Onvansertib in Combination With Either Low-dose Cytarabine or Decitabine in Adult Patients With Acute Myeloid Leukemia (AML)

NCT ID: NCT03303339

Last Updated: 2023-02-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-17
• Study Completion Date: 2021-11-17

Brief Summary

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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Onvansertib

Intervention Type: DRUG

Onvansertib orally

Cytarabine

Intervention Type: DRUG

subcutaneously

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.

Group Type: EXPERIMENTAL

Onvansertib

Intervention Type: DRUG

Onvansertib orally

Decitabine

Intervention Type: DRUG

intravenously

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.

Group Type: EXPERIMENTAL

Onvansertib

Intervention Type: DRUG

Onvansertib orally

Decitabine

Intervention Type: DRUG

intravenously

Interventions

Onvansertib

Onvansertib orally

Intervention Type: DRUG

Cytarabine

subcutaneously

Intervention Type: DRUG

Decitabine

intravenously

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cardiff Oncology

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of California Los Angeles

Los Angeles, California, United States

Yale University

New Haven, Connecticut, United States

University of Kansas Cancer Center

Westwood, Kansas, United States

Allina Health Virginia Piper Cancer Institute

Minneapolis, Minnesota, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Virginia Cancer Specialists - Fairfax Office

Fairfax, Virginia, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Countries

United States

References

Hagege A, Ambrosetti D, Boyer J, Bozec A, Doyen J, Chamorey E, He X, Bourget I, Rousset J, Saada E, Rastoin O, Parola J, Luciano F, Cao Y, Pages G, Dufies M. The Polo-like kinase 1 inhibitor onvansertib represents a relevant treatment for head and neck squamous cell carcinoma resistant to cisplatin and radiotherapy. Theranostics. 2021 Sep 21;11(19):9571-9586. doi: 10.7150/thno.61711. eCollection 2021.

Reference Type: DERIVED

PMID: 34646387 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1201-6416

Identifier Type: OTHER

Identifier Source: secondary_id

TROV-052

Identifier Type: -

Identifier Source: org_study_id