- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03303339
Onvansertib in Combination With Either Low-dose Cytarabine or Decitabine in Adult Patients With Acute Myeloid Leukemia (AML)
A Phase 1b/2 Study of PCM-075 (Onvansertib) in Combination With Either Low-Dose Cytarabine or Decitabine in Subjects With Acute Myeloid Leukemia (AML)
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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California
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Los Angeles, California, United States, 90095
- University of California Los Angeles
-
-
Connecticut
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New Haven, Connecticut, United States, 06510
- Yale University
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Kansas
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Westwood, Kansas, United States, 66205
- University of Kansas Cancer Center
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Minnesota
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Minneapolis, Minnesota, United States, 55407
- Allina Health Virginia Piper Cancer Institute
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New York
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Buffalo, New York, United States, 14263
- Roswell Park Cancer Institute
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Texas
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Dallas, Texas, United States, 75390
- University of Texas Southwestern Medical Center
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Houston, Texas, United States, 77030
- MD Anderson Cancer Center
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Virginia
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Fairfax, Virginia, United States, 22031
- Virginia Cancer Specialists - Fairfax Office
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Washington
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Seattle, Washington, United States, 98109
- Seattle Cancer Care Alliance
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Disease Status and Prior Therapy:
- Histologically confirmed AML with >20% blasts
- Phase 1b: Participants with AML who are refractory to or have relapsed after initial treatment for their disease, with no more than three prior lines of therapy. Participants who have received prior treatment with cytarabine or decitabine are not excluded.
- Phase 2:
i. Participants with AML who are refractory to, or have relapsed after, initial treatment for their disease, with no more than one prior line of therapy, and are judged not to be candidates for re-induction therapy that includes hematopoietic cell transplantation. Participants who have received prior cytarabine or decitabine are not excluded.
OR
ii. Participants with newly diagnosed, untreated AML ineligible for, or who have refused, standard intensive induction therapy
- Age ≥18 years
- ECOG performance status ≤2
- Participants must be willing and able to review, understand, and provide written consent before starting any study-specific procedures or therapy.
All men and women must agree to practice effective contraception during the entire study period and after discontinuing study drug, unless documentation of infertility exists
- Sexually active, fertile women must use two effective forms of contraception (abstinence, intrauterine device, oral contraceptive, or double barrier device) from the time of informed consent and until at least 6 months after discontinuing study drug
- Sexually active men and their sexual partners must use effective contraceptive methods from the time of participant informed consent and until at least 3 months after discontinuing study drug
Exclusion Criteria:
- Treatment-related AML or acute promyelocytic leukemia (APL)
- Active malignancies within 12 months with the exception of those with a negligible risk of metastasis or death
- Clinical evidence of active central nervous system leukemia at the time of screening
- Alanine aminotransferase and/or aspartate aminotransferase ≥2.5 x upper limit of normal (ULN)
- Total bilirubin > 2.0 mg/dL (or > 3.0 mg/dL in participants with documented Gilbert syndrome)
- Serum creatinine ≥2.0 mg/dL
- New York Heart Association Class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition, or hypertensive or metabolic condition
- Myocardial infarction in the previous 12 weeks (from the start of treatment)
- Resting left ventricular ejection fraction <50% at the time of screening
- QT (Interval from the beginning of the QRS complex to the end of the T wave on an electrocardiogram) interval with Fridericia's correction [QTcF] >450 milliseconds. The QTcF should be calculated as the arithmetic mean of the QTcF on triplicate ECGs. In the case of potentially correctible causes of QT prolongation (e.g., medications, hypokalemia), the triplicate ECG may be repeated once during screening and that result may be used to determine eligibility.
- Active and uncontrolled disease (other than AML) or infection as judged by the treating physician
- Treatment with systemic therapy for the primary disease within 14 days (except for hydroxyurea or isolated doses of cytarabine or decitabine for white blood cell control)
- Grade 2 or greater toxicities from prior therapy, except for Grade 2 toxicities that are not expected to resolve and that in the judgment of the Investigator do not pose a significant safety risk to subject participation.
- Participants with any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the participant's ability to sign the informed consent form or his/her ability to cooperate and participate in the study, or to interfere with the interpretation of the results.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Phase 1b: Onvansertib + low-dose cytarabine
Onvansertib, administered in escalating doses orally Day 1 through Day 5 every 28 days (1 cycle) in combination with cytarabine, which will be administered in all cohorts as 20 mg/m^2 subcutaneously, once daily on Day 1 through Day 10 every 28 days (1 cycle).
Onvansertib administration, in combination with cytarabine, will be initiated at a starting dose of 12 mg/m^2 orally, daily for 5 days.
