- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01214655
A Study for Patients With Acute Leukemia
Phase 1 Study of LY2523355 in Patients With Acute Leukemia
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Illinois
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Chicago, Illinois, United States
- 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.
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Indiana
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Indianapolis, Indiana, United States
- 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.
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Massachusetts
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Boston, Massachusetts, United States
- 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.
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Tennessee
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Nashville, Tennessee, United States
- 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.
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Texas
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Houston, Texas, United States
- 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.
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Dose escalation period for both schedules:
- Participants must have a confirmed diagnosis of acute leukemia regardless of sub-type and for whom experimental Phase 1 therapy is appropriate.
- Are greater than or equal to 18 years of age.
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
- Females with childbearing potential must have had a negative urine or serum pregnancy test less than or equal to 7 days prior to the first dose of study drug.
Dose confirmation period for both schedules:
- Participant must have a confirmed diagnosis of untreated acute myeloblastic leukemia (AML), should not be a candidate for standard therapy, and a clinical trial is a preferred treatment option or have acute AML that is relapsed or refractory to no more than 2 prior induction regimens. Hydroxyurea to control prior blast counts is not considered a prior regimen.
- Are greater than or equal to 60 years of age.
- Have a performance status of 0 or 1 on the ECOG scale.
- Females with childbearing potential must have had a negative urine or serum pregnancy test less than or equal to 7 days prior to the first dose of study drug.
Exclusion Criteria:
- Have received treatment within 28 days of the initial dose of study drug with a drug that has not received regulatory approval for any indication.
- Participants with known central nervous system (CNS) leukemia by spinal fluid cytology or imaging. A lumbar puncture is not required unless CNS involvement is clinically suspected. Participants with signs or symptoms of leukemic meningitis or a history of leukemic meningitis must have a negative lumbar puncture within 2 weeks of study enrollment.
- Have other active malignancy (with the exception of basal and squamous cell skin cancer) at time of study entry.
- Have had an autologous or allogenic bone marrow transplant within 3 months. All organ toxicity must be resolved.
- Have evidence of graft-versus-host disease due to an allogenic bone marrow transplant.
- Have uncontrolled systemic infection.
- Females who are pregnant or lactating.
- Have known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb) (screening not required).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: LY2523355 on Days 1, 2, and 3
Starting dose was 2 milligrams per meter squared (mg/m^2) administered by a 1-hour intravenous (IV) infusion on Days 1, 2, and 3 of every 21-day Cycle.
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Administered as a 1-hour IV infusion for at least 2 cycles.
Cycle length is 21 days.
Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
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EXPERIMENTAL: LY2523355 on Days 1, 5, and 9
Starting dose was 8 milligrams per meter squared (mg/m^2) administered by a 1-hour IV infusion over 1 hour on Days 1, 5, and 9 of every 21-day Cycle.
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Administered as a 1-hour IV infusion for at least 2 cycles.
Cycle length is 21 days.
Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Recommended Dose and Schedule for Phase 2 Studies in Acute Leukemia
Time Frame: Baseline up to the end of Cycle 2 (Day 42)
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The recommended dose and schedule for Phase 2 studies of LY2523355 with acute leukemia was determined by a modification of the continual reassessment method.
The sample size to adequately determine the maximum tolerated dose (MTD) for both schedules in this study was a function of a priori estimates for the dose-toxicity relationship as well as the initial dose in each schedule, the rate of dose escalation, and the observed dose-toxicity relationship.
Before MTD could be determined for Part B (Days 1, 5, and 9 of a 21-day cycle), this study was paused for futility analysis.
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Baseline up to the end of Cycle 2 (Day 42)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With Clinically Significant Effects
Time Frame: Baseline up to study completion (up to 213 days)
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Clinically significant effects were defined as serious and other non-serious adverse events (AEs). A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
Baseline up to study completion (up to 213 days)
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Pharmacokinetics, Maximum Plasma Concentration (Cmax), Single Dose
Time Frame: Cycle 1(Day 1),: Predose, 1 hour (hr), 2 hr, 3 hr, 4 hr, 6 hr, 8, hr, 12 hr, 24 hr, 48 hr, 72 hr postdose
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The maximum plasma concentration (Cmax) was the maximum plasma concentration obtained from the plasma concentration versus time curves of LY2523355 were calculated to assess intra and intercycle variability, depending on dosage cycle.
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Cycle 1(Day 1),: Predose, 1 hour (hr), 2 hr, 3 hr, 4 hr, 6 hr, 8, hr, 12 hr, 24 hr, 48 hr, 72 hr postdose
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Pharmacokinetics, Maximum Plasma Concentration (Cmax), Multiple Dose
Time Frame: Days 3 (Parts A or C) or 9 (Part B), Cycle 1: Predose, 1 hour (hr), 2 hr, 3 hr, 4 hr, 6 hr, 8, hr, 12 hr, 24 hr, 48 hr, 72 hr postdose
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The maximum plasma concentration (Cmax) was the maximum plasma concentration obtained from the plasma concentration versus time curves of LY2523355.
Multiple dose LY2523355 plasma Cmax values are shown at each dose level for both schedules of administration (Day 3 of Cycle 1 for the Day 1, 2, and 3 schedule of administration and Day 9 of Cycle 1 for the Days 1, 5, and 9 schedule of administration).
The maximum plasma concentration (Cmax) was the maximum plasma concentration obtained from the plasma concentration versus time curves of LY2523355 were calculated to assess intra and intercycle variability, depending on dosage cycle.
