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Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Blast Crisis

Acute Disease

Neoplasms by Histologic Type

Hematologic Diseases

Disease Attributes

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Acute Non Lymphoblastic Leukemia

Chronic Myeloid Leukemia

Acute Graft Versus Host Disease

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.

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.

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.

LY2523355

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)

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).

A Study for Patients With Acute Leukemia

Phase 1 Study of LY2523355 in Patients With Acute Leukemia

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Eli Lilly and Company

AEs were listed and the incidence summarized by study part, assigned dose level. For participants that were escalated within their dose group, AEs were counted for both dose levels. Participants who escalated dose are represented in 2 columns.

Dose was 2 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 2, and 3 of every 21-day Cycle.

Cohort 1 LY2523355 2 mg/m^2/Day, Days 1, 2, and 3

Dose was 4 mg/m\^2/day administered by a 1-hour IV infusion on Days 1, 2, and 3 of every 21-day Cycle.

Cohort 1 LY2523355 4 mg/m^2/Day, Days 1, 2, and 3

Dose was 5 mg/m\^2/day administered by a 1-hour IV infusion on Days 1, 2, and 3 of every 21-day Cycle.

Cohort 1 LY2523355 5 mg/m^2/Day, Days 1, 2, and 3

Dose was 6 mg/m\^2/day administered by a 1-hour IV infusion on Days 1, 2, and 3 of every 21-day Cycle.

Cohort 1 LY2523355 6 mg/m^2/Day, Days 1, 2, and 3

Dose was 8 mg/m\^2/day administered by a 1-hour IV infusion on Days 1, 5, and 9 of every 21-day Cycle.

Cohort 2 LY2523355 8 mg/m^2/Day, Days 1, 5, and 9

Dose was 10 mg/m\^2/day administered by a 1-hour IV infusion on Days 1, 5, and 9 of every 21-day Cycle.

Cohort 2 LY2523355 10 mg/m^2/Day, Days 1, 5, and 9

Dose was 12 mg/m\^2/day administered by a 1-hour IV infusion on Days 1, 5, and 9 of every 21-day Cycle.

Cohort 2 LY2523355 12 mg/m^2/Day, Days 1, 5, and 9

Dose was 14 mg/m\^2/day administered by a 1-hour IV infusion on Days 1, 5, and 9 of every 21-day Cycle.

Cohort 2 LY2523355 14 mg/m^2/Day, Days 1, 5, and 9

Cohort 3 LY2523355 5 mg/m^2/Day, Days 1, 2, and 3

Starting dose was 2 milligrams per meter squared per day (mg/m\^2/day) administered by intravenous (IV) infusion over 1 hour on Days 1, 2, and 3 of every 21-day Cycle.

Schedule A LY2523355

Starting dose was 8 mg/m\^2/day administered by IV infusion over 1 hour on Days 1, 5, and 9 of every 21-day Cycle.

Schedule B LY2523355

Starting dose was 5 mg/m\^2/day administered by IV infusion over 1 hour on Days 1, 2, and 3 of every 21-day Cycle.

No participants in Part C escalated from their initial dose.

Schedule C LY2523355

Total

Age, Continuous

Sex: Female, Male

Caucasian

African

Hispanic

Native American

East Asian

West Asian

Race/Ethnicity, Customized

United States

Region of Enrollment

ECOG Status 0

ECOG Status 1

ECOG Status 2

Eastern Cooperative Oncology Group (ECOG) Performance Status classifies patients according to their functional impairment. Scores range from 0 (Fully Active) to 5 (Death) as follows: 0 - Fully Active; 1 - Ambulatory, Restricted Strenuous Activity; 2 - Ambulatory, No Work Activities; 3 - Partially Confined to Bed, Limited Self Care; 4 - Completely Disabled; and 5 - Dead.

Eastern Cooperative Oncology Group (ECOG) Performance Status

Participants who received at least one dose of study medication (LY2523355).

