Study of Liposomal Annamycin in Combination With Cytarabine for the Treatment of Subjects With Acute Myeloid Leukemia (AML)

NCT05319587 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: MB-1062020-005493-10
• Study Type: interventional
• Target: 22
• Locations: 2 countries
• Sites: 9

Brief Summary

This is a Phase 1/2, multicenter, open-label, dose-escalation study that will determine the MTD and RP2D of L-Annamycin in combination with cytarabine for the treatment of subjects with AML.

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (1)

• Evaluate the safety and identify the MTD/RP2D of L-Annamycin in combination with a standard regimen of cytarabine (Ara-C, cytosine arabinoside)

  The number of patients who experience dose-limiting toxicities (DLT) will be captured at each dose level of LAnnamycin in order to determine the MTD/RP2D

  Day 1 through Day 28

Secondary Outcomes (2)

• Pharmacokinetics - Area under the plasma concentration

  Pre-dose and at 0.25, 0.5, 1, 2, 4, 8,12 and 24 hours after the start of liposomal annamycin infusion on Day 1 and Day 3

• Anti-leukemic activity

  15-35 Days after the start of therapy

Study Arms (1)

Liposomal annamycin

EXPERIMENTAL

Drug: Liposomal Annamycin; Drug: Cytarabine

Interventions

Liposomal Annamycin DRUG

2-hour intravenous infusion liposomal annamycin daily for 3 consecutive days followed by 18 days off study drug (i.e., one treatment cycle = 21 days).

Liposomal annamycin

Cytarabine DRUG

Administered during cycle 1 at a dose of 2.0 g/m2/day by 4 hours IV infusion for 5 consecutive days and this dose will remain constant for all cohorts, including the expansion phase.

Liposomal annamycin

Eligibility Criteria

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

You may qualify if:

• The subject has a pathologically confirmed diagnosis of AML by World Health Organization classification. This must be in the form of either a bone marrow aspirate or biopsy or a CBC that demonstrates \>5% myeloblasts.
• The subject has AML and has not received prior therapy or is refractory to or relapsed after induction therapy. To be defined as relapse, there must be \>5% blasts in the bone marrow.
• For the expansion phase only (i.e., after the MTD/RP2D is established), subjects must be treated with L-Annamycin as first- second- or third-line therapy (i.e., subjects will not have received more than two prior therapies).
• The subject is age ≥18 years at the time of signing informed consent.
• The subject has received no chemotherapy, radiation, or major surgery within 2 weeks prior to first dose of study drug and/or has recovered from the toxic side effects of that therapy unless treatment is indicated as a result of progressive disease, such as hydroxyurea.
• The subject has received no investigational therapy within 4 weeks of the first dose of study drug.
• The subject has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• The subject has adequate laboratory results including the following:
• Bilirubin ≤2 times the upper limit of normal unless due to Gilbert Syndrome or leukemic infiltration of the liver.
• Serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), and alkaline phosphatase \<2.5 times the upper limit of normal unless due to organ involvement.
• Adequate renal function with creatinine levels ≤2 times the upper limit of normal.
• The subject can understand and sign the informed consent document, can communicate with the Investigator, and can understand and comply with the requirements of the protocol.
• Women of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin test within 72 hours prior to first dose of study drug to rule out pregnancy.
• All men and women must agree to practice effective contraception during the entire study period and after discontinuing study drug, unless documentation of infertility exists.
• Sexually active, fertile women must use 2 effective forms of contraception (abstinence, intrauterine device, oral contraceptive, or double barrier device) from the time of informed consent until at least 6 months after discontinuing study drug.

You may not qualify if:

• The subject was diagnosed with acute promyelocytic leukemia.
• The subject is receiving concomitant therapy that includes other chemotherapy that is or may be active against AML except for agents such as hydroxyurea, just to control the WBC count until chemotherapy or prophylaxis and/or treatment of opportunistic or other infection with antibiotics, antifungals, and/or antiviral agents, including therapy for meningeal disease (i.e., intrathecal chemotherapy), supportive measures, and medications as per standard of care up to Day 1 of L-Annamycin administration.
• The subject received prior mediastinal radiotherapy.
• The subject has central nervous system involvement.
• The subject has any condition that, in the opinion of the Investigator, places the subject at unacceptable risk if he/she were to participate in the study.
• The subject has an LVEF \<50%, valvular heart disease, or severe hypertension. Cardiac subjects with a New York Heart Association classification of 3 or 4 will be excluded. (Cardiology consultation should be requested if any question arises about cardiac function). This also includes subjects with baseline QT/QTc interval \>480 msec, a history of additional risk factors for torsade des pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome), and use of concomitant medications that significantly prolong the QT/QTc interval.
• The subject has 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.
• a. Subjects with a documented COVID diagnosis within 14 days of screening must have a documented negative PCR test and remain asymptomatic for 14 days from that test result before starting study medication.
• The subject is pregnant, lactating, or not using adequate contraception.
• The subject has a known allergy to anthracyclines and/or hypersensitivity to cytarabine, its excipients, or to any contrast media needed for imaging required per protocol.
• The subject has any evidence of mucositis/stomatitis at the time of study entry or previous history of severe (≥Grade 3) mucositis from prior therapy.
• The subject is 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

Sponsors & Collaborators

• Moleculin Biotech, Inc.: lead

Study Sites (9)

Istituto Scientifico Romagolo per lo studio dei umori "Dino Amadori" (IRST) - IRCCS

Meldola, FC, 47014, Italy

Location

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Bologna, 40138, Italy

Location

Fondazione Policlinico Universitario A. Gemelli IRCCS

Roma, Italy

Location

Uniwersytecki Szpital Kliniczny Klinika Hematologii Nowotworow

Wroclaw, Dolnośląskie Województwo, 50-367, Poland

Location

SP ZOZ MsWiA z Warminsko-Mazurksim Centrum Onkologii w Olsztynie Oddzial Kliniczny Hematologii

Olsztyn, Warmian-Masurian Voivodeship, 10-228, Poland

Location

Apteka Szpitalna

Gdansk, Poland

Location

Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego

Poznan, Poland

Location

Samodzielny Publiczny Szpital Kliniczny nr 1 im. Prof. Tadeusza Sokołowskiego w Szczecinie, Klinika Hematologii z Oddziałem Transplantacji Szpiku, Szczecin

Szczecin, Poland

Location

Instytut Hematologii i Transfuzjologii, Klinika Hematologii, Warsaw

Warsaw, Poland

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cytarabine

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

Study Officials

• Wolfram Dempke, MD, PhD

  Moleculin Biotech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2022
• First Posted: April 8, 2022
• Study Start: September 29, 2022
• Primary Completion: August 2, 2023
• Study Completion: August 10, 2023
• Last Updated: September 30, 2025

Record last verified: 2025-09

Locations

IT (3); PL (6)