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Trial record 1 of 5 for:    annamycin
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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.
 
ClinicalTrials.gov Identifier: NCT03388749
Recruitment Status : Recruiting
First Posted : January 3, 2018
Last Update Posted : June 25, 2020
Sponsor:
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 has relapsed after standard induction therapy

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

Detailed Description:

Enrollment will occur in cohorts of 3 subjects in a conventional 3+3 escalating dose design, starting at a dose level of 120 mg/m2/day administered for 3 days. Dose escalation will take place on the basis of safety assessments in sequential cohorts of 3 subjects each. The initial cohort will receive 120 mg/m2/day for 3 days. For Cohorts 1, 2, 3, 4, and 5, dose escalation will occur in 30-mg/m2/day increments until subjects are enrolled at a 240-mg/m2/day dose. For Cohorts 6, 7, and 8, dose escalation will occur in 60-mg/m2/day increments until subjects are enrolled at a maximum dose of 420 mg/m2/day. Thus subsequent cohorts will receive 150, 180, 210, 240, 300, 360, and up to a maximum of 420 mg/m2/day for 3 days in the absence of safety concerns.

In each cohort during the dose escalation phase, if 1 of the 3 subjects experiences a DLT, the cohort of subjects at that dose level will be expanded to 6 subjects. If at least 2 of the 6 subjects experience a DLT, this will be considered a toxic dose and the next 3 subjects will be treated at a lower dose. The dose will be de-escalated in 30-mg/m2/day increments. As such, if at least 2 out of 6 subjects receiving 300, 360, or 420 mg/m2/day experience a DLT, the next 3 subjects will receive 270, 330, or 390 mg/m2/day, respectively. The MTD is defined as the highest dose of L-Annamycin at which fewer than 2 (of a cohort of up to 6) subjects experience a DLT.

Once the MTD/RP2D is identified, up to 21 additional subjects will be enrolled at the MTD/RP2D to better define toxicity and evaluate efficacy at this dose.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 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 Has Relapsed After Standard Induction Therapy
Actual Study Start Date : December 17, 2018
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : December 2021


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. Evaluation of safety and identification of the MTD/RP2D for L-Annamycin [ Time Frame: Day 1 through Day 28 ]
    The number of patients who experience dose-limiting toxicities (DLT) will be captured at each dose level of L-Annamycin in order to determine the MTD/RP2D


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: Between Day 15 and Day 35 (+/- 3 days) ]
    Determined by acute myeloid leukemia (AML) response rate based on the International Working Group (IWG) Response Criteria in AML (Cheson, 2003). Leukemia response rate will be evaluated by the investigator at the end of each L-Annamycin cycle based on bone marrow aspirate and peripheral blood evaluations.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria

  1. Subjects have a pathologically confirmed diagnosis of AML by World Health Organization classification.
  2. Subjects have AML that has relapsed after standard induction therapy (i.e., subjects relapsed after experiencing a CR with their prior therapy). To be defined as relapse, there must be >5% blasts in the bone marrow.
  3. For the expansion phase only, the subjects' AML must have relapsed after first-line therapy that included an anthracycline.
  4. Subjects are age ≥18 years at the time of signing informed consent.
  5. Subjects have not received chemotherapy, radiation, or major surgery within 2 weeks prior to first dose of study drug and/or have recovered from the toxic side effects of any previous therapy, unless treatment is indicated as a result of progressive disease, such as hydroxyurea.
  6. Subjects have not received investigational therapy within 4 weeks of the first dose of study drug.
  7. Subjects have an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
  8. Subjects have adequate laboratory results including the following:

    1. Bilirubin ≤2 times the upper limit of normal unless due to Gilbert Syndrome or leukemic infiltration of the liver
    2. Alanine aminotransferase (serum glutamic pyruvic transaminase), aspartate aminotransferase (serum glutamic-oxaloacetic transaminase), and alkaline phosphatase <3 times the upper limit of normal unless due to organ involvement.
    3. Adequate renal function with creatinine levels ≤2 times the upper limit of normal.
  9. Subjects 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 2 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 have been diagnosed with acute promyelocytic leukemia or have primarily refractory AML.
  2. The subjects are receiving concomitant therapy that includes other chemotherapy that is or may be active against AML, except for hydroxyurea, up to Day 1 of L-Annamycin administration.
  3. Subjects have any condition that, in the opinion of the Investigator, places the subject at unacceptable risk if they were to participate in the study.
  4. Subjects have central nervous system involvement.
  5. Subjects have left ventricular ejection fraction (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, subjects with a history of additional risk factors for torsade des pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome), and subjects who use concomitant medications that significantly prolong the QT/QTc interval.
  6. Subjects have 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.
  7. Subjects are pregnant, lactating, or not using adequate contraception.
  8. Subjects have a known allergy to anthracyclines.
  9. Subjects have ongoing Grade 1 mucositis at the time of entry.
  10. Subjects are required to use strong inhibitors and inducers of Cytochrome P450 family of enzymes (CYP) and transporters that cannot be held during treatment days.

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 ClinicalTrials.gov identifier (NCT number): NCT03388749


Contacts
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Contact: Robert Shepard, MD 919-271-3805 rshepard@moleculin.com
Contact: Cynthia Abbate cabbate@moleculin.com

Locations
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Poland
Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego Recruiting
Poznań, Poland
Contact: Lidia Gil, MD, PhD         
Contact: Agnieszka Nowak-Potoczek    +48 669 349 039      
Instytut Hematologii i Transfuzjologii, Klinika Hematologii Recruiting
Warszawa, Poland, 02-776
Contact: Monika Jusko       mjusko@ihit.waw.pl   
Principal Investigator: Ewa Lech-Maranda         
Samodzielny Szpital Kliniczny nr 1 Recruiting
Wrocław, Poland, 50-367
Contact: Tomasz Wrobel, MD, PhD         
Contact: Paula Jablonowska    +48 533 193 182      
Medical University of Lodz Recruiting
Łódź, Poland, 93-510
Contact: Agnieszka Wierznowska, MD, PhD         
Contact: Marta Robak       marta.zubkowicz@gmail.com   
Sponsors and Collaborators
Moleculin Biotech, Inc.
Investigators
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Study Director: Robert Shepard, MD Moleculin Biotech, Inc.
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Responsible Party: Moleculin Biotech, Inc.
ClinicalTrials.gov Identifier: NCT03388749    
Other Study ID Numbers: MB-105
First Posted: January 3, 2018    Key Record Dates
Last Update Posted: June 25, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Annamycin
Antibiotics, Antineoplastic
Antineoplastic Agents