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. The decision was made to close the study because of evident toxicity and lack of efficacy.

Chief Medical Officer

Escalating doses starting at 2 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 2, and 3 of every 21-day Cycle in Part A of the study. Escalating doses starting at 8 mg/m\^2/day administered by a 1-hour IV infusion on Days 1, 5, and 9 of every 21-day Cycle in Part B of the study. Dose of 5 mg/m\^2/day administered by a 1-hour IV infusion on Days 1, 2, and 3 of every 21-day Cycle in Part C of the study.

Recommended Dose and Schedule for Phase 2 Studies in Acute Leukemia

Escalating doses starting at 2 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 2, and 3 of every 21-day Cycle in Part A of the study.

Starting dose was 5 mg/m\^2/day administered by IV infusion over 1 hour on Days 1, 2, and 3 of every 21-day Cycle.

Number of Participants With Clinically Significant Effects

2 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 2, and 3 of every 21-day cycle.

Schedule A 2 mg LY2523355

4 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 2, and 3 of every 21-day cycle.

Schedule A 4 mg LY2524455

Schedule A 5 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 2, and 3 of every 21-day Cycle in Part A and Part C combined.

Schedule A,C 5 mg LY2523355

6 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 2, and 3 of every 21-day cycle.

Schedule A 6 mg LY2523355

8 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 5, and 9 of every 21-day cycle.

Schedule B 8 mg LY2523355

10 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 5, and 9 of every 21-day cycle.

Schedule B 10 mg LY2523355

12 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1,5, and 9 of every 21-day cycle.

Schedule B 12 mg LY2523355

14 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 5, and 9 of every 21-day cycle.

Schedule B 14 mg 2523355

16 mg/m²/day was inadvertently given to a participant.

Schedule B 16 mg LY2523355

Participants who received one dose of LY2523355 on Day 1 of Cycle 1(Schedule A,B,C) with evaluable pharmacokinetic data to enable determination of the LY2523355 plasma Cmax on Day 1. Schedule A,C data was combined for 5 mg, 2 participants received and incorrect dose of 6 mg and 16 mg are included in data.

Pharmacokinetics, Maximum Plasma Concentration (Cmax), Single Dose

2 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 2, and 3 of every 21-day cycle

Schedule A Day 3 2 mg LY2523355

4 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 2, and 3 of every 21-day cycle

Schedule A Day 3 4 mg LY2523355

5 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 2, and 3 of every 21-day cycle.

Schedule A/C Day 3 5 mg LY2523355

Schedule A Day 3 6 mg LY2523355

8 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 5, and 9 of every 21-day cycle

Schedule B Day 9 8 mg LY2523355

10 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 5, and 9 of every 21-day cycle

Schedule B Day 9 10 mg LY2523355

12 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 2, and 3 of every 21-day Cycle in Part A, Part B and Part C.

Schedule B Day 9 12 mg LY2523355

14 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1,5, and 9 of every 21-day cycle

Schedule B Day 9 14 mg LY2523355

Participants who received more than one dose of LY2523355 with evaluable pharmacokinetic data, Schedules A,B,C.

Pharmacokinetics, Maximum Plasma Concentration (Cmax), Multiple Dose

The AUC(0-24)

The AUC(0-inf)

Schedule A Day 1 2 mg LY2523355

Schedule A Day 1 4 mg LY2524455

5 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 2, and 3 of every 21-day Cycle in Part A and Part C combined.

Schedule A,C Day 1 5 mg LY2523355

6 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 2, and 3 of every 21-day cycle

Schedule A Day 1 6 mg LY2523355

Schedule B Day 1 8 mg LY2523355

Schedule B Day 1 10 mg LY2523355

Schedule B Day 1 12 mg LY2523355

Schedule B Day 1 14 mg 2523355

Schedule B Day 1 16 mg LY2523355

Participants who received one dose of LY2523355 on Day 1 of Cycle 1 with evaluable pharmacokinetic data to enable calculation of the LY2523355 AUC on Day 1 of Cycle 1.Schedule A,C data was combined for 5 mg, 2 participants received and incorrect dose of 6 mg and 16 mg are included in data.

Pharmacokinetics, Area Under the Concentration Versus Time Curve (AUC), Single Dose

AUC(0-24)

AUC(0-inf),

Participants who received more than one dose of LY2523355 with evaluable pharmacokinetic data on Cycle 1 Day 3 or Day 9, schedule dependent.

Pharmacokinetics, Area Under the Concentration Versus Time (AUC), Multiple Dose

Starting dose was 2 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 2, and 3 of every 21-day Cycle.

Four of the 10 participants enrolled in Part A escalated from their initial dose after the first cycle (3 participants escalated from 2 to 4 mg/m\^2/day and 1 participant escalated from 5 to 6 mg/m\^2/day).

Schedule A LY2523355 Days 1, 2, and 3

Starting dose was 8 mg/m\^2/day administered by a 1-hour IV infusion on Days 1, 5, and 9 of every 21-day Cycle.

Five of the 15 participants enrolled in Part B escalated from their initial dose after the first cycle (2 participants escalated from 8 to 10 mg/m\^2/day, 1 participant escalated from 8 to 12 mg/m\^2/day, 1 participant escalated from 10 to 12 mg/m\^2/day, and 1 participant escalated from 12 to 14 mg/m\^2/day).

Schedule B LY2523355 Days 1, 5, and 9

Starting dose was 5 mg/m\^2/day administered by a 1-hour IV infusion on Days 1, 5, and 9 of every 21-day Cycle.

No participants in Part C escalated from their initial dose.

Schedule C LY2523355 Days 1, 2, and 3

Participants with acute myelogenous leukemia who received at least one dose of study medication (LY2523355).

Percentage of Participants With a Response for Acute Myelogenous Leukemia Using The Revised International Working Group Criteria

Starting dose was 2 milligrams per meter squared per day (mg/m\^2/day) administered by a 1-hour intravenous (IV) infusion on Days 1, 5, and 9 of every 21-day Cycle.

Four of the 10 participants enrolled in Part A escalated from their initial dose after the first cycle (3 participants escalated from 2 to 4 mg/m\^2/day and 1 participant escalated from 5 to 6 mg/m\^2/day).

Participants with chronic myelogenous leukemia in blast crisis who received at least one dose of study medication (LY2523355).

Response Rates for Chronic Myelogenous Leukemia in Blast Crisis (Complete Hematologic Response, no Evidence of Leukemia, Return to Chronic Phase)

Participants with acute lymphoblastic leukemia who received at least one dose of study medication (LY2523355).

Response Rate (Percentage) for Acute Lymphoblastic Leukemia Using The Revised International Working Group Criteria

Schedule LY2523355 Days 1, 2, and 3

Death of Participants on Study up to the Follow-up Period

Participants received a dose escalation to maximum tolerated dose (MTD) from 2 mg/m²/day to 4,5 and 6 mg/m²/day during a 1 hour (hr) infusion on Days 1,2, 3 (Schedule A) of a 21 day cycle. Participants did not have to escalate doses and participants could join at a higher dose level.

Participants received a dose escalation to maximum tolerated dose (MTD) ranging from 8 mg/m²/day (starting dose) to 10,12 and 14 mg/m²/day during a 1 hour (hr) infusion on Days 1,5, 9 (Schedule B)of a 21 day cycle Participants did not have to escalate doses and participants could join at a higher dose level.

Starting dose was 5 mg/m²/day administered by IV infusion over 1 hour on Days 1, 2, and 3 (Schedule C) of every 21-day Cycle.

Spots Global Cancer Trial Database for A Study for Patients With Acute Leukemia

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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