L-Annamycin for Injection in Combination With Cytarabine Injection as Second Line Therapy for Remission Induction in Adult Subjects With Refractory/Relapsed AML
A Pivotal Phase 2/3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Adaptive Design Study of L Annamycin for Injection in Combination With Cytarabine Injection Versus Placebo in Combination With Cytarabine Injection as Second Line Therapy for Remission Induction in Adult Subjects With Refractory/Relapsed Acute Myeloid Leukemia
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years to 80 Years
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
- Procedures mentioned: Injections, Infusions
Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.
Show the study's own words
- "This pivotal phase 2/3, multi-center, adaptive design study of L-Annamycin for Injection in combination with Cytarabine Injection as second line therapy for remission induction in adult subjects with refractory/relapsed AML is divided into two parts, Part A and Part B."
- "L-Annamycin for Injection will be administered as an intravenous (IV) infusion over 2 hours."
- "The placebo will be administered the same (i.e., IV infusion over 2 hours)."
- "Cytarabine Injection will be administered as an IV infusion over 4 hours."
- "The first day of Cytarabine Injection treatment will start on the first day of L-Annamycin for Injection or placebo treatment (Day 1)."
- "On the days where both Cytarabine Injection and L-Annamycin for Injection or placebo are administered, the Cytarabine Injection infusion will be initiated after the L-Annamycin for Injection or placebo infusion is completed.The recommended time between infusions is 15 minutes (± 5 minutes)."
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests L-Annamycin with cytarabine to help clear signs of acute myeloid leukemia (AML), a blood cancer. It is for adults ages 18 to 80 whose AML did not respond to, or came back after, one prior treatment plan. The study has two parts.
This pivotal phase 2/3, multi-center, adaptive design study of L-Annamycin for Injection in combination with Cytarabine Injection as second line therapy for remission induction in adult subjects with refractory/relapsed AML is divided into two parts, Part A and Part B.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Have AML confirmed by lab tests that meet the study’s standards.
- Have AML that did not respond to, or came back after, only one prior treatment plan.
- Be 18 to 80 years old, able to care for yourself, and expected to live more than six weeks.
- Have no chemotherapy, radiation, or major surgery in the past two weeks, or have recovered from its harmful effects. Some treatments are allowed; infection symptoms must be gone one week before study treatment.
- Have no experimental treatment in the four weeks before study treatment.
- Have liver and kidney test results within the study’s limits.
- Be able to understand and sign the consent form, talk with the study doctor, and follow study rules.
- If able to become pregnant, have a negative blood pregnancy test within 72 hours before treatment. These participants, and men with partners who can become pregnant, must use highly effective birth control and not donate eggs or sperm through six months after the last study dose.
Who can't join
- Have or previously had acute promyelocytic leukemia (APL) or MDS/AML, other blood cancer types; have AML in the brain or spinal cord; or have an FLT3 gene change unless gilteritinib is unavailable in your country.
- Have had radiation to the middle of the chest.
- Have certain heart problems, such as weak pumping, valve disease, abnormal rhythms, heart failure, unstable chest pain, or a heart attack in the past six months; or have severe uncontrolled high blood pressure.
- Have risks for a dangerous heart rhythm, or take medicines that raise this risk, unless the study doctor says the medicine is needed and safe with close checks.
- Have a serious illness, infection, lung disease, or mental health or social issue that could prevent following study rules, or any condition the study doctor considers too risky.
- Have mouth or digestive tract sores now, or have had severe sores from past treatment.
- Have received L-asparaginase, or more than the study’s allowed total dose of anthracyclines, a group of cancer drugs.
- Be pregnant or breastfeeding, or have a known allergy to anthracyclines, cytarabine, ingredients in the study drugs, or contrast dye used for study heart tests.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Inclusion Criteria: 1. Has a pathologically confirmed diagnosis of AML per the 2022 International Consensus Classification (ICC) as adopted in the European LeukemiaNet (ELN) 2022 recommendations for the diagnosis and management of AML. The tests and procedures used to establish the diagnosis of AML should be consistent with the ELN's 2022 recommendations 2. Has refractory/relapsed AML after having received only one prior line of therapy\*. \*A prior line of therapy will be defined as the planned therapy consisting of one or more cycles of episodic treatment or a defined period of continuous treatment. This may consist of single-agent or combination therapy as well as a planned sequence of treatment phases. For example, first-line treatment of AML with induction, consolidation, and alloHSCT is considered one line of therapy. A line of therapy ends when the patient fails to achieve a response within a prespecified period (refractory) or relapses after achieving CR. For the purpose of confirming refractory AML at screening, refractory disease will be defined as CR not being achieved after first line therapy \[i.e., after 1 cycle of intensive therapy or 180 days after commencing less-intensive therapy (shorter durations of less-intensive therapy may be considered for refractory disease on a case by case basis after discussion between the PI and Medical Monitor)\]. 3. Between 18 and 80 years of age (inclusive) at the time of signing the informed consent form (ICF). 4. Has received no chemotherapy, radiation, or major surgery within 2 weeks prior to the first randomized dose of study drug or has recovered from the toxic side effects of that therapy. Hydroxyurea to control white blood cell (WBC) count, supportive measures, and prophylaxes as required under the protocol will be allowed. Treatment of opportunistic or other infections with antibiotics, antifungals, and/or antiviral agents, including therapy for meningeal disease (i.e., intrathecal chemotherapy), per institutional standards of care will be allowed during this period, as long as the symptoms of infection have resolved by 1 week prior to the first dose of randomized study drug. 5. Has received no investigational therapy within 4 weeks prior to the first randomized dose of study drug. 6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at screening. 7. Has a life expectancy of greater than six weeks at screening. 8. Has adequate laboratory results at screening including the following: 1. Total bilirubin ≤2.0 times the upper limit of normal (ULN). For subjects with leukemic involvement or Gilbert Syndrome, total bilirubin must be ≤3.0 ULN. 2. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase \<3.5 times the ULN. For subjects with organ involvement, AST, ALT, and alkaline phosphatase must be ≤4.5 times the ULN. 3. Creatinine clearance ≥60 mL/min (using Cockcroft-Gault equation). 9. Can understand and sign the ICF, can communicate with the PI, and can understand and comply with the requirements of the protocol. 10. For women of childbearing potential (WCBP): Must have a negative serum beta human chorionic gonadotropin (ß-hCG) pregnancy test within 72 hours prior to the first randomized dose of study drug. 11. For WCBP: Must agree to not donate ova and use a highly effective method of birth control from the time of informed consent through 6 months after their last randomized dose of study drug. 12. For males with partners who are WCBP: Must agree to not donate sperm and use a highly effective method of birth control from the time of informed consent through 6 months after their last randomized dose of study drug. Exclusion Criteria: 1. Has prior or current diagnosis of acute promyelocytic leukemia (APL) or myelodysplastic syndrome (MDS)/AML 2. Received prior mediastinal radiotherapy. 3. Has central nervous system involvement. 4. Has impaired cardiac function, including any of the following: 1. Abnormal LVEF at screening \[per American College of Cardiology, normal LVEF is 50 to 70% 2. Valvular heart disease. 3. Severe, uncontrolled hypertension. 4. Uncontrolled cardiac arrhythmias. 5. Recent (≤6 months prior to screening) myocardial infarction. 6. Unstable angina. 7. Symptomatic congestive heart failure. 8. New York Heart Association (NYHA) classification of 3 or 4. 9. QT interval/corrected QT (QTc) interval \>480 msec at screening. 10. History of additional risk factors for torsade des pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome). 11. . Use of concomitant medications with known risk of Torsades de Pointes (TdP) (i.e., drugs that prolong the QT interval and that are clearly associated with a known risk of TdP, even when taken as recommended; refer to Appendix G for examples of such drugs), unless in the clinical judgement of the PI, the medication is imperative and can be used safely with adequate monitoring. 5. Has clinically relevant serious comorbid medical conditions including, but not limited to, active infection, chronic obstructive or chronic restrictive pulmonary disease, history of positive status for human immunodeficiency virus (virus detected in serum) hepatitis B or hepatitis C with current serious symptoms or signs of underlying chronic infection or psychiatric illness/social situations that would limit compliance with study requirements. 6. Has evidence of mucositis/stomatitis at screening or baseline, or has history of severe (≥Grade 3) mucositis/stomatitis from prior therapy. 7. Has any condition that, in the opinion of the PI, places the subject at unacceptable risk if he/she were to participate in the study. 8. Has received prior treatment with L-asparaginase. 9. Pregnant or breastfeeding. 10. Known hypersensitivity to anthracyclines, cytarabine, the excipients of L Annamycin for Injection or Cytarabine Injection, or contrast media that may be used for the protocol-specified GLS assessments. 11. Has received a total cumulative prior anthracycline dose of \> 300 mg/m2 (daunorubicin equivalent dose). 12. Has relapsed or refractory AML with a FLT3 mutation, unless resides in a country where gilteritinib is not available.
Study sites (8)
AL
- University of Alabama Birmingham · Birmingham, AL 35249Rishawn Carriere · Study contact · 205-962-5581 · rcarriere@uabmc.eduManuel Espinoza-Gutarra · Principal investigatorMore trials in Birmingham
FL
- Bioresearch Partners · Miami, FL 33155Jonathan Matias · Study contact · 786-503-4618 · jmatias@bioresearchpartner.comLuis Rangel · Principal investigatorMore trials in Miami
GA
- Augusta University - Georgia Cancer Center · Augusta, GA 30912Megan Johnson · Study contact · 706-721-5095 · mjohnson54@augusta.eduVamsi Kota · Principal investigatorMore trials in Augusta
NE
- University of Nebraska Medical Center · Omaha, NE 68198Amanda Smith · Study contact · 402-596-3223 · amandasmith1@unmc.eduMoataz Ellithi · Principal investigatorMore trials in Omaha
NJ
- Atlantic Health · Morristown, NJ 07960Stephanie Ramirez · Study contact · 973-971-6283 · STEPHANIE.RAMIREZ@ATLANTICHEALTH.ORGMohamad Cherry · Principal investigatorMore trials in Morristown
OH
- University Hospitals Cleveland Medical Center · Cleveland, OH 44106Sarah Gollwitzer · Study contact · 216-286-0112 · Sarah.Gollwitzer@UHhospitals.orgBenjamin Tomlinson, MD · Principal investigatorMore trials in Cleveland
PA
- University of Pennsylvania · Philadelphia, PA 19117Jennifer Fantuzzo · Study contact · 215-275-8300 · jennifer.fantuzzo@pennmedicine.upenn.eduCatherine Lai · Principal investigatorMore trials in Philadelphia
RI
- University of Rhode Island · Providence, RI 02903Sara Jaramillo · Study contact · 401.606.9473 · Sara.Jaramillo@brownhealth.orgJohn Reagan · Principal investigatorMore trials in Providence