- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00620321
A Study of LY2181308 Sodium in Patients With Relapsed or Refractory Acute Myeloid Leukemia
August 26, 2019 updated by: Eli Lilly and Company
An Open-Label Phase 2 Trial of LY2181308 Sodium Administered in Combination With Idarubicin and Cytarabine to Patients With Refractory or Relapsed Acute Myeloid Leukemia
The purpose of this study is to understand the safety profile of LY2181308 sodium administered in combination with idarubicin and cytarabine to patients with relapsed or refractory acute myeloid leukemia (AML).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
24
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Michigan
-
Ann Arbor, Michigan, United States, 48105
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
-
-
Texas
-
Houston, Texas, United States, 77030
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patients who have a diagnosis of acute myeloid leukemia that is relapsed or refractory to at least 1 prior treatment for leukemia, or patients with chronic myeloid leukemia (CML) who are in myeloid blast crisis which have failed at least 1 previous tyrosine kinase inhibitor (TK1). A baseline bone marrow assessment is required less than or equal to 96 hours prior to the first dose of study drug.
- Must have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, immunotherapy, cancer related hormone therapy, or other investigational therapy for at least 21 days for myelosuppressive agents (such as cytarabine, daunorubicin, and gemtuzumab ozogamicin) or 14 days for non-myelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (such as neurotoxicity, diarrhea, and mucositis) except for residual myelosuppression and alopecia. Hydroxyurea is permitted to control the peripheral blast cell count, but must be stopped at least 24 hours before study drug administration.
- Must have adequate organ function.
- Females must have a negative pregnancy test. Male and female patients must agree to use a reliable method of birth control during and for 6 months following the last dose of study drug.
- Patients must be at least 18 years old.
Exclusion Criteria:
- Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a non-myelosuppressive or myelosuppressive agent, respectively.
- Patients with acute promyelocytic leukemia (APML).
- Major surgery within 4 weeks of study enrollment.
- Patients with serious pre-existing medical conditions (at the discretion of the investigator). Because of the known cardiac toxicity of anthracyclines, patients with pre-existing ejection fraction (EF) less than or equal to 45% should not participate in this study. No patient should exceed the maximum exposure of anthracycline doses (for example, idarubicin greater than 120 mg/m²).
- Patients with a second malignancy that could affect the interpretation of the results.
- Patients with leukemic involvement of the central nervous system (CNS) by spinal fluid cytology or imaging.
- Patients with known coagulopathy or bleeding disorder, other than leukemia related thrombocytopenia. Patients with severe of life threatening bleeding refractory to platelet transfusions are also excluded.
- Concomitant anticoagulant therapy (with the exception of heparinized saline to maintain the patency of central venous catheters).
- Women who are pregnant or breast feeding.
- Patients with a known hypersensitivity to oligonucleotides, idarubicin, and/or cytarabine.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: LY2181308 sodium, idarubicin, cytarabine
|
750 milligrams (mg) is administered as a 3-hour intravenous infusion on Days 1, 2, 3, 8, 15, 22 of Cycle 1 (28 days) and Days 1, 8, 15, 22 of Cycle 2 (28 days) until disease progression or unacceptable toxicity develops.
1.5 grams per square meter (g/m²) will be administered as a 4-hour intravenous infusion on Days 3, 4, 5 of Cycle 1 (28 days) and Days 1, 2, 3 of Cycle 2 (28 days) until disease progression or unacceptable toxicity develops.
12 milligrams per square meter (mg/m²) will be administered as a 30-minute intravenous infusion on Days 3, 4, 5 of Cycle 1 (28 days) and on Days 1, 2, 3 of Cycle 2 (28 days) until disease progression or unacceptable toxicity develops.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Adverse Events (Safety Profile)
Time Frame: Start of treatment to study completion up to 6.7 months
|
Data are presented as number of participants who experienced serious adverse events (SAE) and possibly drug-related treatment-emergent adverse events (TEAE) during the study including the 21-day follow-up period.
A summary of serious adverse events and other nonserious adverse events regardless of causality is located in the Reported Adverse Events section.
|
Start of treatment to study completion up to 6.7 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Response to LY2181308 Sodium in Combination With Idarubicin and Cytarabine (Remission Rates)
Time Frame: Baseline to progression of disease or death up to 6 months
|
Response is complete remission (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) + cytoreduction.
CR: fewer than 5% blasts based on a cell count of at least 200 cells from a bone marrow aspirate containing bone marrow spicules, in the setting of peripheral blood recovery to: platelets ≥100x10⁹/liter (L), neutrophils ≥10⁹/L.
PR: defined as a decrease of at least 50% in blast count on the bone marrow aspirate; or cytoreduction (defined as a decrease in blast count not meeting the criteria for a PR or CR).
