- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03735446
Prexasertib in Combination With MEC in Relapsed/Refractory AML and High Risk MDS - a Phase I Trial
Prexasertib in Combination With Mitoxantrone, Etoposide and Cytarabine (MEC) in Relapsed/Refractory Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS) - a Phase I Trial
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This research study is a Phase I clinical trial, which tests the safety of an investigational drug or combination of drugs and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved prexasertib as a treatment for any disease. Prexasertib is a checkpoint kinase 1 (CHK1) inhibitor that is being developed as a treatment for patients with advanced cancer. CHK1 inhibitors work by preventing cancer cells from being able to repair damaged DNA (one of the building blocks of a cell) which then leads to cell death.
The drugs mitoxantrone, etoposide, and cytarabine (MEC) have all been approved by the FDA. MEC is a standard chemotherapy treatment option, commonly used for AML that has not responded to other standard treatment or returned following standard treatment.
In this research study, the investigators are combining prexasertib with MEC therapy to test if it is a safe treatment for AML or MDS that has returned or not responded to standard treatment.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Dana Farber Cancer Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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).
- QTcF value of ≤ 450 msec on screening electrocardiogram (ECG).
- Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months after treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study therapy administration. A negative serum pregnancy test is required for women of child-bearing potential.
- Ability to understand and the willingness to sign a written informed consent document.
- Patients may have had a prior autologous or allogeneic transplant if there is at least 100 days between transplant and screening, and there is no evidence of active graft-versus-host-disease (GvHD) or ongoing requirement for immunosuppressive therapy.
Exclusion Criteria:
- 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.
- Pregnant women are excluded from this study because prexasertib, mitoxantrone, etoposide, and cytarabine are anti-cancer agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study agents, breastfeeding should be discontinued if the mother is treated with prexasertib, mitoxantrone, etoposide, or cytarabine.
- Patients who are known to be seropositive for human immunodeficiency virus (HIV) or hepatitis B or C.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Prexasertib+MEC
|
Checkpoint kinase 1 (CHK1) inhibitor
Other Names:
Standard chemotherapy (topoisomerase inhibitor)
Other Names:
Standard chemotherapy (topoisomerase II inhibitor)
Standard chemotherapy (anti-metabolite)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose Limiting Toxicity
Time Frame: Up to 42 days
|
Toxicities occurring following administration of protocol therapy, measured using CTCAE 5.0 criteria.
|
Up to 42 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 2 Dose
Time Frame: 18 months
|
Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the study drug combination.
|
18 months
|
Overall Response
Time Frame: 30 months
|
Rates of complete remission (CR), complete remission with incomplete count recovery (CRi), and partial remission (PR).
|
30 months
|
Overall Survival
Time Frame: 30 months
|
Assess the overall survival rate for the combination.
|
30 months
|
Duration of Remission
Time Frame: 12 months
|
Time of achievement of CR or CRi to relapse, death, or 1 year (whichever occurs first)
|
12 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Eric S Winer, MD, Dana-Farber Cancer Institute
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 (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Precancerous Conditions
- Syndrome
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Preleukemia
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Etoposide
- Cytarabine
- Mitoxantrone
Other Study ID Numbers
- 18-468
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
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.
Clinical Trials on Acute Myeloid Leukemia
-
University of PennsylvaniaActive, not recruitingAcute Myeloid Leukemia, in Relapse | Acute Myeloid Leukemia, Refractory | Acute Myeloid Leukemia, PediatricUnited States
-
Terrence J Bradley, MDImago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New...RecruitingAcute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Acute Myeloid Leukemia, in RelapseUnited States
-
Bhavana BhatnagarCTI BioPharmaCompletedRecurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Therapy-Related Acute Myeloid LeukemiaUnited States
-
National Cancer Institute (NCI)RecruitingAcute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
Washington University School of MedicineWithdrawnRefractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
-
C. Babis AndreadisGateway for Cancer Research; AVEO Pharmaceuticals, Inc.TerminatedAcute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingAcute Myeloid Leukemia | Recurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingAcute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Therapy-Related Acute Myeloid LeukemiaUnited States
-
Jacqueline Garcia, MDEli Lilly and CompanyCompletedCombination Merestinib and LY2874455 for Patients With Relapsed or Refractory Acute Myeloid LeukemiaRelapsed Adult Acute Myeloid Leukemia | Refractory Adult Acute Myeloid LeukemiaUnited States
-
University of NebraskaNational Cancer Institute (NCI)Active, not recruitingSecondary Acute Myeloid Leukemia | Therapy-Related Acute Myeloid Leukemia | Adult Acute Myeloid LeukemiaUnited States
Clinical Trials on Prexasertib
-
Eli Lilly and CompanyCompletedAdvanced CancerUnited Kingdom
-
Dana-Farber Cancer InstituteEli Lilly and CompanyCompleted
-
Eli Lilly and CompanyCompletedOvarian CancerUnited States, Israel, Spain, Korea, Republic of, Australia, Belgium, United Kingdom, Italy
-
Eli Lilly and CompanyCompletedSmall Cell Lung CancerSpain, United States, Germany, Ukraine, France, Greece, Turkey, Netherlands, United Kingdom, Korea, Republic of
-
Eli Lilly and CompanyCompletedCarcinoma, Non-Small-Cell Lung | Advanced Cancer | Anal Squamous Cell Carcinoma | Squamous Cell Carcinoma | Carcinoma, Squamous Cell of Head and Neck | Lung Squamous Cell Carcinoma Stage IVUnited States
-
Dana-Farber Cancer InstituteCompletedAdvanced CancersUnited States
-
National Cancer Institute (NCI)TerminatedBreast Cancer | Ovarian Cancer | Prostate CancerUnited States
-
Eli Lilly and CompanyCompleted
-
Eli Lilly and CompanyCompletedColorectal Cancer | Metastatic Cancer | Non-small Cell Lung Cancer | Advanced CancerUnited States, Germany
-
Baylor Research InstituteEli Lilly and CompanyCompletedTriple Negative Breast CancerUnited States