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Study of PTC299 in Relapsed/Refractory Acute Leukemias

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03761069
Recruitment Status : Recruiting
First Posted : December 3, 2018
Last Update Posted : April 8, 2021
Information provided by (Responsible Party):
PTC Therapeutics

Brief 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 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.

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute AML Drug: PTC299 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1B Study of PTC299 in Relapsed/Refractory Acute Leukemias
Actual Study Start Date : October 29, 2018
Estimated Primary Completion Date : May 31, 2021
Estimated Study Completion Date : June 30, 2021

Arm Intervention/treatment
Experimental: PTC299
PTC299 will be administered orally once daily (QD) for each 28-day cycle.
Drug: PTC299
PTC299 will be administered per the treatment arm description

Primary Outcome Measures :
  1. Number of Participants Who Discontinued Study Drug Due to Adverse Event (AE) [ Time Frame: From Screening to 50 days post treatment ]

Secondary Outcome Measures :
  1. Time to Maximum Plasma Concentration (Tmax) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 6 Months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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.

Exclusion Criteria:

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:

  • 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.


  • Known hypersensitivity to study drug or its excipients.


  • 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)

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 identifier (NCT number): NCT03761069

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Contact: Patient Advocacy Corporate Relations 1-866-562-4620

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United States, Colorado
Rocky Mountain Cancer Center Recruiting
Aurora, Colorado, United States, 80012
Contact: John Burke, Dr.   
United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06510
Contact: Thomas Prebet    203-785-4699   
United States, Michigan
Henry Ford Health System Recruiting
Detroit, Michigan, United States, 48202
Contact: Ahmad Mattour    313-916-3721   
United States, New Jersey
Rutgers, Cancer Institute of NJ Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Dale Schaar    732-235-2465   
United States, New York
Columbia Recruiting
New York, New York, United States, 10032
Contact: Joseph Jurcic    212-317-4224   
University of Rochester MC Recruiting
Rochester, New York, United States, 14642
Contact: Michael Becker    545-275-4099   
United States, North Carolina
Duke Cancer Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Cheryl Morgan Maxey         
Principal Investigator: Harry Erba, MD         
United States, Ohio
Gabrail Cancer Center Recruiting
Canton, Ohio, United States, 44718
Contact: Nashat Gabrail    330-492-3345   
Oncology Hematology Care, Inc. Recruiting
Cincinnati, Ohio, United States, 45236
Contact: Edward Broun, Dr.   
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Aziz Nazha    216-445-7009   
United States, Rhode Island
Rhode Island, Miriam Hospital Recruiting
Providence, Rhode Island, United States, 02903
Contact: John Reagan    401-444-3234   
United States, Tennessee
SCRI Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: William Donnellan    615-986-7604   
United States, Texas
Texas Oncology, P.A. Recruiting
Austin, Texas, United States, 78705
Contact: Jason Melear, Dr.   
Texas Oncology, P.A. Recruiting
Fort Worth, Texas, United States, 76104
Contact: Stephen Richey, Dr.   
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Gautam Borthakur    713-563-1586   
Texas Oncology, P.A. - San Antonio Medical Center Recruiting
San Antonio, Texas, United States, 78240
Contact: John Renshaw, Dr.   
United States, Washington
Swedish Cancer Institute Recruiting
Seattle, Washington, United States, 91804
Contact: Raya Mawad    206-215-2658   
Sponsors and Collaborators
PTC Therapeutics
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Responsible Party: PTC Therapeutics Identifier: NCT03761069    
Other Study ID Numbers: PTC299-HEM-001-LEU
First Posted: December 3, 2018    Key Record Dates
Last Update Posted: April 8, 2021
Last Verified: March 2021

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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 PTC Therapeutics:
Leukemia, Myeloid
Neoplasms by Histologic Type
Dihydroorotate dehydrogenase (DHODH) inhibitor
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action