Acute Myeloid Leukemia MedDRA version: 21.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: Liposomal annamycin
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: ANNAMYCIN
CAS Number: 92689-49-1
Current Sponsor code: CP 507
Other descriptive name:
Sponsors
Moleculin Biotech, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects have a pathologically confirmed diagnosis of AML by World Health Organization classification. 2. Subjects have AML that is refractory to or relapsed after induction therapy (i.e., subjects relapsed after experiencing a CR with their prior therapy). To be defined as relapse, there must be >5% blasts in the bone marrow. 3. For the expansion phase only (i.e., after the MTD/RP2D is established): a. Subjects with primarily refractory AML must be treated with L-Annamycin as the first therapy following failed induction with or without consolidation (i.e., treatment with L-Annamycin is the second line therapy and the first therapy for primarily refractory AML). b. Subjects with relapsed AML must be treated with L-Annamycin as the first or second therapy following documented relapse (i.e., treatment with L-Annamycin is the second or third line). 4. Subjects are age =18 years at the time of signing informed consent. 5. Subjects have not received chemotherapy, radiation, or major surgery within 2 weeks prior to first dose of study drug and/or have recovered from the toxic side effects of any previous therapy, unless treatment is indicated as a result of progressive disease, such as hydroxyurea. 6. Subjects have not received investigational therapy within 4 weeks of the first dose of study drug. 7. Subjects have an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. 8. Subjects have adequate laboratory results including the following: a. Bilirubin =2 times the upper limit of normal unless due to Gilbert Syndrome or leukemic infiltration of the liver b. Alanine aminotransferase (serum glutamic pyruvic transaminase), aspartate aminotransferase (serum glutamic-oxaloacetic transaminase), and alkaline phosphatase =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Subjects have been diagnosed with acute promyelocytic leukemia or have primarily refractory AML. 2. The subjects are receiving concomitant therapy that includes other chemotherapy that is or may be active against AML, except agents such as hydroxyurea, used to control the WBC count until chemotherapy, to Day 1 of L-Annamycin administration. 3. Subjects have any condition that, in the opinion of the Investigator, places the subject at unacceptable risk if they were to participate in the study. 4. Subjects have central nervous system involvement. 5. Subjects have left ventricular ejection fraction (LVEF) 480 msec, subjects with a history of additional risk factors for torsade des pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome), and subjects who use concomitant medications that significantly prolong the QT/QTc interval. 6. Subjects have clinically relevant serious comorbid medical conditions including, but not limited to, active infection, recent (less than or equal to 6 months) myocardial infarction, unstable angina, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled cardiac arrhythmias, chronic obstructive or chronic restrictive pulmonary disease, known positive status for human immunodeficiency virus and/or active hepatitis B or C, cirrhosis, or psychiatric illness/social situations that would limit compliance with study requirements. 7. Subjects are pregnant, lactating, or not using adequate contraception. 8. Subjects have a known allergy to anthracyclines. 9. Subjects have ongoing Grade 1 mucositis at the time of entry. 10. Subjects are required to use moderate or strong inhibitors and inducers of Cytochrome P450 family of enzymes (CYP) and transporters that cannot be held for 3 days prior to Day 1 and during treatment days.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the safety and identify the recommended Phase 2 dose (RP2D) of liposomal annamycin (L-Annamycin) for the treatment of subjects with AML that is refractory to or relapsed after induction therapy;Secondary Objective: 1. Pharmacokinetics of (L-Annamycin) and its metabolite, annamycinol 2. Preliminary assessment of the antileukemicc activity of L-Annamycin as second line (or subsequent) therapy for subjects with refractory or relapsed AML based on established response criteria, including complete response (CR), CR with incomplete recovery of platelets and/or neutrophils (CRi) partial response (PR), event-free survival (EFS), overall survival (OS), and time to and duration of response ;Primary end point(s): 1. CR: a. Achievement of normal bone marrow morphology on light microscopy with fewer than 5% blasts b. Recovery of peripheral blood counts with an absolute neutrophil count >1.0 × 109/L and platelet counts >100 × 109/L 2. CRi: CR with incomplete recovery of platelets and/or neutrophils 3. PR: a =50% decrease in marrow blasts 4. Subject deemed eligible for hematopoietic stem cell transplantation ;Timepoint(s) of evaluation of this end point: Evaluation at the end of the induction cycle and at the end of the study (EOS). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. EFS: Time from enrollment until disease progression or death from any cause 2. OS: Time from enrollment until death from any cause 3. Time to and duration of response 4. Cytogenetic complete response – cytogenetics normal in those with previously abnormal cytogenetics ;Timepoint(s) of evaluation of this end point: Evaluation at the end of the induction cycle and at the end of the study (EOS). | — |
Countries
Poland
Contacts
Public ContactBozena Sasorska
Theradex Oncology
Outcome results
None listed