A clinical study conducted to evaluate the safety, efficacy and tolerability of a drug called liposomal annamycin administered with cytarabine, in patients with acute myeloid leukemia.

Phase 1/2

Active, not recruiting

• Conditions: Acute Myeloid Leukemia

• Registration Number: 2024-516388-10-00
• Lead Sponsor: Moleculin Biotech Inc.

Brief Summary

Evaluate the safety and identify the maximum tolerated dose (MTD)/Recommended Phase 2 Dose (RP2D) of liposomal annamycin (LAnnamycin in combination with a standard regimen of cytarabine (Ara-C, cytosine arabinoside) for the treatment of subjects with AML as firs line therapy or in subjects who are refractory to or relapsed after induction therapy.

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-08-26
• Last Update Posted: 2025-03-16

Recruitment & Eligibility

• Status: Ongoing, recruitment ended
• Sex: Not specified
• Target Recruitment: 24

Inclusion Criteria

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.

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. a. Sexually active, fertile women must use effective forms of contraception (e.g., complete abstinence, intrauterine device, oral contraceptive) from the time of informed consent until at least 6 months after discontinuing study drug. b. Sexually active men must use effective contraceptive methods from the time of subject informed consent until at least 3 months after discontinuing study drug.

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 firstsecond- 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: a. Bilirubin ≤2 times the upper limit of normal unless due to Gilbert Syndrome or leukemic infiltration of the liver. b. Serum glutamic-oxaloacetic transaminase (SGOT), serum glutamicpyruvic transaminase (SGPT), and alkaline phosphatase <2.5 times the upper limit of normal unless due to organ involvement. c. 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.

Exclusion Criteria

The subject was diagnosed with acute promyelocytic leukemia.

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. (Appendix E)

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 LAnnamycin 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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		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
CRi: CR with incomplete recovery of platelets and/or neutrophils		CRi: CR with incomplete recovery of platelets and/or neutrophils
PR: a ≥50% decrease in marrow blasts		PR: a ≥50% decrease in marrow blasts
Subject deemed eligible for hematopoietic stem cell transplantation		Subject deemed eligible for hematopoietic stem cell transplantation

Trial Locations

Locations (9)

Instytut Hematologii I Transfuzjologii; 🇵🇱 Warsaw, Poland

Szpital Kliniczny im. H. Święcickiego Uniwersytetu Medycznego im. K. Marcinkowskiego w Poznaniu; 🇵🇱 Poznań, Poland

Uniwersyteckie Centrum Kliniczne; 🇵🇱 Gdansk, Poland

Dolnośląskie Centrum Onkologii, Pulmonologii i Hematologii; 🇵🇱 Wrocław, Poland

Samodzielny Publiczny Szpital Kliniczny Nr 1 im. prof. T. Sokołowskiego Pomorskiego UM; 🇵🇱 Szczecin, Poland

SP ZOZ MSWiA z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie; 🇵🇱 Olsztyn, Poland

Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori (IRST) IRCCS; 🇮🇹 Meldola, Italy

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”; 🇮🇹 Bologna, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS; 🇮🇹 Roma, Italy

Instytut Hematologii I Transfuzjologii

🇵🇱Warsaw, Poland

Ewa Lech-Maranda

Site contact

48223496334

emaranda@ihit.waw.pl