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Leukemia, Myeloid, AcutePhase 1NCT03761069

Study of PTC299 (Emvododstat) in Relapsed/Refractory Acute Leukemias

A Phase 1 study testing PTC299 in people with Leukemia, Myeloid, Acute and AML, run by PTC Therapeutics at 17 sites in United States.

Terminated

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

Official record
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Trial summary

This is an open-label, non-randomized, Phase 1b study to evaluate the safety, pharmacokinetics (PK) profiles, and preliminary evidence of antitumor activity of PTC299 and the metabolite, O-desmethyl PTC299, in participants with relapsed/refractory acute myeloid leukemia (AML) who have exhausted standard available… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia, Myeloid, Acute, AML
What is being tested?
PTC299
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
17 sitesUnited States
Study dates
29 Oct 2018to 28 Dec 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

  • Participant must have relapsed/refractory AML and exhausted standard available therapies known to provide clinical benefit.
  • Subjects must be greater than or equal to 18 years of age.
  • Subjects must have Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (≤) 2
  • Women of childbearing potential must be willing to practice a highly-effective method of birth control for up to 50 days after the last dose of study drug.
  • A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control during the study and for up to 50 days after the last dose of study drug.
  • Subjects must be willing to participate to the study, have the ability to understand and adhere to study visit schedule and other protocol procedures, and be able and willing to sign a written informed consent form.

Who cannot join

  • Medical history:
  • Women who are or plan to become pregnant, or who are currently breastfeeding.
  • Persistence of any clinically relevant (Common Terminology Criteria for Adverse Events [CTCAE] Grade 2 or above) toxicities from previous therapy.
  • Active alcohol or drug abuse.
  • Previous drug-induced liver injury.
  • Cardiac assessments:
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  • Uncontrolled congestive heart failure, unstable angina pectoris.
  • History or current evidence of a myocardial infarction during the last 6 months.
  • QTc prolongation greater than (>) 500 milliseconds (msec) (Fridericia formula).
  • Congenitally long QT syndrome or has received any marketed or experimental compound in the last 4 weeks or 5 half-lives (whichever is shorter) prior to entering the study with possible or known effects of QT prolongation. (If equivalent medication is not available, QTc will be closely monitored.)
  • Laboratory assessments:
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) greater than or equal to (≥) 1 * upper limit of normal (ULN).
  • Serum bilirubin ≥ 1 * ULN (except those known to have Gilbert's syndrome).
  • Creatinine clearance ≤45 milliliters per minute (mL/min) (estimated by Cockcroft-Gault or by 24-hour urine collection).
  • Any laboratory abnormality, which in the opinion of the investigator, places the participant at an unacceptably high risk for toxicities.
  • Gastrointestinal (GI) assessments:
  • Liver malignancy (including metastases) or chronic liver disease.
  • History of Gastrointestinal surgery or procedures or conditions that might interfere with the absorption or swallowing of the study drug.
  • Immunologic:
  • Known hypersensitivity to study drug or its excipients.
  • Miscellaneous:
  • Any sign of active uncontrolled infections; any severe chronic disease potentially interfering with the protocol, including human immunodeficiency virus (HIV) infection, or active hepatitis B or C or those with a positive screen for hepatitis A Immunoglobulin M (IgM).
  • Any other malignancies within the past 2 years other than basal cell skin cancer or carcinoma in situ of the cervix.
  • Participant concomitantly receiving any other investigational agents.
  • Systemic chemotherapy within 2 weeks or investigational therapy within 5 half-lives prior to first dose of study drug, unless there is evidence of rapidly progressive disease (in which case the shorter washout of 2 weeks will be followed). For monoclonal antibodies, the washout from prior therapy will be 4 weeks, unless there is evidence of rapidly progressive disease, in which case, the shorter washout period of 2 weeks will be followed. Persistent chronic clinically significant toxicities from prior chemotherapy must not be >Grade 1. Use of hydroxyurea (Hydrea) is permitted up to 24 hours prior to start of study drug for control of proliferative disease. Hydrea treatment may be reinstated during study for control of proliferative disease, as needed, at the discretion of investigator.
  • Participants with AML that has advanced with central nervous system (CNS) involvement.
  • Participant is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.
  • Participants receiving CYP2B6 substrates such as bupropion and methadone.
  • Participants receiving strong CYP3A4 inducers such as carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, and St. John's wort (hypericin) or drugs that are exclusively substrates of CYP3A4.
  • Participant is receiving moderate or strong CYP3A4 inhibitors. (Note: This exclusion criterion is not applicable to subjects participating in sub-study where only subjects who are currently on/require antifungals [prophylaxis/treatment] will be enrolled)

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

United States17 sites

  • Rocky Mountain Cancer Center

    Aurora, Colorado, 80012

  • Texas Oncology, P.A.

