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

• Sponsor: Moleculin Biotech, Inc.
• Information provided by (Responsible Party): Moleculin Biotech, Inc.

Tracking Information

• First Submitted Date: October 16, 2017
• First Posted Date: October 19, 2017
• Last Update Posted Date: December 10, 2018
• Actual Study Start Date: March 28, 2018
• Estimated Primary Completion Date: July 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 18, 2017)

Dose-limiting Toxicity [ Time Frame: Day 21 ]

Number of patients with a dose-limiting toxicity (DLT) at each dose evaluated

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03315039 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: October 18, 2017)

• 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
• 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)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Leukemia, Myeloid, Acute

Intervention

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).

Study Arms

Experimental: Liposomal annamycin

Intervention: Drug: Liposomal Annamycin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 18, 2017): 33
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2019
• Estimated Primary Completion Date: July 2019 (Final data collection date for primary outcome measure)

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 550 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Robert Shepard, MD; 919-271-3805; ShepardRobert@hotmail.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03315039
• Other Study ID Numbers: MB-104
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Moleculin Biotech, Inc.
• Study Sponsor: Moleculin Biotech, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Robert Shepard, MD; Moleculin Biotech, Inc.

• PRS Account: Moleculin Biotech, Inc.
• Verification Date: December 2018