Phase 1 Study of LY2523355 in Patients With Acute Leukemia
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Eli Lilly and Company
- Enrollment
- 33
- Locations
- 1
- Primary Endpoint
- Recommended Dose and Schedule for Phase 2 Studies in Acute Leukemia
Study Overview
Brief Summary
This study is a multicenter, nonrandomized, open-label, dose-escalation with intra-patient dose-escalation, Phase 1 study of intravenous LY2523355 to determine the dose of LY2523355 that can be safely administered to participants with acute leukemia. Part A and Part B are dose escalation of two schedules in participants with acute leukemia. Parts A and B will enroll concurrently. Part C is a dose expansion for each schedule in participants with acute myeloblastic leukemia (AML).
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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).
Arms & Interventions
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.
Intervention: LY2523355 (Drug)
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.
Intervention: LY2523355 (Drug)
Outcomes
Primary Outcomes
Recommended Dose and Schedule for Phase 2 Studies in Acute Leukemia
Time Frame: Baseline up to the end of Cycle 2 (Day 42)
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.
Secondary Outcomes
- Number of Participants With Clinically Significant Effects(Baseline up to study completion (up to 213 days))
- Pharmacokinetics, Area Under the Concentration Versus Time Curve (AUC), Single Dose(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)
- Pharmacokinetics, Area Under the Concentration Versus Time (AUC), Multiple Dose(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)
- Response Rates for Chronic Myelogenous Leukemia in Blast Crisis (Complete Hematologic Response, no Evidence of Leukemia, Return to Chronic Phase)(Baseline up to disease progression or discontinuation (up to 213 days))
- Response Rate (Percentage) for Acute Lymphoblastic Leukemia Using The Revised International Working Group Criteria(Baseline up to disease progression or discontinuation (up to 213 days))
- Pharmacokinetics, Maximum Plasma Concentration (Cmax), Single Dose(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)
- Percentage of Participants With a Response for Acute Myelogenous Leukemia Using The Revised International Working Group Criteria(Baseline up to disease progression or discontinuation (up to 213 days))
- Pharmacokinetics, Maximum Plasma Concentration (Cmax), Multiple Dose(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)