L-Annamycin for Injection in Combination With Cytarabine Injection as Second Line Therapy for Remission Induction in Adult Subjects With Refractory/Relapsed AML

NCT06788756 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: MB-1082024-518359-47-00
• Study Type: interventional
• Target: 312
• Locations: 8 countries
• Sites: 25

Brief Summary

This pivotal phase 2/3, multi-center, adaptive design study of L-Annamycin for Injection in combination with Cytarabine Injection as second line therapy for remission induction in adult subjects with refractory/relapsed AML is divided into two parts, Part A and Part B.

Conditions

Acute Myeloid Leukaemia (AML)

Outcome Measures

Primary Outcomes (2)

• Part A -Determination of Optimal Dosage Regimen

  1\. To identify the optimal dosage regimen of L Annamycin for Injection (190 versus 230 mg/m2/day) in combination with Cytarabine Injection (2.0 g/m2/day) as second line therapy for remission induction in adult subjects with refractory/relapsed acute myeloid leukemia (AML) as measured by rate of complete remission (CR) after one treatment cycle.

  From initiation of the first randomized treatment cycle until the first post treatment bone marrow assessment, assessed up to Day 49

• Part B - Expansion at Optimal Dosage Regimen

  To confirm the superior efficacy of the optimal dosage regimen of L-Annamycin for Injection in combination with Cytarabine Injection (determined in Part A) versus placebo in combination with Cytarabine Injection as second line therapy for remission induction in adult subjects with refractory/relapsed AML as measured by rate of CR after one treatment cycle

  From initiation of the first randomized treatment cycle until the first post treatment bone marrow assessment, assessed up to Day 49

Secondary Outcomes (2)

• Part A -Comparison of Efficacy as Measured by Overall Survival (OS)

  From date of randomization to treatment (Day 1) to the date of death from any cause, assessed up to 2 years after the first dose of randomized study drug

• Part B - Confirmation of Efficacy of the Optimal Dosage Regimen as Measured by Overall Survival (OS)

  From date of randomization to treatment (Day 1) to the date of death from any cause, assessed up to 2 years after the first dose of randomized study drug

Study Arms (5)

Part A / Treatment Arm 1

PLACEBO COMPARATOR

placebo (0.9% Sodium Chloride Injection, i.e., the diluent for L-Annamycin for Injection) for three consecutive days in combination with 2.0 g/m2/day Cytarabine Injection for five consecutive days

Drug: Placebo in combination with Cytarabine Injection

Part A / Treatment Arm 2

ACTIVE COMPARATOR

190 mg/m2/day L-Annamycin for Injection for three consecutive days in combination with 2.0 g/m2/day Cytarabine Injection for five consecutive days.

Drug: Liposomal Annamycin Injection in combination with Cytarabine Injection

Part A / Treatment Arm 3

ACTIVE COMPARATOR

230 mg/m2/day L-Annamycin for Injection for three consecutive days in combination with 2.0 g/m2/day Cytarabine Injection for five consecutive days.

Drug: Liposomal Annamycin Injection in combination with Cytarabine Injection

Part B / Treatment Arm 1

PLACEBO COMPARATOR

Placebo (0.9% Sodium Chloride Injection) for three consecutive days in combination with 2.0 g/m2/day Cytarabine Injection for five consecutive days (i.e., the same as Treatment Arm 1 of Part A).

Drug: Placebo in combination with Cytarabine Injection

Part B / Treatment Arm X

ACTIVE COMPARATOR

Optimal dosage regimen (as determined in Part A) of L Annamycin for Injection (190 mg/m2/day or 230 mg/m2/day) for three consecutive days in combination with 2.0 g/m2/day Cytarabine Injection for five consecutive days (i.e., the same as Treatment Arm 2 or 3, respectively, of Part A).

Drug: Liposomal Annamycin for Injection in combination with Cytarabine Injection.

Interventions

Liposomal Annamycin Injection in combination with Cytarabine Injection DRUG

190 mg/m2/day L-Annamycin for Injection for three consecutive days in combination with 2.0 g/m2/day Cytarabine Injection for five consecutive days.