Response rate is calculated as a total number of participants with CR or CRi or PR or cytoreduction divided by the total number of participants treated multiplied by 100.
|
Baseline to progression of disease or death up to 6 months
|
Relapse-Free Survival
Time Frame: Baseline to progression of disease or death up to 6 months
|
Relapse-Free Survival was defined as the time from first objective status assessment of complete remission (CR) or CR with incomplete blood count recovery (CRi) or partial remission (PR) or cytoreduction to the first time of disease progression or death as a result of any cause.
CR: fewer than 5% blasts based on a cell count of at least 200 cells from a bone marrow aspirate containing bone marrow spicules, in the setting of peripheral blood recovery to: platelets ≥100x10⁹/liter (L), neutrophils ≥10⁹/L.
PR: defined as a decrease of at least 50% in blast count on the bone marrow aspirate; or cytoreduction (defined as a decrease in blast count not meeting the criteria for a PR or CR).
There were too few participants who had a documented progression of disease or death event amongst the participants with a response of CR, CRi, PR or cytoreduction to conduct the time-to-event analysis, thus the relapse-free survival was not analyzed.
|
Baseline to progression of disease or death up to 6 months
|
Area Under the Curve of LY2181308 Over the Dosing Interval
Time Frame: Day 3: 0,12,24,36,48,60,72,84,96,108,120,132 hours
|
Area under the curve of LY2181308 over the dosing interval
|
Day 3: 0,12,24,36,48,60,72,84,96,108,120,132 hours
|
Pharmacodynamics: Number of Participants With Survivin Protein Expression
Time Frame: 6 Months
|
Pharmacodynamics: Number of participants with Survivin Protein Expression.
|
6 Months
|
Change From Baseline in Survivin Index at Day 2
Time Frame: Baseline, Day 2
|
Data presented are the ratio of Day 2 survivin index to the baseline survivin index.
Survivin is a protein expressed in tumor cells, including acute myeloid leukemia (AML), which regulates mitosis and prevents tumor cell death.
Survivin index was calculated as ([blast survivin mean equivalent fluorochrome (MEFL) - blast isotypic control MEFL]/blast isotypic control MEFL).
|
Baseline, Day 2
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Who Died Due to Progressive Disease or Unknown Cause During the 21 Days Post Study Treatment Follow-Up
Time Frame: Study treatment discontinuation up to 21 days post study treatment discontinuation
|
Deaths due to progressive disease (PD) and unknown cause are not considered adverse events.
Deaths due to PD and unknown cause occurring during the 21-day follow-up period after treatment discontinuation are reported here and for those occurring while participants were on treatment are reported in the Participant Flow.
Deaths due to serious adverse events occurred during the study including the 21-day follow-up period are reported in the Reported Adverse Events section.
|
Study treatment discontinuation up to 21 days post study treatment discontinuation
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT-5 hours, EST), Eli Lilly and Company
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2008
Primary Completion (Actual)
January 1, 2010
Study Completion (Actual)
January 1, 2010
Study Registration Dates
First Submitted
February 4, 2008
First Submitted That Met QC Criteria
February 11, 2008
First Posted (Estimate)
February 21, 2008
Study Record Updates
Last Update Posted (Actual)
September 9, 2019
Last Update Submitted That Met QC Criteria
August 26, 2019
Last Verified
August 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antibiotics, Antineoplastic
- Cytarabine
- Idarubicin
Other Study ID Numbers
- 11631
- H8Z-MC-JACU (Other Identifier: Eli Lilly and Company)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
IPD Sharing Time Frame
Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later.
Data will be indefinitely available for requesting.
IPD Sharing Access Criteria
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- CSR
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 Acute Myeloid Leukemia
-
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
-
Kronos BioActive, not recruitingAcute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States, Spain
-
Massachusetts General HospitalExelixisCompletedRefractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
Clinical Trials on LY2181308 sodium
-
Eli Lilly and CompanyWithdrawnHepatocellular CarcinomaGermany, Spain, France, United States
-
Eli Lilly and CompanyCompletedNon-small Cell Lung CancerItaly, United States, Germany, Poland, Belgium, United Kingdom
-
Eli Lilly and CompanyCompletedProstate CancerSpain, Poland, Germany, United States
-
Institut d'Anesthesiologie des Alpes MaritimesUniversité de Nice Sophia Antipolis; Medical University of GrenobleCompleted
-
University of DelawareCompletedBlood Pressure | Cerebrovascular ReactivityUnited States
-
Radboud University Medical CenterUnknownType1diabetes | Hypoglycemia UnawarenessNetherlands
-
Austin HealthCompletedSystemic Inflammatory Response Syndrome | Renal Impairment | OliguriaAustralia
-
Medical University of GrazCompleted
-
Brigham and Women's HospitalCompleted