Leukemia, Myeloid, AcutePhase 1/2NCT03315039
Study of Liposomal Annamycin for the Treatment of Subjects With Acute Myeloid Leukemia (AML)
A Phase 1/2 study testing Liposomal Annamycin in people with Leukemia, Myeloid, Acute, run by Moleculin Biotech, Inc. at 4 sites in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myeloid, Acute
- What is being tested?
- Liposomal Annamycin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 4 sitesUnited States
- Study dates
- 28 Mar 2018to 20 Jun 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A pathologically confirmed diagnosis of AML by World Health Organization (WHO) classification.
- AML that is refractory to or relapsed after standard induction therapy.
- Age ≥18 years at the time of signing informed consent.
- 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.
- No investigational therapy within four weeks of the first dose of study drug.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
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- Adequate laboratory results including the following:
- Bilirubin ≤1.5 times the upper limit of normal (ULN) unless due to Gilbert Syndrome
- Serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT) and alkaline phosphatase <3 times the ULN) unless due to organ involvement
- 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.)
- Prior anthracycline cumulative dose below 551 mg/m2 or the daunorubicin equivalent which is the recommended non-cardiotoxic level.
- 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.
- Women of childbearing potential must have a negative serum or urine pregnancy test.
- 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.
- 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
- 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
Who cannot join
- Subjects diagnosed with Acute Promyelocytic Leukemia.
- 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.
- Prior mediastinal radiotherapy
- Any condition which, in the opinion of the Investigator, places the subject at unacceptable risk if he/she were to participate in the study.
- 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.
- 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.
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- Pregnant, lactating, or not using adequate contraception.
- Known allergy to anthracyclines.
- Any evidence of mucositis/stomatitis or previous history of severe (≥Grade 3) mucositis from prior therapy.
- Required use of strong inhibitors and inducers of CYP enzymes and transporters.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
University of Florida
Gainesville, Florida, 32610
UC San Diego Health
La Jolla, California, 92093
Southwest Cancer Center
Lubbock, Texas, 79415
About this study
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
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
- Conditions
- Leukemia, Myeloid, Acute
- Being tested
- Liposomal Annamycin
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liposomal AnnamycinDrug
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 group | Role | What they receive |
|---|---|---|
| Liposomal annamycin | Experimental | 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). Receives: Drug: Liposomal Annamycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting Toxicity
Number of patients with a dose-limiting toxicity (DLT) at each dose evaluated
Measured: Day 28
Secondary outcomes (2)
Pharmacokinetics - Area Under the Plasma Concentration
Area under the plasma concentration - time curve (AUC) of annamycin and its metabolite, annamycinol
Measured: 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
Number of Participants With Anti-leukemic Activity
Determined by acute myeloid leukemia (AML) response rate based on the International Working Group (IWG) Response Criteria in AML (Cheson, 2003). Anti-leukemic Activity measured by bone marrow biopsy/aspirate pre and post treatment.
Measured: 15-35 Days after the start of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2017
- Study start28 Mar 2018
- Primary completion14 Jan 2020
- Study completion20 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Moleculin Biotech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Robert Shepard, MD, Study director, Moleculin Biotech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03315039
- Sponsor's protocol ID
- MB-104
- Status last verified
- Feb 2022
- First submitted
- 16 Oct 2017
- Last updated
- 10 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03315039
- Acronym / sponsor ID
- MB-104
- Conditions
- Leukemia, Myeloid, Acute
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Moleculin Biotech, Inc.Industry (pharma, biotech, devices)
- Study start
- 28 Mar 2018 (actual)
- Primary completion
- 14 Jan 2020 (actual)
- Study completion
- 20 Jun 2020 (actual)
- First posted
- 19 Oct 2017 (actual)
- Results
- Posted 23 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Liposomal annamycin | Experimental | Drug: Liposomal Annamycin2-hour intravenous infusion liposomal annamycin daily for 3 consecutive days followed by 18 days off study drug (i.e., one treatment cycle = 21 days). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- A pathologically confirmed diagnosis of AML by World Health Organization (WHO) classification.
- AML that is refractory to or relapsed after standard induction therapy.
- Age ≥18 years at the time of signing informed consent.
- 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.
- No investigational therapy within four weeks of the first dose of study drug.
Key exclusion criteria (10 listed)
- Subjects diagnosed with Acute Promyelocytic Leukemia.
- 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.
- Prior mediastinal radiotherapy
- Any condition which, in the opinion of the Investigator, places the subject at unacceptable risk if he/she were to participate in the study.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liposomal Annamycin2-hour intravenous infusion liposomal annamycin daily for 3 consecutive days followed by 18 days off study drug (i.e., one treatment cycle = 21 days). | Drug | Liposomal annamycin |
Primary outcome
Dose-limiting Toxicity
Time frame: Day 28
Number of patients with a dose-limiting toxicity (DLT) at each dose evaluated
2 secondary outcomes
Pharmacokinetics - Area Under the Plasma Concentration
Time frame: 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
Number of Participants With Anti-leukemic Activity
Time frame: 15-35 Days after the start of therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Shepard, MD study director
Moleculin Biotech, Inc.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Liposomal Annamycin in people with Leukemia, Myeloid, Acute, run by Moleculin Biotech, Inc. at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting Toxicity (time frame: Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2022.