichever is sooner.

A subject that receives less than 80% of the intended dose of any of the study drugs during the remission induction period may be replaced.

Part 3 may be expanded for additional subjects to ensure at least some subjects are FLT3 + in each of the Alternative Anthracycline and Schedule Cohorts.

In Part 4, the effect of continuous ASP2215 exposure during consolidation will be evaluated.

During remission induction, subjects will receive a 7+3 induction regimen consisting of daunorubicin on days 1 through 3 and cytarabine as a continuous infusion on days 1 through 7. ASP2215 will be given at the designated dose, once daily starting on day 8, and continued for 14 days until day 21. If day 21 bone marrow evaluation shows residual blasts and the bone marrow is not aplastic, a second induction cycle with the same regimen will be given starting at least 7 days after last dose of ASP2215 and no later than day 35 of the first induction cycle.

Consolidation therapy will follow the same schedule and dosage outlined in Part 1 except for the ASP2215 schedule. ASP2215 will be given at the designated dose, once daily starting on day 1 up to day 56, which is the maximum number of days between each consolidation cycle.

Subjects may participate in up to 3 consolidation cycles. Maintenance therapy and posttreatment will also follow the same schedule and dosage outlined in Part 1.

The DLT observation period will be during the first consolidation cycle only. This will be from the start of ASP2215 administration (consolidation cycle 1 day 1) until consolidation cycle 1 day 56 or the next chemotherapy cycle, whichever is sooner.

Being tested
Gilteritinib, Idarubicin, Cytarabine, Daunorubicin
Keywords
ASP2215, Daunorubicin, Gilteritinib, Acute Myeloid Leukemia, Idarubicin, Cytarabine
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

  • IdarubicinDrug

    lyophilized powder administered intravenously

  • CytarabineDrug

    solution administered intravenously

  • DaunorubicinDrug

    solution administered intravenously

Study groups in NCT02236013
Study groupRoleWhat they receive
ASP2215 Dose Escalation (Part 1)ExperimentalSuccessive dose escalation cohorts will determine the maximum tolerated dose (MTD)
Receives: Drug: Gilteritinib; Drug: Idarubicin; Drug: Cytarabine
ASP2215 Dose Expansion (Part 2)ExperimentalOnce the MTD has been established in Part 1, up to 20 subjects will be enrolled into an expansion cohort
Receives: Drug: Gilteritinib; Drug: Idarubicin; Drug: Cytarabine
Alternative Anthracycline and Schedule (Part 3)ExperimentalIn Part 3, two cohorts will be enrolled to evaluate an alternative anthracycline and ASP2215 schedule
Receives: Drug: Gilteritinib; Drug: Idarubicin; Drug: Cytarabine; Drug: Daunorubicin
Continuous ASP2215 Exposure during Consolidation (Part 4)ExperimentalDuring Consolidation, ASP2215 will be given daily on day 1 up to day 56.
Receives: Drug: Gilteritinib; Drug: Idarubicin; Drug: Cytarabine; Drug: Daunorubicin

What is being measured

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

  1. Safety and tolerability assessed by development of dose limiting toxicities, adverse events, and define maximum tolerated dose (MTD)

    Measured: up to 2.5 years after start of the treatment

Secondary outcomes (2)
  1. Pharmacokinetics profile of ASP2215: AUC24, Cmax, Ctrough and tmax

    Area under the curve at 24 hours (AUC24), maximum concentration (Cmax), minimum concentration (Ctrough), and time after dosing when Cmax occurs (tmax)

    Measured: Days 8, 11, 17, and 28 for remission induction and Days 1, 2, and 15 for consolidation

  2. Pharmacokinetics of cytarabine: Css

    Steady state concentration (Css)

    Measured: Days 3 and 8

Timeline

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

  1. First posted10 Sep 2014 (estimated)
  2. Study start7 Jan 2015
  3. Primary completion26 Jul 2021
  4. Study completion26 Jul 2021

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02236013
Sponsor's protocol ID
2215-CL-0103
Status last verified
Oct 2024
First submitted
8 Sep 2014
Last updated
5 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated device
No
Individual data sharing
Yes: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
Expanded access
Available

Publications

  • Pratz KW, Cherry M, Altman JK, Cooper BW, Podoltsev NA, Cruz JC, Lin TL, Schiller GJ, Jurcic JG, Asch A, Wu R, Hill JE, Gill SC, James AJ, Rich ES, Hasabou N, Perl AE, Levis MJ. Gilteritinib in Combination With Induction and Consolidation Chemotherapy and as Maintenance Therapy: A Phase IB Study in Patients With Newly Diagnosed AML. J Clin Oncol. 2023 Sep 10;41(26):4236-4246. doi: 10.1200/JCO.22.02721. Epub 2023 Jun 28.

    PubMed 37379495

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Gilteritinib, Idarubicin and Cytarabine in people with Acute Myeloid Leukemia, run by Astellas Pharma Global Development, Inc. at 10 sites in United States.

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 23 inclusion and 24 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 5 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 10 sites in United States. 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 by development of dose limiting toxicities, adverse events, and define maximum tolerated dose (MTD) (time frame: up to 2.5 years after start of the treatment). 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 NCT02236013, which also lists 1 linked publication.

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 5 Nov 2024.

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