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Days 3 (Parts A or C) or 9 (Part B), Cycle 1: Predose, 1 hour (hr), 2 hr, 3 hr, 4 hr, 6 hr, 8, hr, 12 hr, 24 hr, 48 hr, 72 hr postdose
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Pharmacokinetics, Area Under the Concentration Versus Time Curve (AUC), Single Dose
Time Frame: Day 1, Cycle 1: Predose, 1 hour (hr), 2 hr, 3 hr, 4 hr, 6 hr, 8, hr, 12 hr, 24 hr, 48 hr, 72 hr postdose
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The AUC(0-24) was calculated from area under the plasma concentration versus time curves of LY2523355 from time zero to 24 hours. The AUC(0-inf) was calculated from area under the plasma concentration versus time curves of LY2523355 from time zero to infinity. Single dose LY2523355 AUC values are shown for each dose level for Day 1 of Cycle 1 for both schedules of administration. When only individual participant parameters are available or N=2, for a given dose, the AUC CV is not calculated for that dose group and is not presented (4 milligrams per meter squared per day [mg/m^2/day], 14 mg/m^2/day, 12 mg/m^2/day and 16 mg/m^2/day). Individual data will be presented. |
Day 1, Cycle 1: Predose, 1 hour (hr), 2 hr, 3 hr, 4 hr, 6 hr, 8, hr, 12 hr, 24 hr, 48 hr, 72 hr postdose
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Pharmacokinetics, Area Under the Concentration Versus Time (AUC), Multiple Dose
Time Frame: Days 3 (Parts A or C) or 9 (Part B):Predose, 1 hour (hr), 2 hr, 3 hr, 4 hr, 6 hr, 8, hr, 12 hr, 24 hr 48 hr, 72 hr postdose
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The AUC(0-24) was calculated from area under the plasma concentration versus time curves of LY2523355 from time zero to 24 hours. The AUC(0-inf) was calculated from area under the plasma concentration versus time curves of LY2523355 from time zero to infinity.. Multiple dose LY2523355 AUC values are shown at each dose level for both schedules of administration (Day 3 of Cycle 1 for the Day 1, 2, and 3 schedule of administration and Day 9 of Cycle 1 for the Days 1, 5, and 9 schedule of administration). When only individual participant parameters are available or N=2, for a given dose, the AUC CV is not calculated for that dose group and is not presented (4 milligrams per meter squared per day [mg/m^2/day], 12 mg/m^2/day, and 14 mg/m^2/day). Individual data will be presented. |
Days 3 (Parts A or C) or 9 (Part B):Predose, 1 hour (hr), 2 hr, 3 hr, 4 hr, 6 hr, 8, hr, 12 hr, 24 hr 48 hr, 72 hr postdose
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Percentage of Participants With a Response for Acute Myelogenous Leukemia Using The Revised International Working Group Criteria
Time Frame: Baseline up to disease progression or discontinuation (up to 213 days)
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Response rate for participants with acute myelogenous leukemia include the proportion of participants who achieved a morphologic complete remission, morphologic complete remission with incomplete blood count recovery, cytogenetic complete remission, molecular complete remission, or partial remission.
The Revised International Working Group Criteria was used to determine response rate for participants with acute myelogenous leukemia.
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Baseline up to disease progression or discontinuation (up to 213 days)
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Response Rates for Chronic Myelogenous Leukemia in Blast Crisis (Complete Hematologic Response, no Evidence of Leukemia, Return to Chronic Phase)
Time Frame: Baseline up to disease progression or discontinuation (up to 213 days)
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Response rate for participants with chronic myelogenous leukemia in blast crisis include the proportion of participants who achieved a complete hematologic response, had no evidence of leukemia, or had returned to chronic phase.
The criteria outlined in Cohen 2005 (Cohen MH, Johnson JR, Pazdur R. 2005.
U.S. Food and Drug Administration Drug Approval Summary: conversion of imatinib mesylate (STI571; Gleevec) tablets from accelerated approval to full approval.
Clin Cancer Res.
11(1):12-19.)
was used to determine response rate for participants with chronic myelogenous leukemia in blast crisis.
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Baseline up to disease progression or discontinuation (up to 213 days)
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Response Rate (Percentage) for Acute Lymphoblastic Leukemia Using The Revised International Working Group Criteria
Time Frame: Baseline up to disease progression or discontinuation (up to 213 days)
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Response rate for participants with acute lymphoblastic leukemia include the proportion of participants who achieved a morphologic complete remission, morphologic complete remission with incomplete blood count recovery, cytogenetic complete remission, molecular complete remission, or partial remission.
The Revised International Working Group Criteria was used to determine response rate for participants with acute lymphoblastic leukemia by early treatment assessment, morphologic leukemia-free state (less than 5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells) and morphologic complete remission (and have an absolute neutrophil count of more than 1000 per microliter and platelets of 100,000 per microliter.
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Baseline up to disease progression or discontinuation (up to 213 days)
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Death of Participants on Study up to the Follow-up Period
Time Frame: Baseline up to end of treatment follow-up (up to 213 days)
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The number of participants who died through the follow-up period of the study. This does not include the outcomes for the two participants who died while on treatment through Cycle 2 as captured in the Participant Flow Table. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
Baseline up to end of treatment follow-up (up to 213 days)
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 12119
- I1Y-MC-JFBC (OTHER: Eli Lilly and Company)
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.
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