Clinical trial NCT00486265: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acute Myelogenous Leukemia
Keywords: Phase I
Phase II
acute myelogenous leukemia
AML
cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2007-06-14
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: To Identify a Maximum Tolerated Dose (MTD) of AZD4877 by Assessment of the Incidence of Dose-limiting Toxicities (DLTs)
timeFrame: Dose-limiting toxicities (DLTs) are evaluated during the first induction treatment course administered during the initial 15-day treatment period.
measure: To Assess the Effect of AZD4877 on the Rate of Complete Remission (CR)
timeFrame: Response is evaluated after a maximum of 2 courses of induction therapy.
measure: To Determine the PK Profile of AZD4877 [ Time Frame: Daily x 3 Schedule ]
timeFrame: 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 outcomes:
measure: To Assess the Effect of AZD4877 on Rate and Duration of CR, CRi, PR and Overall Response (CR,CRi, or PR)
timeFrame: Response is evaluated after a maximum of 2 courses of induction therapy.
measure: 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
timeFrame: 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.
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Houston
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Toronto
country: Canada
facility: Research Site
state: Ontario
Study officials:
affiliation: AstraZeneca
name: Gregory A Curt, MD
role: STUDY_DIRECTOR
References:
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.