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A Study for Patients With Acute Leukemia

Primary Purpose

Acute Leukemia

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
LY2523355
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Leukemia focused on measuring Acute Myelogenous Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia,Blast Crisis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

LY2523355 on Days 1, 2, and 3

LY2523355 on Days 1, 5, and 9

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
October 1, 2010
Last Updated
May 10, 2019
Sponsor
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT01214655
Brief Title
A Study for Patients With Acute Leukemia
Official Title
Phase 1 Study of LY2523355 in Patients With Acute Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Terminated
Why Stopped
Primary objective has been met in the absence of clinically meaningful remissions
Study Start Date
June 2008 (undefined)
Primary Completion Date
February 2011 (Actual)
Study Completion Date
February 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company

4. Oversight

Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Leukemia
Keywords
Acute Myelogenous Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia,Blast Crisis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LY2523355 on Days 1, 2, and 3
Arm Type
Experimental
Arm Description
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.
Arm Title
LY2523355 on Days 1, 5, and 9
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
LY2523355
Intervention Description
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.
Primary Outcome Measure Information:
Title
Recommended Dose and Schedule for Phase 2 Studies in Acute Leukemia
Description
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)
Secondary Outcome Measure Information:
Title
Number of Participants With Clinically Significant Effects
Description
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)
Title
Pharmacokinetics, Maximum Plasma Concentration (Cmax), Single Dose
Description
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
Title
Pharmacokinetics, Maximum Plasma Concentration (Cmax), Multiple Dose
Description
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.
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
Title
Pharmacokinetics, Area Under the Concentration Versus Time Curve (AUC), Single Dose
Description
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
Title
Pharmacokinetics, Area Under the Concentration Versus Time (AUC), Multiple Dose
Description
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
Title
Percentage of Participants With a Response for Acute Myelogenous Leukemia Using The Revised International Working Group Criteria
Description
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)
Title
Response Rates for Chronic Myelogenous Leukemia in Blast Crisis (Complete Hematologic Response, no Evidence of Leukemia, Return to Chronic Phase)
Description
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)
Title
Response Rate (Percentage) for Acute Lymphoblastic Leukemia Using The Revised International Working Group Criteria
Description
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)
Other Pre-specified Outcome Measures:
Title
Death of Participants on Study up to the Follow-up Period
Description
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.
Time Frame
Baseline up to end of treatment follow-up (up to 213 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
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.
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
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.
City
Indianapolis
State/Province
Indiana
Country
United States
Facility Name
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.
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
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.
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
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.
City
Houston
State/Province
Texas
Country
United States

12. IPD Sharing Statement

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A Study for Patients With Acute Leukemia

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