Back to resultsPhase I/II, Open-label, Multi-center, Two Part Dose-escalation, Safety, Pharmacokinetics (PK) and Efficacy Study of AZD4877 in Patients With Acute Myelogenous Leukemia (AML)
Primary Purpose
Acute Myelogenous Leukemia
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AZD4877
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myelogenous Leukemia focused on measuring Phase I, Phase II, acute myelogenous leukemia, AML, cancer
Eligibility Criteria
Inclusion Criteria:
- Part A: Relapsed or refractory leukemia for which no standard therapies are anticipated to result in a durable remission
- Part B: AML who have had no more than two prior relapses or failed to achieve remission after at least one induction treatment.
- Patients with prior allogeneic transplants who remain clinically stable for ≥2 weeks or more off immunosuppressive therapy
Exclusion Criteria:
- Promyelocytic acute myelogenous leukemia
- Prior allogeneic transplant requiring immunosuppressive therapy or treating physician does not consider patient to be a candidate for allogeneic transplantation.
- Liver injury
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
Outcomes
Primary Outcome Measures
To Identify a Maximum Tolerated Dose (MTD) of AZD4877 by Assessment of the Incidence of Dose-limiting Toxicities (DLTs)
To identify a maximum tolerated dose (MTD) of AZD4877 by assessment of the incidence of dose-limiting toxicities (DLTs)
To Assess the Effect of AZD4877 on the Rate of Complete Remission (CR)
Marrow response is assessed by modified Cheson criteria for Acute Myelogenous Leukemia (AML). Possible outcomes for marrow response are CR (Complete Remission), CRi (Complete Remission with incomplete blood count recovery), PR (Partial Remission), and treatment failure.
To Determine the PK Profile of AZD4877 [ Time Frame: Daily x 3 Schedule ]
Maximum plasma concentration, Cmax
Secondary Outcome Measures
To Assess the Effect of AZD4877 on Rate and Duration of CR, CRi, PR and Overall Response (CR,CRi, or PR)
Marrow response is assessed by modified Cheson criteria for Acute Myelogenous Leukemia (AML). Possible outcomes for marrow response are CR (Complete Remission), CRi (Complete Remission with incomplete blood count recovery), PR (Partial Remission), and treatment failure.
To Evaluate the Safety and Tolerability of AZD4877 on a Daily x 3 Schedule by Assessment of Adverse Events, Non-hematologic Labs and Vital Signs
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00486265
Brief Title
Phase I/II, Open-label, Multi-center, Two Part Dose-escalation, Safety, Pharmacokinetics (PK) and Efficacy Study of AZD4877 in Patients With Acute Myelogenous Leukemia (AML)
Official Title
A Phase I/II, Open-Label, Multi-Center, Two-Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of AZD4877 Administered on Days 1, 2 and 3 in Adult Patients With Recurrent or Refractory Acute Myelogenous Leukemia (AML) Excluding Promyelocytic Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
July 2010
Overall Recruitment Status
Terminated
Why Stopped
AML assess. of response in Part B patients find treatment failure in all 8 evaluable for marrow response following a maximum of 2 induction courses of therapy
Study Start Date
July 2007 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
July 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
AstraZeneca
4. Oversight
5. Study Description
Brief Summary
The primary purpose of this study is to find out what the maximum tolerated dose is for an experimental drug called AZD4877 based on the side effects experienced by patients that receive AZD4877 on a daily times 3 schedule in acute myelogenous leukemia (AML).
For enrollment information see the Central Contact information below
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myelogenous Leukemia
Keywords
Phase I, Phase II, acute myelogenous leukemia, AML, cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
AZD4877
Intervention Description
intravenous infusion administered on days 1, 2 and 3
Primary Outcome Measure Information:
Title
To Identify a Maximum Tolerated Dose (MTD) of AZD4877 by Assessment of the Incidence of Dose-limiting Toxicities (DLTs)
Description
To identify a maximum tolerated dose (MTD) of AZD4877 by assessment of the incidence of dose-limiting toxicities (DLTs)
Time Frame
Dose-limiting toxicities (DLTs) are evaluated during the first induction treatment course administered during the initial 15-day treatment period.
Title
To Assess the Effect of AZD4877 on the Rate of Complete Remission (CR)
Description
Marrow response is assessed by modified Cheson criteria for Acute Myelogenous Leukemia (AML). Possible outcomes for marrow response are CR (Complete Remission), CRi (Complete Remission with incomplete blood count recovery), PR (Partial Remission), and treatment failure.
Time Frame
Response is evaluated after a maximum of 2 courses of induction therapy.
Title
To Determine the PK Profile of AZD4877 [ Time Frame: Daily x 3 Schedule ]
Description
Maximum plasma concentration, Cmax
Time Frame
PK samples are collected on Days 1, 2, 3, 24 and 48 hours following the end of Day 3 AZD4877 infusion and Day 8.
Secondary Outcome Measure Information:
Title
To Assess the Effect of AZD4877 on Rate and Duration of CR, CRi, PR and Overall Response (CR,CRi, or PR)
Description
Marrow response is assessed by modified Cheson criteria for Acute Myelogenous Leukemia (AML). Possible outcomes for marrow response are CR (Complete Remission), CRi (Complete Remission with incomplete blood count recovery), PR (Partial Remission), and treatment failure.
Time Frame
Response is evaluated after a maximum of 2 courses of induction therapy.
Title
To Evaluate the Safety and Tolerability of AZD4877 on a Daily x 3 Schedule by Assessment of Adverse Events, Non-hematologic Labs and Vital Signs
Time Frame
Patients were followed for safety from the date of first dose of AZD4877 up to 30-days after the last administration of AZD4877, where possible.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Part A: Relapsed or refractory leukemia for which no standard therapies are anticipated to result in a durable remission
Part B: AML who have had no more than two prior relapses or failed to achieve remission after at least one induction treatment.
Patients with prior allogeneic transplants who remain clinically stable for ≥2 weeks or more off immunosuppressive therapy
Exclusion Criteria:
Promyelocytic acute myelogenous leukemia
Prior allogeneic transplant requiring immunosuppressive therapy or treating physician does not consider patient to be a candidate for allogeneic transplantation.
Liver injury
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gregory A Curt, MD
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
Country
United States
Facility Name
Research Site
City
San Antonio
State/Province
Texas
Country
United States
Facility Name
Research Site
City
Toronto
State/Province
Ontario
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
21494838
Citation
Kantarjian HM, Padmanabhan S, Stock W, Tallman MS, Curt GA, Li J, Osmukhina A, Wu K, Huszar D, Borthukar G, Faderl S, Garcia-Manero G, Kadia T, Sankhala K, Odenike O, Altman JK, Minden M. Phase I/II multicenter study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD4877 in patients with refractory acute myeloid leukemia. Invest New Drugs. 2012 Jun;30(3):1107-15. doi: 10.1007/s10637-011-9660-2. Epub 2011 Apr 15.
Results Reference
derived
Learn more about this trial
Phase I/II, Open-label, Multi-center, Two Part Dose-escalation, Safety, Pharmacokinetics (PK) and Efficacy Study of AZD4877 in Patients With Acute Myelogenous Leukemia (AML)
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