Prexasertib in Combination With MEC in Relapsed/Refractory AML and High Risk MDS - a Phase I Trial

NCT03735446 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 18-468
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying a targeted therapy combined with chemotherapy as a possible treatment for acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS). The drugs involved in this study are:

• Prexasertib (LY2606368)
• Mitoxantrone
• Etoposide
• Cytarabine

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes

Keywords

Acute Myeloid Leukemia; Myelodysplastic Syndromes; AML; MDS; CHK1; MEC; Prexasertib

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity

  Toxicities occurring following administration of protocol therapy, measured using CTCAE 5.0 criteria.

  Up to 42 days

Secondary Outcomes (4)

• Phase 2 Dose

  18 months

• Overall Response

  30 months

• Overall Survival

  30 months

• Duration of Remission

  12 months

Study Arms (1)

Prexasertib+MEC

EXPERIMENTAL

* Cytarabine is administered intravenously on days 1-5. * Etoposide is administered intravenously on days 1-5. * Mitoxantrone is administered intravenously on days 1-5. * Prexasertib is administered intravenously on days 1, 3, and 5.

Drug: Prexasertib; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine

Interventions

Prexasertib DRUG

Checkpoint kinase 1 (CHK1) inhibitor

Also known as: LY2606368

Prexasertib+MEC

Mitoxantrone DRUG

Standard chemotherapy (topoisomerase inhibitor)

Also known as: Novantrone

Prexasertib+MEC

Etoposide DRUG

Standard chemotherapy (topoisomerase II inhibitor)

Prexasertib+MEC

Cytarabine DRUG

Standard chemotherapy (anti-metabolite)

Prexasertib+MEC

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed relapsed or refractory acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS) diagnosed per WHO criteria.
• For refractory AML: refractory as defined per International Working Group (IWG) criteria. Refractory patients must have had ≤ 2 prior induction regimens (hydroxyurea is not considered a prior treatment regimen). "5+2" reinduction at day 14 is not considered a second regimen.
• For relapsed AML: relapse as defined by IWG criteria. Relapsed patients must be first or second relapse (hydroxyurea is not considered a prior treatment regimen).
• For patients with MDS, ≥ 10% myeloblasts in the bone marrow, and no more than 2 prior treatment regimens (hydroxyurea is not considered a prior treatment regimen).
• Patients must be medically eligible to receive mitoxantrone, etoposide, and cytarabine (MEC) therapy.
• Age ≥ 18 years
• ECOG performance status ≤ 2 (Karnofsky ≥60%)
• Patients must have adequate organ function as defined below:
• Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN), OR
• Total bilirubin ≤ 2 × institutional ULN if the participant has a history of Gilbert's syndrome.
• AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN, OR
• AST(SGOT)/ALT(SGPT) ≤ 5 × institutional ULN if elevation is a result of leukemia
• Serum creatinine ≤ 1.5 × institutional ULN, OR
• Creatinine Clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal (calculated via the Cockcroft-Gault equation).
• Left ventricular ejection fraction (LVEF) ≥ 50% on screening echocardiogram (ECHO) or multigated acquisition scan (MUGA).

You may not qualify if:

• Patients who have had chemotherapy, other investigational therapy, radiotherapy, or immune therapy within 2 weeks prior to the first dose of study medication. Hydroxyurea is allowed with no required washout and may be administered up to day 5 of protocol therapy.
• Patients previously treated with MEC chemotherapy.
• Patients who have received a tyrosine kinase inhibitor (TKI) within 5 half-lives of day 1.
• Patients who have had major surgery within 4 weeks prior to the first dose of study medication.
• Patients with acute promyelocytic leukemia.
• Patients with a known personal or family history of long QT syndrome.
• Patients with known CNS leukemia involvement.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to prexasertib, mitoxantrone, etoposide, or cytarabine.
• Patients with a history of a secondary malignancy, with the following exceptions:
• Malignancies that have been curatively treated and have not recurred within the past 2 years
• Adequately treated carcinoma in situ of any type
• Curatively treated non-melanoma skin cancers
• Any other malignancy that has been curatively treated with a low likelihood of recurrence as judged by the treating investigator and agreed upon with the overall principal investigator prior to study entry
• Patients with other secondary malignancies may be allowed to enroll with agreement from the overall principal investigator.
• Uncontrolled intercurrent illness including, but not limited to: uncontrolled active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

prexasertib; Mitoxantrone; Etoposide; Cytarabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Eric S Winer, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 7, 2018
• First Posted: November 8, 2018
• Study Start: January 18, 2019
• Primary Completion: March 29, 2019
• Study Completion: March 29, 2019
• Last Updated: June 12, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)