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

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ClinicalTrials.gov Identifier: NCT03315039
Recruitment Status : Recruiting
First Posted : October 19, 2017
Last Update Posted : December 10, 2018
Sponsor:
Information provided by (Responsible Party):
Moleculin Biotech, Inc.

Tracking Information
First Submitted Date  ICMJE October 16, 2017
First Posted Date  ICMJE October 19, 2017
Last Update Posted Date December 10, 2018
Actual Study Start Date  ICMJE March 28, 2018
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History Complete list of historical versions of study NCT03315039 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Liposomal Annamycin for the Treatment of Subjects With Acute Myeloid Leukemia (AML)
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leukemia, Myeloid, Acute
Intervention  ICMJE 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  ICMJE Experimental: Liposomal annamycin
Intervention: Drug: Liposomal Annamycin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 18, 2017)
33
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2019
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Robert Shepard, MD 919-271-3805 ShepardRobert@hotmail.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03315039
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: Undecided
Responsible Party Moleculin Biotech, Inc.
Study Sponsor  ICMJE Moleculin Biotech, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Robert Shepard, MD Moleculin Biotech, Inc.
PRS Account Moleculin Biotech, Inc.
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP