AML-02: Omacetaxine With Standard-of-Care Induction With Cytarabine & Idarubicin in Newly-Diagnosed AML Patients

NCT02440568 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 2015-0181
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This is a dose escalation study to evaluate Omacetaxine when given in combination with a standard induction regimen of "7+3" (cytarabine for Days 1-7 and Idarubicin for Days 1-3) in patients with newly diagnosed acute myelogenous leukemia (AML).

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Optimally Tolerated Dose

  The primary endpoint is determination of the optimally active and safe dose (OD) of Omacetaxine when added to the standard-of-care induction chemotherapy for AML and estimation of the efficacy and response rate. OD will be defined as a dose level at which fewer than 30% of patients experience hematologic toxicity and greater than 50% of patients achieve a CR (50% is an accepted CR rate in AML when using a single induction).

  Within 50 days (duration of hematologic recovery)

Secondary Outcomes (5)

• Toxicity: Describe by the Adverse Events as Assessed by the CTCAE Grading

  Up to 6 months after last dose of Omacetaxine

• Time to Hematologic Recovery

  Within 6 months of last dose of Omacetaxine

• Overall Participant Survival

  3 years

• Event Free Survival

  6 months

• Progression Free Survival

  3 years

Study Arms (4)

Cohort 1: Omacetaxine at Dose level at 0.625mg/m^2

EXPERIMENTAL

Patients will receive Omacetaxine at Dose level 0.625mg/m\^2, Cytarabine and Idarubicin as part of the treatment plan. Study participants will follow in outpatient clinic at least every 2 months for a total of 6 months. A final study visit will occur 6 months (+/-1 week) after the last dose of Omacetaxine. This visit will end study participation unless there is ongoing toxicity that is at least possibly related to study treatment. In this case, the patient will be followed as medically appropriate until resolution or stabilization of the adverse event.

Drug: Cytarabine; Drug: Idarubicin; Drug: Omacetaxine mepesuccinate

Cohort 2: Omacetaxine at Dose level at 1.25mg/m^

EXPERIMENTAL

Patients will receive Omacetaxine at Dose level 1.25mg/m\^2, Cytarabine and Idarubicin as part of the treatment plan. Study participants will follow in outpatient clinic at least every 2 months for a total of 6 months. A final study visit will occur 6 months (+/-1 week) after the last dose of Omacetaxine. This visit will end study participation unless there is ongoing toxicity that is at least possibly related to study treatment. In this case, the patient will be followed as medically appropriate until resolution or stabilization of the adverse event.

Drug: Cytarabine; Drug: Idarubicin; Drug: Omacetaxine mepesuccinate

Cohort 3: Omacetaxine at Dose level at 2.0mg/m^

EXPERIMENTAL

Patients will receive Omacetaxine at Dose level 2.0mg/m\^2, Cytarabine and Idarubicin as part of the treatment plan. Study participants will follow in outpatient clinic at least every 2 months for a total of 6 months. A final study visit will occur 6 months (+/-1 week) after the last dose of Omacetaxine. This visit will end study participation unless there is ongoing toxicity that is at least possibly related to study treatment. In this case, the patient will be followed as medically appropriate until resolution or stabilization of the adverse event.

Drug: Cytarabine; Drug: Idarubicin; Drug: Omacetaxine mepesuccinate

Cohort 4: Omacetaxine at Dose level at 3.0mg/m^

EXPERIMENTAL

Patients will receive Omacetaxine at Dose level 3.0mg/m\^2, Cytarabine and Idarubicin as part of the treatment plan. Study participants will follow in outpatient clinic at least every 2 months for a total of 6 months. A final study visit will occur 6 months (+/-1 week) after the last dose of Omacetaxine. This visit will end study participation unless there is ongoing toxicity that is at least possibly related to study treatment. In this case, the patient will be followed as medically appropriate until resolution or stabilization of the adverse event.

Drug: Cytarabine; Drug: Idarubicin; Drug: Omacetaxine mepesuccinate

Interventions

Cytarabine DRUG

Cytarabine (100mg/m\^2/day) in 1000ml NS as a continuous IV infusion over 24 hours x 7 days.

