Clinical trial NCT03315039: Study of Liposomal Annamycin for the Treatment of Subjects With Acute Myeloid Leukemia (AML)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Leukemia, Myeloid, Acute
Lead sponsor: Moleculin Biotech, Inc.
Sponsor class: INDUSTRY
First posted: 2017-10-19
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility criteria: 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 below 551 mg/m2 or the daunorubicin equivalent which is the recommended non-cardiotoxic level.
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, (see Table 1). 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.

Primary outcomes:
measure: Dose-limiting Toxicity
timeFrame: Day 28
Secondary outcomes:
measure: Pharmacokinetics - Area Under the Plasma Concentration
timeFrame: Pre-dose and at 0.25, 0.5, 1, 2, 4, 8, and 24 hours after the start of liposomal annamycin infusion on Day 1 and Day 3
measure: Number of Participants With Anti-leukemic Activity
timeFrame: 15-35 Days after the start of therapy
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Health
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Lubbock
country: United States
facility: Southwest Cancer Center
state: Texas
Study officials:
affiliation: Moleculin Biotech, Inc.
name: Robert Shepard, MD
role: STUDY_DIRECTOR
References: