- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03388749
Study of Liposomal Annamycin for the Treatment of Subjects With Acute Myeloid Leukemia (AML)
Phase 1/2 Study of Liposomal Annamycin for the Treatment of Subjects With Acute Myeloid Leukemia (AML) That is Refractory to or Relapsed After Induction Therapy
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Poznań, Poland
- Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego
-
Szczecin, Poland, 71-252
- Samodzielny Publiczny Szpital Kliniczny nr 1 im. Prof. Tadeusza Sokołowskiego w Szczecinie, Klinika Hematologii z Oddziałem Transplantacji Szpiku
-
Warszawa, Poland, 02-776
- Instytut Hematologii i Transfuzjologii, Klinika Hematologii
-
Wrocław, Poland, 50-367
- Samodzielny Szpital Kliniczny nr 1
-
Łódź, Poland, 93-510
- Medical University of Lodz
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria
- Subjects have a pathologically confirmed diagnosis of AML by World Health Organization classification.
- Subjects have AML that is refractory to or relapsed after 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.
- Subjects are age ≥18 years at the time of signing informed consent.
- 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.
- Subjects have not received investigational therapy within 4 weeks of the first dose of study drug.
- Subjects have an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
Subjects have adequate laboratory results including the following:
- Bilirubin ≤2 times the upper limit of normal unless due to Gilbert Syndrome or leukemic infiltration of the liver
- Alanine aminotransferase (serum glutamic pyruvic transaminase), aspartate aminotransferase (serum glutamic-oxaloacetic transaminase), and alkaline phosphatase <2.5 times the upper limit of normal unless due to organ involvement.
- Adequate renal function with creatinine levels ≤2 times the upper limit of normal.
- 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.
- 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 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.
- 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
- Subjects have been diagnosed with acute promyelocytic leukemia.
- The subjects are receiving concomitant therapy that includes other chemotherapy that is or may be active against AML, except agents such as hydroxyurea, used to control the WBC count until chemotherapy, up to Day 1 of L-Annamycin administration.
- 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.
- Subjects have central nervous system involvement.
- 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.
- 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.
- Subjects are pregnant, lactating, or not using adequate contraception.
- Subjects have a known allergy to anthracyclines.
- Subjects have ongoing Grade 1 mucositis at the time of entry.
- Subjects are required to use moderate or strong inhibitors and inducers of Cytochrome P450 family of enzymes (CYP) and transporters that cannot be held for 3 days prior to Day 1 and during treatment days.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Day 1 through Day 28
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Day 1 and Day 3
|
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.
|
Between Day 15 and Day 35 (+/- 3 days)
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MB-105
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Leukemia, Myeloid, Acute
-
University of PennsylvaniaActive, not recruitingAcute Myeloid Leukemia, in Relapse | Acute Myeloid Leukemia, Refractory | Acute Myeloid Leukemia, PediatricUnited States
-
Terrence J Bradley, MDImago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New...RecruitingAcute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Acute Myeloid Leukemia, in RelapseUnited States
-
Bhavana BhatnagarCTI BioPharmaCompletedRecurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Therapy-Related Acute Myeloid LeukemiaUnited States
-
Washington University School of MedicineWithdrawnRefractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
-
C. Babis AndreadisGateway for Cancer Research; AVEO Pharmaceuticals, Inc.TerminatedAcute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
-
National Cancer Institute (NCI)RecruitingAcute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingAcute Myeloid Leukemia | Recurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingAcute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Therapy-Related Acute Myeloid LeukemiaUnited States
-
Jacqueline Garcia, MDEli Lilly and CompanyCompletedCombination Merestinib and LY2874455 for Patients With Relapsed or Refractory Acute Myeloid LeukemiaRelapsed Adult Acute Myeloid Leukemia | Refractory Adult Acute Myeloid LeukemiaUnited States
-
University of NebraskaNational Cancer Institute (NCI)Active, not recruitingSecondary Acute Myeloid Leukemia | Therapy-Related Acute Myeloid Leukemia | Adult Acute Myeloid LeukemiaUnited States
Clinical Trials on Liposomal Annamycin
-
Moleculin Biotech, Inc.Active, not recruitingSarcoma,Soft Tissue | Pulmonary MetastasisUnited States
-
Callisto PharmaceuticalsTerminatedAcute Lymphocytic Leukemia | Acute Myelogenous LeukemiaUnited States
-
Maria Sklodowska-Curie National Research Institute...RecruitingSoft Tissue Sarcoma | Pulmonary MetastasisPoland
-
Moleculin Biotech, Inc.CompletedLeukemia, Myeloid, AcuteUnited States
-
NYU Langone HealthNational Cancer Institute (NCI)Completed
-
Callisto PharmaceuticalsUnknownAcute Lymphocytic LeukemiaUnited States
-
Moleculin Biotech, Inc.RecruitingLeukemia, Myeloid, AcuteItaly, Poland
-
National Cancer Institute (NCI)CompletedActinic Keratosis | Squamous Cell Carcinoma of the Skin | Recurrent Skin Cancer | Basal Cell Carcinoma of the SkinUnited States
-
Milton S. Hershey Medical CenterCompleted
-
InnoMedica Schweiz AGActive, not recruitingParkinson DiseaseSwitzerland