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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Moleculin Biotech Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

23 Sep 2022 → 26 Aug 2025

Decision date (initial)

2024-08-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-516388-10-00

EudraCT number

2020-005493-10

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Safety, Dose response, Pharmacokinetic, Therapy

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.

Conditions and MedDRA coding

Acute Myeloid Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 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.
2. 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.
3. 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).
4. The subject is age ≥18 years at the time of signing informed consent.
5. 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.
6. The subject has received no investigational therapy within 4 weeks of the first dose of study drug.
7. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
8. 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.
9. 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.
10. 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.
11. 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.

Exclusion criteria 11

1. The subject was diagnosed with acute promyelocytic leukemia.
2. 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.
3. The subject received prior mediastinal radiotherapy.
4. The subject has central nervous system involvement.
5. 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.
6. 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.
7. 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.
8. The subject is pregnant, lactating, or not using adequate contraception.
9. 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.
10. 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.
11. 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)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Moleculin Biotech Inc.

Sponsor organisation

Moleculin Biotech Inc.

Address

5300 Memorial Drive Ste 950

City

Houston

Postcode

77007-8274

Country

United States

Scientific contact point

Organisation

Moleculin Biotech Inc.

Contact name

Donald Picker

Public contact point

Organisation

Moleculin Biotech Inc.

Contact name

Donald Picker

Locations

2 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications