Safety, Tolerability, Pharmacokinetics and Efficacy of AZD1208 in Acute Myelogenous Leukemia (AML) Patients

Acute Myeloid Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01489722
• Other study ID #: D4510C00001
• Status: Terminated
• Phase: Phase 1
• First received: November 22, 2011
• Last updated: August 10, 2015
• Start date: February 2012
• Est. completion date: May 2014

Study information

• Verified date: August 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Canadian Institutes of Health ResearchCanada: Ethics Review CommitteeCanada: Health CanadaUnited States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 55
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

• Type 1 Diabetes or uncontrolled Type II Diabetes

• HbA1C =8% or fasting blood glucose >160 mg/Dl (>8.9 mmol/L)

• Baseline fasting total cholesterol >300 mg/dL (>7.75 mmol/L)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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.

Locations

Country	Name	City	State
Canada	Research Site	Toronto	Ontario
United States	Research Site	Boston	Massachusetts
United States	Research Site	Houston	Texas
United States	Research Site	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.]		28 days (cycle 1)	Yes
Primary	Part B: Number of patients with Complete Remission (CR) or CR with incomplete blood count recovery (CRi)		From baseline until disease progression or discontinuation from study (expected duration of treatment: approximately 3 months)	No
Secondary	Part A and B: Number of patients with adverse events and serious adverse events		From cycle 1 day 1 until treatment discontinuation (expected duration of treatment: approximately 3 months)	Yes
Secondary	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)		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.	No
Secondary	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		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.	No
Secondary	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		From baseline until disease progression or discontinuation from study (expected duration of treatment: approximately 3 months)	No
Secondary	Part B: Duration of CR or CRi based on time from first documentation of CR to relapse		From baseline until disease progression or discontinuation from study (expected duration of treatment: approximately 3 months)	No

External Links

•   D4510C00001_CSR_Synopsis.pdf