Safety and Tolerability of AZD1208 and the Pharmacokinetics and Efficacy of AZD1208 in Acute Myelogenous Leukemia (AML) Patients - Full Text View

Purpose

The purpose of this open label study is to evaluate the safety, tolerability, pharmacokinetics, and efficacy of AZD1208 in patients with recurrent or refractory Acute Myelogenous Leukemia (AML). This study will have two parts. In Part A, patients will receive escalating doses to identify the maximum tolerated dose (MTD). In Part B, the efficacy of the maximum tolerated dose will be evaluated in a expanded group of patients.

Condition	Intervention	Phase
Acute Myeloid Leukemia	Drug: AZD1208	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase Ia/Ib, Open-Label, Multicentre, Two-Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of AZD1208 Administered Daily in Adult Patients With Recurrent or Refractory Acute Myelogenous Leukemia (AML)

Resource links provided by NLM:

Genetics Home Reference related topics: familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Acute Myeloid Leukemia Leukemia

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Part A: Number of patients with dose limiting toxicities (DLTs) [Maximum Tolerated Dose (MTD) is defined as the maximum dose level below the dose level at which ≥ 33 % of at least 6 patients of a cohort experience DLTs during cycle 1.] [ Time Frame: 28 days (cycle 1) ] [ Designated as safety issue: Yes ]
Part B: Number of patients with Complete Remission (CR) or CR with incomplete blood count recovery (CRi) [ Time Frame: From baseline until disease progression or discontinuation from study (expected duration of treatment: approximately 3 months) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Part A and B: Number of patients with adverse events and serious adverse events [ Time Frame: From cycle 1 day 1 until treatment discontinuation (expected duration of treatment: approximately 3 months) ] [ Designated as safety issue: Yes ]
Part A and B: Description of the pharmacokinetics (PK) of AZD1208 in terms of area under plasma concentration-time curve(AUC), maximum plasma concentration (Cmax), and time to maximum plasma concentration (Tmax) [ Time Frame: Cycle 1Day 1- pre-dose through 24 hours post dose and Cycle 1 Day 14 - pre-dose through 24 hours post-dose. Interval timepoints : predose, 30 mins, 1 hour(hr), 1.5hr, 2hr , 3hr, 6hr , 8hr, 24 hours and at same timepoints at Cycle 1 Day 14. ] [ Designated as safety issue: No ]
Part A and B: Description of urine pharmacokinetics (PK) of AZD1208 in terms of the cumulative amount of drug excreted unchanged into urine from zero to time and renal clearance [ Time Frame: Cycle 1Day 1- pre-dose through 24 hours post dose and Cycle 1 Day 14 - pre-dose through 24 hours post-dose.during 0 - 24 hours after dosing. ] [ Designated as safety issue: No ]
Part A and B: Number of patients with response of Complete Remission(CR), CR with incomplete blood count recovery, Partial Remission, or Morphologic Leukemia-Free [ Time Frame: From baseline until disease progression or discontinuation from study (expected duration of treatment: approximately 3 months) ] [ Designated as safety issue: No ]
Part B: Duration of CR or CRi based on time from first documentation of CR to relapse [ Time Frame: From baseline until disease progression or discontinuation from study (expected duration of treatment: approximately 3 months) ] [ Designated as safety issue: No ]

Estimated Enrollment:	74
Study Start Date:	February 2012
Estimated Study Completion Date:	January 2015
Estimated Primary Completion Date:	October 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: AZD1208 Single ascending dose escalation of 3 - 6 patient cohorts until maximum tolerated dose (MTD) is established. Up to 12 patients may be included at any dose not determined to be intolerable. Safety expansion using MTD in up to 44 Acute myelogenous leukemia (AML) patients.	Drug: AZD1208 Daily oral doses of AZD1208 for 28 day cycles until progression or unacceptable toxicity develops. Starting dose will be 120 mg and will be escalated in successive cohorts until an MTD is established.

Detailed Description:

A Phase Ia/Ib, Open-Label, Multicentre, Two-Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of AZD1208 Administered Daily in Adult Patients with Recurrent or Refractory Acute Myelogenous Leukemia (AML).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Males or females at least 18 years of age
Patients with relapsed or refractory Acute myelogenous leukemia (AML) or AML secondary to myelodysplastic syndromes, myeloproliferative neoplasm, or chronic myelogenous leukemia
Eastern Oncology Cooperative Group (ECOG) performance status 0-2 and considered likely to complete at least 4 weeks of therapy

Exclusion Criteria:

With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment.
As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and HIV.
Active heart disease including myocardial infarction within the last 3 months, symptomatic coronary artery disease, clinically significant arrhythmias not controlled by medication or uncontrolled congestive heart failure
Prior allogeneic transplant requiring immunosuppressive therapy (Patients with prior allogeneic transplants who remain clinically stable for ≥ 2 weeks or more off immunosuppressive therapy, are eligible) • White blood cell count ≥ 100,000/mm3 (100x10*9/L)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01489722

Contacts

Contact: AstraZeneca Clinical Study Information

800-236-9933

information.center@astrazeneca.com

Locations

United States, Massachusetts
Research Site	Recruiting
Boston, Massachusetts, United States
United States, Texas
Research Site	Recruiting
Houston, Texas, United States
Canada
Research Site	Recruiting
Toronto, Canada

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director:

Becker Hewes, MD

Sponsor GmbH

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01489722 History of Changes
Other Study ID Numbers:	D4510C00001
Study First Received:	November 22, 2011
Last Updated:	March 20, 2013
Health Authority:	Canada: Canadian Institutes of Health Research Canada: Ethics Review Committee Canada: Health Canada United States: Federal Government United States: Food and Drug Administration

Keywords provided by AstraZeneca:

Leukemia
AML
AZD1208

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on May 23, 2013