Testing the Addition of an Anti-cancer Drug, M3814, to the Usual Treatment (Mitoxantrone, Etoposide, and Cytarabine) for Relapsed or Refractory Acute Myeloid Leukemia
A Phase 1 Study of M3814 in Combination With MEC in Patients With Relapsed or Refractory Acute Myeloid Leukemia
4 other identifiers
interventional
48
1 country
15
Brief Summary
This phase I trial studies the best dose and side effects of M3814 when given in combination with mitoxantrone, etoposide, and cytarabine in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). M3814 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as mitoxantrone and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Giving M3814 in combination with mitoxantrone, etoposide, and cytarabine may lower the chance of the acute myeloid leukemia growing or spreading.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started May 2020
Longer than P75 for phase_1
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 10, 2019
CompletedFirst Posted
Study publicly available on registry
June 12, 2019
CompletedStudy Start
First participant enrolled
May 5, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2026
April 13, 2026
January 1, 2026
6.2 years
June 10, 2019
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence of adverse events
Coded according to the Common Terminology Criteria for Adverse Events version 5.
Up to 5 years
Secondary Outcomes (5)
Pharmacokinetic (PK) profile of M3814 in combination with mitoxantrone, etoposide, and cytarabine (MEC)
Days 1 and 5
Overall response rate
Up to 5 years
Duration of CR/CRi
From first documented CR/CRi response to relapse, assessed up to 5 years
Event-free survival
From study entry to treatment failure (lack of response, i.e., no CR or CRi), relapse from CR or CRi, or death from any cause, assessed up to 5 years
Overall survival
From study entry to death from any cause, assessed up to 2 years
Other Outcomes (4)
Rate of early mortality
At 90 days
Rate of allogeneic hematopoietic cell transplantation (HCT)
Up to 5 years
Pharmacodynamic effects of M3814 in combination with MEC
Up to 5 years
- +1 more other outcomes
Study Arms (1)
Treatment (peposertib, mitoxantrone, etoposide, cytarabine)
EXPERIMENTALPatients receive peposertib PO BID on days 2-21, mitoxantrone IV over 15 minutes, etoposide IV over 60 minutes and cytarabine IV over 60 minutes on days 1-5 in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo ECHO or MUGA during baseline, and blood collection and bone marrow biopsy throughout the study.
Interventions
Undergo bone marrow biopsy
Given IV
Undergo ECHO
Given IV
Given IV
Undergo MUGA
Given PO
Undergo blood sample collection
Eligibility Criteria
You may qualify if:
- An established and confirmed diagnosis of AML by World Health Organization criteria, excluding acute promyelocytic leukemia (APL) (with promyelocytic leukemia -retinoic acid receptor alpha \[PML-RARA\])
- Patients with R/R AML, defined as:
- Relapsed: \>= 5% bone marrow blasts by morphology, reappearance of peripheral blood blasts, or development of extramedullary leukemia after achieving prior CR or CRi. First or second relapse is eligible. First relapse is restricted to participants with CR 1 duration of less than 9-12 months
- Refractory: no CR or CRi after one or more cycles of induction. Induction cycles include regimens with the intent to achieve remission and can include high intensity and/or low intensity regimens
- Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of M3814 in combination with mitoxantrone, etoposide, and cytarabine in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (or Karnofsky \>= 60%)
- Serum bilirubin =\< 1.5 institutional upper limit of normal (ULN) (For patients with hemolysis, Gilbert's syndrome or liver infiltration with leukemia, serum bilirubin =\< 3 x institutional ULN)
- Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN (For patients with liver infiltration with leukemia, AST\[SGOT\]/ALT\[SGPT\] =\< 5 x institutional ULN)
- Glomerular filtration rate (GFR) \>= 60 mL/min/1.73 m\^2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
- Patients must be medically eligible to receive MEC, including acceptable pre-study cardiac function (left ventricular ejection fraction of \>= 45%) and lifetime anthracycline exposure (=\< 360 mg/m\^2 daunorubicin equivalents)
- Patients may have had prior allogeneic hematopoietic cell transplant at least 3 months prior to enrollment but should not have evidence of active graft versus host disease or require systemic immune suppression
- Patients must be willing to submit the blood sampling and bone marrow sampling for any mandatory PK and pharmacodynamics analyses and exploratory biomarkers