Part A / Treatment Arm 2

Placebo in combination with Cytarabine Injection DRUG

placebo (0.9% Sodium Chloride Injection, i.e., the diluent for L-Annamycin for Injection) for three consecutive days in combination with 2.0 g/m2/day Cytarabine Injection for five consecutive days.

Part A / Treatment Arm 1; Part B / Treatment Arm 1

Liposomal Annamycin for Injection in combination with Cytarabine Injection. DRUG

optimal dosage regimen (as determined in Part A) of L Annamycin for Injection (190 mg/m2/day or 230 mg/m2/day) for three consecutive days in combination with 2.0 g/m2/day Cytarabine Injection for five consecutive days (i.e., the same as Treatment Arm 2 or 3, respectively, of Part A).

Part B / Treatment Arm X

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a pathologically confirmed diagnosis of AML per the 2022 International Consensus Classification (ICC) as adopted in the European LeukemiaNet (ELN) 2022 recommendations for the diagnosis and management of AML. The tests and procedures used to establish the diagnosis of AML should be consistent with the ELN's 2022 recommendations
• Has refractory/relapsed AML after having received only one prior line of therapy\*.
• \*A prior line of therapy will be defined as the planned therapy consisting of one or more cycles of episodic treatment or a defined period of continuous treatment. This may consist of single-agent or combination therapy as well as a planned sequence of treatment phases. For example, first-line treatment of AML with induction, consolidation, and alloHSCT is considered one line of therapy. A line of therapy ends when the patient fails to achieve a response within a prespecified period (refractory) or relapses after achieving CR. For the purpose of confirming refractory AML at screening, refractory disease will be defined as CR not being achieved after first line therapy \[i.e., after 1 cycle of intensive therapy or 180 days after commencing less-intensive therapy (shorter durations of less-intensive therapy may be considered for refractory disease on a case by case basis after discussion between the PI and Medical Monitor)\].
• Between 18 and 80 years of age (inclusive) at the time of signing the informed consent form (ICF).
• Has received no chemotherapy, radiation, or major surgery within 2 weeks prior to the first randomized dose of study drug or has recovered from the toxic side effects of that therapy. Hydroxyurea to control white blood cell (WBC) count, supportive measures, and prophylaxes as required under the protocol will be allowed. Treatment of opportunistic or other infections with antibiotics, antifungals, and/or antiviral agents, including therapy for meningeal disease (i.e., intrathecal chemotherapy), per institutional standards of care will be allowed during this period, as long as the symptoms of infection have resolved by 1 week prior to the first dose of randomized study drug.
• Has received no investigational therapy within 4 weeks prior to the first randomized dose of study drug.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at screening.
• Has a life expectancy of greater than six weeks at screening.
• Has adequate laboratory results at screening including the following:
• Total bilirubin ≤2.0 times the upper limit of normal (ULN). For subjects with leukemic involvement or Gilbert Syndrome, total bilirubin must be ≤3.0 ULN.
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase \<3.5 times the ULN. For subjects with organ involvement, AST, ALT, and alkaline phosphatase must be ≤4.5 times the ULN.
• Creatinine clearance ≥60 mL/min (using Cockcroft-Gault equation).
• Can understand and sign the ICF, can communicate with the PI, and can understand and comply with the requirements of the protocol.
• For women of childbearing potential (WCBP): Must have a negative serum beta human chorionic gonadotropin (ß-hCG) pregnancy test within 72 hours prior to the first randomized dose of study drug.
• For WCBP: Must agree to not donate ova and use a highly effective method of birth control from the time of informed consent through 6 months after their last randomized dose of study drug.