Onvansertib dose will be escalated in successive cohorts until the recommended phase 2 dose is achieved.
|
Onvansertib orally
subcutaneously
|
Experimental: Phase 1b: Onvansertib + decitabine
Onvansertib will be administered in escalating doses orally, Day 1 through Day 5 every 28 days (1 cycle) in combination with decitabine, administered consistently in all cohorts as 20 mg/m^2 intravenously over 1 hour on Day 1 through Day 5 every 28 days (1 cycle).
Onvansertib administration, in combination with decitabine, will be initiated at a starting dose of 12 mg/m^2 orally, daily for 5 days (Day 1 through Day 5).
Onvansertib dose will be escalated in successive cohorts until the recommended phase 2 dose is achieved.
|
Onvansertib orally
intravenously
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Experimental: Phase 2: Onvansertib + decitabine
Onvansertib recommended phase 2 dose, orally Day 1 through Day 5 every 28 days (1 cycle) and decitabine, administered consistently as 20 mg/m^2 intravenously over 1 hour on Day 1 through Day 5 every 28 days (1 cycle), with treatment modifications or delays based on return of hematopoietic function to baseline or Grade ≤1 toxicity for optimal subject management.
|
Onvansertib orally
intravenously
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Who Experienced Dose Limiting Toxicities (DLT)
Time Frame: Up to Day 28 of Cycle 1
|
Dose-limiting toxicities were defined as events related to onvansertib that were considered an adverse reaction or suspected adverse reaction during the first cycle of therapy and that fulfilled one of the following: Hematologic (persistent pancytopenia resistant to current standards of care that continues for ≥42 days and is not related to leukemic infiltration or another cause unrelated to study therapy) or Non-Hematologic (any Grade 3 abnormalities that persist >7 days without decreasing in severity despite standards of care, are clinically significant, or that are Grade 4 and symptomatic).
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Up to Day 28 of Cycle 1
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Number of Participants With Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status
Time Frame: Baseline and end of study (approximately up to up to 27 months)
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ECOG performance status was determined using 6-point scale from 0-5, with 0 meaning a participant was fully active/able to carry on all pre-disease activities without restriction and 5 meaning the participant was deceased.
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Baseline and end of study (approximately up to up to 27 months)
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Phase 2: Number of Participants Who Achieved a Complete Response (CR)
Time Frame: Up to 27 months
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Complete Response also includes Complete Response with Incomplete Blood Count Recovery (CRi). Complete response is defined by the following criteria: Morphologic leukemia-free state plus:
Complete response with incomplete blood count recovery meets all criteria for CR except for either neutropenia (ANC <1000/mm3) or thrombocytopenia (<100,000/mm3) but must include transfusion independence. |
Up to 27 months
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Number of Participants With Adverse Events (AEs)
Time Frame: Baseline up to 30 days after last dose of study drug (up to 27 months)
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Any clinically significant change in electrocardiogram (ECG), physical examination findings, body weight, vital signs, and laboratory parameters were recorded as Adverse Events.
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Baseline up to 30 days after last dose of study drug (up to 27 months)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 2: Number of Participants Who Achieved a Morphologic Leukemia-free (MLF) State
Time Frame: Up to 27 months
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Defined as bone marrow (BM) <5% blasts in an aspirate with spicules and no blasts with Auer rods or persistence of extramedullary disease.
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Up to 27 months
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Phase 2: Number of Participants With Partial Response (PR)
Time Frame: Up to 27 months
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PR criteria includes all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate and a normalization of blood counts.
|
Up to 27 months
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Phase 2: Duration of Response (DOR)
Time Frame: Up to 27 months
|
Duration of Response (DOR) is the time (in months) from the first response of CR, CRi or PR until recurrence of or progression of disease (or death).
MLF State is also included as a response when calculating DOR.
Responding subjects without death or progression will be censored at the date of their last evaluable disease assessment.
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Up to 27 months
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Phase 2: Event-free Survival (EFS)
Time Frame: 12 Months
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EFS is defined as the time from enrollment until disease progression or death from any cause and reported as the proportion of participants event free at 12 months.
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12 Months
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Phase 2: Overall Survival (OS)
Time Frame: 12 Months
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OS is defined as the time from enrollment until death from any cause and reported as the proportion of participants alive at 12 months.
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12 Months
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Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib
Time Frame: Cycle 1: Days 1 and 5
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Cycle 1: Days 1 and 5
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Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib
Time Frame: Cycle 1: Days 1 and 5
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Cycle 1: Days 1 and 5
|
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Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib
Time Frame: Cycle 1: Days 1 and 5
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Cycle 1: Days 1 and 5
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Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib
Time Frame: Cycle 1: Days 1 and 5
|
Cycle 1: Days 1 and 5
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protein Kinase Inhibitors
- Decitabine
- Cytarabine
- Onvansertib
Other Study ID Numbers
- TROV-052
- U1111-1201-6416 (Other Identifier: WHO)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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