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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
33
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.
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.
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.
Indianapolis, Indiana, United States
Recommended Dose and Schedule for Phase 2 Studies in Acute Leukemia
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.
Time frame: Baseline up to the end of Cycle 2 (Day 42)
Number of Participants With Clinically Significant Effects
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.
Time frame: Baseline up to study completion (up to 213 days)
Pharmacokinetics, Maximum Plasma Concentration (Cmax), Single Dose
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.
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
Pharmacokinetics, Maximum Plasma Concentration (Cmax), Multiple Dose
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.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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.
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.
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.
Houston, Texas, United States
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
Pharmacokinetics, Area Under the Concentration Versus Time Curve (AUC), Single Dose
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.
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
Pharmacokinetics, Area Under the Concentration Versus Time (AUC), Multiple Dose
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.
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
Percentage of Participants With a Response for Acute Myelogenous Leukemia Using The Revised International Working Group Criteria
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.
Time frame: Baseline up to disease progression or discontinuation (up to 213 days)
Response Rates for Chronic Myelogenous Leukemia in Blast Crisis (Complete Hematologic Response, no Evidence of Leukemia, Return to Chronic Phase)
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.
Time frame: 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
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.
Time frame: Baseline up to disease progression or discontinuation (up to 213 days)