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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03388749
Recruitment Status : Not yet recruiting
First Posted : January 3, 2018
Last Update Posted : June 25, 2018
Information provided by (Responsible Party):
Moleculin Biotech, Inc.

Brief Summary:
This is a multi-center, open-label, dose escalation study that will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of liposomal annamycin as a single agent for the treatment of subjects with AML that is refractory to or relapsed after standard induction therapy

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Drug: Liposomal Annamycin Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 57 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2 Study of Liposomal Annamycin for the Treatment of Subjects With Acute Myeloid Leukemia (AML) That is Refractory to or Relapsed After Standard Induction Therapy
Estimated Study Start Date : August 2018
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019

Arm Intervention/treatment
Experimental: Liposomal annamycin Drug: Liposomal Annamycin
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).

Primary Outcome Measures :
  1. Dose-limiting Toxicity [ Time Frame: Day 21 ]
    Number of patients with a dose-limiting toxicity (DLT) at each dose evaluated

Secondary Outcome Measures :
  1. Pharmacokinetics - Area under the plasma concentration [ Time Frame: Day 1 and Day 3 ]
    Area under the plasma concentration - time curve (AUC) of annamycin and its metabolite, annamycinol

  2. Anti-leukemic activity [ Time Frame: Day 21] ]
    Determined by acute myeloid leukemia (AML) response rate based on the International Working Group (IWG) Response Criteria in AML (Cheson, 2003)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. A pathologically confirmed diagnosis of AML by World Health Organization (WHO) classification.
  2. AML that is refractory to or relapsed after standard induction therapy.
  3. Age ≥18 years at the time of signing informed consent.
  4. No chemotherapy, radiation, or major surgery within two weeks prior to first dose of study drug and/or recovered from the toxic side effects of that therapy, unless treatment is indicated due to progressive disease.
  5. No investigational therapy within four weeks of the first dose of study drug.
  6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
  7. Adequate laboratory results including the following:

    1. Bilirubin ≤1.5 times the upper limit of normal (ULN) unless due to Gilbert Syndrome
    2. Serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT) and alkaline phosphatase <3 times the ULN) unless due to organ involvement
    3. Adequate renal function (The Cockcroft-Gault equation will be used to estimate creatinine clearance. This equation is as follows: Creatinine clearance in ml/min = (140 - age) x body weight (kg)/72 x plasma creatinine (mg/dL); multiplied by 0.85 for women. Using this equation, adequate renal function will be deemed to be a creatinine clearance of greater than 60 ml/minute.)
  8. Prior anthracycline cumulative dose <50% below recommended non-cardiotoxic levels
  9. 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 pregnancy test.
  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.

    1. Sexually active, fertile women must use two effective forms of contraception (abstinence, intrauterine device, oral contraceptive, or double barrier device) from the time of informed consent and until at least 6 months after discontinuing study drug
    2. Sexually active men and their sexual partners must use effective contraceptive methods from the time of subject informed consent and until at least 3 months after discontinuing study drug

Exclusion Criteria:

  1. Subjects diagnosed with Acute Promyelocytic Leukemia.
  2. Concomitant therapy that includes other chemotherapy that is or may be active against AML except for prophylaxis and/or treatment of opportunistic or other infection with antibiotics, antifungals and/or antiviral agents.
  3. Prior mediastinal radiotherapy
  4. Any condition which, in the opinion of the Investigator, places the subject at unacceptable risk if he/she were to participate in the study.
  5. Positive risk assessment for cardiovascular disease including prior anthracycline cumulative dose more than 50% above recommended non-cardiotoxic levels, left ventricular ejection fraction (LVEF) <50%, valvular heart disease, or severe hypertension. Cardiac subjects with a New York Heart Association (NYHA) 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 TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) and using concomitant medications that significantly prolong the QT/QTc interval.
  6. Clinically relevant serious co-morbid medical conditions including, but not limited to, active infection, recent (less than or equal to six months) myocardial infarction, unstable angina, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled cardiac arrhythmias, chronic obstructive or chronic restrictive pulmonary disease, active CNS disease uncontrolled by standard of care, known positive status for human immunodeficiency virus (HIV) and/or active hepatitis B or C, cirrhosis, or psychiatric illness/social situations that would limit compliance with study requirements.
  7. Pregnant, lactating, or not using adequate contraception.
  8. Known allergy to anthracyclines.
  9. Any evidence of mucositis/stomatitis or previous history of severe (≥Grade 3) mucositis from prior therapy.
  10. Required use of strong inhibitors and inducers of CYP enzymes and transporters.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03388749

Contact: Robert Shepard, MD 919-271-3805

Sponsors and Collaborators
Moleculin Biotech, Inc.
Study Director: Robert Shepard, MD Moleculin Biotech, Inc.

Responsible Party: Moleculin Biotech, Inc. Identifier: NCT03388749     History of Changes
Other Study ID Numbers: MB-105
First Posted: January 3, 2018    Key Record Dates
Last Update Posted: June 25, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action