Also known as: Cytosine arabinoside, Ara-C, Cytosar

Cohort 1: Omacetaxine at Dose level at 0.625mg/m^2; Cohort 2: Omacetaxine at Dose level at 1.25mg/m^; Cohort 3: Omacetaxine at Dose level at 2.0mg/m^; Cohort 4: Omacetaxine at Dose level at 3.0mg/m^

Idarubicin DRUG

Idarubicin (12 mg/m\^2/day) IVPB in 100 mL NS over 15 minutes daily from Days 1 to 3.

Also known as: Idamycin PFS, Idamycin®

Cohort 1: Omacetaxine at Dose level at 0.625mg/m^2; Cohort 2: Omacetaxine at Dose level at 1.25mg/m^; Cohort 3: Omacetaxine at Dose level at 2.0mg/m^; Cohort 4: Omacetaxine at Dose level at 3.0mg/m^

Omacetaxine mepesuccinate DRUG

Omacetaxine administered subcutaneously Q12 hours Days 1 to 7. Dose level 0.625mg/m\^2

Cohort 1: Omacetaxine at Dose level at 0.625mg/m^2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed, untreated patients with AML according to the WHO classification for AML. Prior short-term therapy (≤7 days) with hydroxyurea, steroids, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors, azacitidine, ATRA), or hematopoietic growth factors is allowed. A single or two-day dose of cytarabine (up to 3 g/m\^2) for emergency use is also allowed as prior therapy.
• Patients age 18 to 70 years old who meet diagnostic criteria for AML according to the WHO classification for AML.
• Previously untreated AML (≥20% blasts). Note that prior short-term therapy (≤7 days) with hydroxyurea, steroids, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors, azacitidine, ATRA), or hematopoietic growth factors is allowed. A single or two-day dose of cytarabine (up to 3 g/m2) for emergency use is also allowed as prior therapy.
• ECOG performance status of 0-3
• Adequate organ function, if not suspected to be due to AML, within 14 days of study registration, defined as:
• Total bilirubin ≤ 2.0 x ULN (unless due to hemolysis) AST and ALT ≤ 3 X ULN (unless believed to be due to tumor involvement) Serum Creatinine ≤ 1.5 x ULN Creatinine Clearance \> 30 ml/min
• Negative urine or serum pregnancy test in females. Patients of reproductive potential (males and females) must consent to and practice double-barrier methods of contraception during treatment and for 12 weeks following the last dose of Omacetaxine. Adequate contraception is defined as double-barrier protection (i.e., condom plus spermicide in combination with a diaphragm, cervical/vault cap, or intrauterine device). Birth control pills, birth control patches and/or injections of hormones to prevent pregnancy are not considered an adequate method of preventing pregnancy, and double-barrier protection is required while on study and for 12 weeks after last dose. Patients will be instructed to notify the investigator if pregnancy is discovered either during or within 12 weeks of completing treatment with Omacetaxine. This also applies to male patients whose partners become pregnant while the patient is on study or within the 12 week period after the last dose of study drug.
• Patients must be willing and able to review, understand, and provide written consent before starting therapy.

You may not qualify if:

• Acute promyelocytic leukemia.
• Investigational drug within 4 weeks of study entry.
• Cardiac insufficiency grade III or IV New York Heart Association (NYHA)
• Female subjects who are pregnant or breast feeding.
• Patients who are HIV positive.
• Active uncontrolled infection or severe systemic infection (enrollment is possible after control of infection).
• Concurrent malignancy (other than AML) with an estimated life expectancy less than two years and requiring active therapy.
• Psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up.
• Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or medically relevant active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
• Pregnant or breastfeeding: Omacetaxine is a Pregnancy Category D medication and has caused embryo-fetal death in animals. Confirmation that the subject is not pregnant must be established by a negative urine β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.

Sponsors & Collaborators

• University of Illinois at Chicago: lead
• Teva Pharmaceuticals USA: collaborator

Study Sites (1)

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cytarabine; Idarubicin; Homoharringtonine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Harringtonines; Alkaloids; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings

Results Point of Contact

• Title: Dr. John Quigley
• Organization: University of Illinois at Chicago

seanq@uic.edu

312-413-1300

Study Officials

• John Quigley, MD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 7, 2015
• First Posted: May 12, 2015
• Study Start: June 5, 2015
• Primary Completion: November 30, 2018
• Study Completion: November 30, 2018
• Last Updated: July 6, 2021
• Results First Posted: July 6, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)