You may not qualify if:

• Has prior or current diagnosis of acute promyelocytic leukemia (APL) or myelodysplastic syndrome (MDS)/AML
• Received prior mediastinal radiotherapy.
• Has central nervous system involvement.
• Has impaired cardiac function, including any of the following:
• Abnormal LVEF at screening \[per American College of Cardiology, normal LVEF is 50 to 70%
• Valvular heart disease.
• Severe, uncontrolled hypertension.
• Uncontrolled cardiac arrhythmias.
• Recent (≤6 months prior to screening) myocardial infarction.
• Unstable angina.
• Symptomatic congestive heart failure.
• New York Heart Association (NYHA) classification of 3 or 4.
• QT interval/corrected QT (QTc) interval \>480 msec at screening.
• History of additional risk factors for torsade des pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
• Use of concomitant medications with known risk of Torsades de Pointes (TdP) (i.e., drugs that prolong the QT interval and that are clearly associated with a known risk of TdP, even when taken as recommended; refer to Appendix G for examples of such drugs), unless in the clinical judgement of the PI, the medication is imperative and can be used safely with adequate monitoring.

Sponsors & Collaborators

• Moleculin Biotech, Inc.: lead

Study Sites (25)

Bioresearch Partners

Miami, Florida, 33155, United States

RECRUITING

Augusta University - Georgia Cancer Center

Augusta, Georgia, 30912, United States

RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

RECRUITING

Atlantic Health

Morristown, New Jersey, 07960, United States

RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19117, United States

RECRUITING

GEORGIA: LLC ARENSIA Exploratory Medicine

Tbilisi, 0112, Georgia

RECRUITING

Caucasus Medical Center

Tbilisi, 0186, Georgia

RECRUITING

RCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia

Bologna, 40138, Italy

RECRUITING

AOU Careggi

Florence, 50134, Italy

RECRUITING

AUSL della Romagna - Santa Maria delle Croci - Ravenna

Ravenna, 48121, Italy

RECRUITING

Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of the Sacred Heart

Roma, 00168, Italy

RECRUITING

LSMU Kauno klinikos

Kaunas, LT-50161, Lithuania

RECRUITING

Szpital Kliniczny MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie Oddział Kliniczny Hematologii i Chorób Wewnętrznych z Ośrodkiem Transplantacji Szpiku

Olsztyn, 10-228, Poland

RECRUITING

Oddział Hematologii i Transplantacji Szpiku, Uniwersytecki Szpital Kliniczny w Poznaniu

Poznan, 60-569, Poland

RECRUITING

Uniwersytecki Szpital Kliniczny Klinika Hematologii i Transplantologii (Szczecin)

Szczecin, 71-252, Poland

RECRUITING

Wojewódzki Szpital Zespolony im. L. Rydygiera w Toruniu, Oddział Hematologii

Torun, 87-100, Poland

RECRUITING

Instytut Hematologii i Transfuzjologii, Klinika Hematologii

Warsaw, 02-776, Poland

RECRUITING

ARENSIA research clinic at the Oncology Institute "Prof. Dr. Ion Chiricuţă"

Cluj-Napoca, 400015, Romania

RECRUITING

Institut Català d'Oncología (ICO) - Hospital Germans Trias i Pujol

Barcelona, Badalona, 08916, Spain

RECRUITING

Hospital Universitario Central de Asturias (HUCA)

Oviedo, Principality of Asturias, 33011, Spain

RECRUITING

Hospital MD Anderson Cancer Center Madrid

Madrid, 28033, Spain

RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Universitario La Fe de Valencia

Valencia, 46026, Spain

RECRUITING

ARENSIA Exploratory Medicine, LLC

Kyiv, 01135, Ukraine

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cytarabine; Injections

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; Drug Administration Routes; Drug Therapy; Therapeutics

Central Study Contacts

Paul Waymack, MD, Sc.D

CONTACT

+1 202-760-1378; pwaymack@moleculin.com

Erikson Wasyl, MS

CONTACT

860-395-9275; ewasyl@moleculin.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2024
• First Posted: January 23, 2025
• Study Start: March 12, 2025
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2030
• Last Updated: April 29, 2026

Record last verified: 2026-04

Locations

ES (5); RO (1); LI (1); PL (5); US (6); GE (2); UA (1); IT (4)