Description:
The purpose of the phase 1b/2 study is to determine whether Onvansertib given orally daily
for 5 consecutive days every 28 days is safe and tolerable in adult patients who have
relapsed/refractory Acute Myeloid Leukemia (AML), or are ineligible for intensive induction
therapy, and to determine the maximum tolerated dose and recommended phase 2 dose of
Onvansertib in combination with decitabine or Onvansertib in combination with low-dose
cytarabine. In the phase 2 portion of the study, Onvansertib in combination with decitabine
will be studied to provide further data on the safety profile of the combination and to
preliminarily assess the activity of the chosen combination in patients with untreated AML
who are not candidates for aggressive induction therapy, or who have received one prior
treatment for their AML.
Title
- Brief Title: Onvansertib in Combination With Either Low-dose Cytarabine or Decitabine in Adult Patients With Acute Myeloid Leukemia (AML)
- Official Title: 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)
Clinical Trial IDs
- ORG STUDY ID:
TROV-052
- SECONDARY ID:
U1111-1201-6416
- NCT ID:
NCT03303339
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Onvansertib | | Phase 1b: Onvansertib + decitabine |
Cytarabine | | Phase 1b: Onvansertib + low-dose cytarabine |
Decitabine | | Phase 1b: Onvansertib + decitabine |
Purpose
The purpose of the phase 1b/2 study is to determine whether Onvansertib given orally daily
for 5 consecutive days every 28 days is safe and tolerable in adult patients who have
relapsed/refractory Acute Myeloid Leukemia (AML), or are ineligible for intensive induction
therapy, and to determine the maximum tolerated dose and recommended phase 2 dose of
Onvansertib in combination with decitabine or Onvansertib in combination with low-dose
cytarabine. In the phase 2 portion of the study, Onvansertib in combination with decitabine
will be studied to provide further data on the safety profile of the combination and to
preliminarily assess the activity of the chosen combination in patients with untreated AML
who are not candidates for aggressive induction therapy, or who have received one prior
treatment for their AML.
Trial Arms
Name | Type | Description | Interventions |
---|
Phase 1b: Onvansertib + low-dose cytarabine | Experimental | 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. | |
Phase 1b: Onvansertib + decitabine | Experimental | 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. | |
Phase 2: Onvansertib + decitabine | Experimental | 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. | |
Eligibility Criteria
Inclusion Criteria:
1. Disease Status and Prior Therapy:
1. Histologically confirmed AML with >20% blasts
2. 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.
3. 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
2. Age ≥18 years
3. ECOG performance status ≤2
4. Participants must be willing and able to review, understand, and provide written
consent before starting any study-specific procedures or therapy.
5. 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
1. 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
2. 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:
1. Treatment-related AML or acute promyelocytic leukemia (APL)
2. Active malignancies within 12 months with the exception of those with a negligible
risk of metastasis or death
3. Clinical evidence of active central nervous system leukemia at the time of screening
4. Alanine aminotransferase and/or aspartate aminotransferase ≥2.5 x upper limit of
normal (ULN)
5. Total bilirubin > 2.0 mg/dL (or > 3.0 mg/dL in participants with documented Gilbert
syndrome)
6. Serum creatinine ≥2.0 mg/dL
7. New York Heart Association Class III or IV heart disease, active ischemia or any other
uncontrolled cardiac condition, or hypertensive or metabolic condition
8. Myocardial infarction in the previous 12 weeks (from the start of treatment)
9. Resting left ventricular ejection fraction <50% at the time of screening
10. 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.
11. Active and uncontrolled disease (other than AML) or infection as judged by the
treating physician
12. 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)
13. 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.
14. 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of Participants With Dose Limiting Toxicity (DLT) |
Time Frame: | Baseline up to 30 days after last dose of study drug (up to 27 months) |
Safety Issue: | |
Description: | DLT is defined as an adverse reaction or suspected adverse reaction, during the 28 days according to the Common Terminology Criteria for Adverse Events (CTCAE). |
Secondary Outcome Measures
Measure: | Phase 2: Rate of achievement of a morphologic Leukemia-free (MLF) State |
Time Frame: | Baseline and end of trial (up to 27 months) |
Safety Issue: | |
Description: | Defined as bone marrow (BM) <5% blasts in an aspirate with spicules (a BM biopsy should be performed if spicules are absent) and no blasts with Auer rods or persistence of extramedullary disease. |
Measure: | Phase 2: Rate of partial response (PR) |
Time Frame: | Baseline up to 30 days after last dose of study drug (up to 27 months) |
Safety Issue: | |
Description: | 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 |
Measure: | Phase 2: Duration of response (DOR) |
Time Frame: | Baseline and end of trial (up to 27 months) |
Safety Issue: | |
Description: | Time from documentation of response until documentation of recurrence of or progression of disease. |
Measure: | Phase 2: Event-free survival (EFS) |
Time Frame: | Baseline and end of trial (up to 27 months) |
Safety Issue: | |
Description: | Time from enrollment until disease progression or death from any cause. |
Measure: | Phase 2: Overall survival (OS) |
Time Frame: | Baseline up to 30 days after last dose of study drug (up to 27 months) |
Safety Issue: | |
Description: | Time from enrollment until death from any cause |
Measure: | Pharmacokinetic parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib |
Time Frame: | Up to 24 months |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetic parameter: Minimum Observed Plasma Trough Concentration (Cmin) for Onvansertib |
Time Frame: | Up to 24 months |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetic parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib |
Time Frame: | Up to 24 months |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetic parameter: Area under the curve over the first 24 hours AUC(0-24) for Onvansertib |
Time Frame: | Up to 24 months |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetic parameter: Plasma terminal elimination half-life (t1/2) for Onvansertib |
Time Frame: | Up to 24 months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Cardiff Oncology |
Trial Keywords
- PLK1
- PLK Inhibitor
- Onvansertib
Last Updated
May 27, 2021