- Female patients with child bearing potential must have a negative serum pregnancy test within 72 hours prior to the first study drug administration and all patients must be willing to use effective methods of contraception during the treatment period and 3 months after study completion
- Human immunodeficiency virus (HIV)-infected patients will be eligible for this trial if they are on effective antiretroviral regimens utilizing non-CYP-interacting agents, they have an undetectable viral load, they have a CD4 count \> 350 cells/mm\^3, and they have no history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections. If there is evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy, if indicated. If there is history of hepatitis C virus (HCV) infection, the patient must have been treated and have undetectable HCV viral load
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- +2 more criteria
You may not qualify if:
- Patients must not have had prior treatment with MEC
- Patients must not have documented active central nervous system (CNS) involvement by leukemia. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events (AEs)
- Patients must not have received any other investigational or commercial agents or therapies administered with the intention to treat their leukemia within 14 days or 5 elimination half-lives (whichever is shorter) of first receipt of study drug, with the exception of hydroxyurea and/or leukapheresis used to control white blood cell counts
- Patients who cannot discontinue concomitant medications or herbal supplements that are strong inhibitors or strong inducers of cytochrome P450 (CYP) isoenzymes CYP3A4/5, CYP2C9 and CYP2C19 during treatment with M3814. Concomitant use of CYP1A2, CYP2B6 and CYP3A4/5 substrates with a narrow therapeutic index are also excluded during treatment with M3814. Patients may confer with the study doctor to determine if alternative medications can be used. The following categories of medications and herbal supplements must be discontinued for at least the specified period of time prior to the first dose of M3814:
- Strong inducers of CYP3A4/5, CYP2C9 and CYP2C19: \>= 3 weeks or 5 elimination half-lives (whichever is shorter) prior to the first dose of M3814
- Strong inhibitors of CYP3A4/5, CYP2C9 and CYP2C19: \>= 1 week or 5 elimination half-lives (whichever is shorter) prior to the first dose of M3814
- Substrates of CYP1A2, CYP2B6 and CYP3A4/5 with a narrow therapeutic index: \>= 1 day prior to the first dose of M3814
- Concomitant use of histamine-2 (H2)-blockers or proton pump inhibitors should be avoided as these might affect absorption of M3814; administrations have to be discontinued at least 5 days or 5 elimination half-lives (whichever is shorter) prior to the first dose of M3814. Antacid drugs should not be taken 1 hour before and until 2 hours after M3814 administration
- Patients receiving sorivudine or any chemically related analogues (such as brivudine) are excluded
- Patients who require oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes (including coumadin and warfarin), or who received such agents within 5 days or 5 elimination half-lives (whichever is shorter) of the first dose of M3814. Low and high-molecular weight heparins are permitted provided the platelets are maintained at greater than 30,000/mm\^3
- Patients with ongoing active infection or who have received a live attenuated vaccine within 30 days of dosing with M3814
- Patients must not have known significant cardiopulmonary disease defined as:
- Unstable angina;
- Congestive heart failure (New York Heart Association \[NYHA\] class III or IV);
- Myocardial infarction (MI) within 6 months prior to first dose. Patients who had ischemic heart disease such as acute coronary syndrome (ACS), MI, and/or revascularization more than 6 months before screening and who are without cardiac symptoms or those with a prior non-ST elevation MI (NSTEM) due to demand-supply mismatch (NSTEM Type II) may enroll
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (15)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
USC Norris Oncology/Hematology-Newport Beach
Newport Beach, California, 92663, United States
Keck Medical Center of USC Pasadena
Pasadena, California, 91105, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Mount Sinai Hospital
New York, New York, 10029, United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219, United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Brian A Jonas
City of Hope Comprehensive Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 10, 2019
First Posted
June 12, 2019
Study Start
May 5, 2020
Primary Completion (Estimated)
June 30, 2026
Study Completion (Estimated)
June 30, 2026
Last Updated
April 13, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.