    Austin, Texas, 78705

  • Gabrail Cancer Center

    Canton, Ohio, 44718

  • Oncology Hematology Care, Inc.

    Cincinnati, Ohio, 45236

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Duke Cancer Center

    Durham, North Carolina, 27710

  • Texas Oncology, P.A.

    Fort Worth, Texas, 76104

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • SCRI Tennessee Oncology

    Nashville, Tennessee, 37203

  • Rutgers, Cancer Institute of NJ

    New Brunswick, New Jersey, 08903

  • Yale University

    New Haven, Connecticut, 06510

  • Columbia

    New York, New York, 10032

  • Rhode Island, Miriam Hospital

    Providence, Rhode Island, 02903

  • University of Rochester MC

    Rochester, New York, 14642

  • Texas Oncology, P.A. - San Antonio Medical Center

    San Antonio, Texas, 78240

  • Swedish Cancer Institute

    Seattle, Washington, 91804

Other trials in United States

About this study

Official title: Phase 1B Study of PTC299 in Relapsed/Refractory Acute Leukemias

This is an open-label, non-randomized, Phase 1b study to evaluate the safety, pharmacokinetics (PK) profiles, and preliminary evidence of antitumor activity of PTC299 and the metabolite, O-desmethyl PTC299, in participants with relapsed/refractory acute myeloid leukemia (AML) who have exhausted standard available therapies known to provide clinical benefit. The study is designed as a series of cohort-based dose escalations. For each cohort, a minimum of 3 evaluable participants with PK and safety data will be assessed. Additional participants will be recruited if additional PK data are needed to assess mean exposure based on the observed variability.

Being tested
PTC299
Keywords
Leukemia, Myeloid, Neoplasms by Histologic Type, Neoplasms, Dihydroorotate dehydrogenase (DHODH) inhibitor
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia, Myeloid, Neoplasms by Histologic Type, Neoplasms

What participants receive

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

  • PTC299Drug

    Also called Emvododstat

    PTC299 will be administered per the treatment arm description

Study groups in NCT03761069
Study groupRoleWhat they receive
PTC299ExperimentalPTC299 will be administered orally once daily (QD) for each 28-day cycle.
Receives: Drug: PTC299

What is being measured

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

  1. Number of Participants Who Discontinued Study Drug Due to Adverse Event (AE)

    Measured: From Screening to 50 days post treatment

Secondary outcomes (9)

  1. Time to Maximum Plasma Concentration (Tmax) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food

    Measured: Days 1, 15, 28, 57, 71 and 99

  2. Maximum Plasma Concentration (Cmax) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food

    Measured: Days 1, 15, 28, 57, 71 and 99

  3. Area Under the Concentration-Time Curve (AUC) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food

    Measured: Days 1, 15, 28, 57, 71 and 99

  4. Half-life (t1/2) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food

    Measured: Days 1, 15, 28, 57, 71 and 99

  5. Estimate t1/2 of of both PTC299 and O-desmethyl PTC299 During 14-Day Washout Period

    Measured: Day 29 through Day 42

  6. Apparent Clearance (CL/F) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food

    Measured: Days 1, 15, 28, 57, 71 and 99

  7. Apparent Volume of Distribution (Vz/F) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food

    Measured: Days 1, 15, 28, 57, 71 and 99

  8. Accumulation Ratio (R) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food

    Measured: Days 1, 15, 28, 57, 71 and 99

  9. Percentage of Participants Achieving Response Rate/Overall Response Rate Utilizing International Working Group (IWG) Response Criteria for AML

    Measured: Up to 6 Months

Timeline

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

  1. First posted3 Dec 2018
  2. Study start29 Oct 2018
  3. Primary completion28 Dec 2021
  4. Study completion28 Dec 2021

Why it stopped: Sponsor terminated the study.

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
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03761069
Sponsor's protocol ID
PTC299-HEM-001-LEU
Status last verified
Jan 2022
First submitted
29 Nov 2018
Last updated
2 Feb 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PTC299 in people with Leukemia, Myeloid, Acute and AML, run by PTC Therapeutics at 17 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 6 inclusion and 30 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 2 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 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 was stopped early (reason given: Sponsor terminated the study.). Results are not available in the source record.

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?

Number of Participants Who Discontinued Study Drug Due to Adverse Event (AE) (time frame: From Screening to 50 days post 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 NCT03761069.

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 2 Feb 2022.

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