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

Primary Purpose

Acute Myeloid Leukemia

Status

Terminated

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

AZD1208

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Leukemia, AML, AZD1208

Eligibility Criteria

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

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)

Sites / Locations

Research Site
Research Site
Research Site
Research Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AZD1208

Arm Description

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.

Outcomes

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.]

Part B: Number of patients with Complete Remission (CR) or CR with incomplete blood count recovery (CRi)

Secondary Outcome Measures

Part A and B: Number of patients with adverse events and serious adverse events

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)

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

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

Part B: Duration of CR or CRi based on time from first documentation of CR to relapse

Full Information

NCT ID

NCT01489722

First Posted

November 22, 2011

Last Updated

August 10, 2015

Sponsor

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT01489722

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

August 2015

Overall Recruitment Status

Terminated

Study Start Date

February 2012 (undefined)

Primary Completion Date

May 2014 (Actual)

Study Completion Date

May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia

Keywords

Leukemia, AML, AZD1208

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

55 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AZD1208

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

AZD1208

Intervention Description

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.

Primary Outcome Measure Information:

Title

Time Frame

28 days (cycle 1)

Title

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)

Secondary Outcome Measure Information:

Title

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)

Title

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.

Title

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.

Title

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)

Title

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)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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) 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Frank Neumann, MD

Organizational Affiliation

Sponsor GmbH

Official's Role

Study Director

Facility Information:

Facility Name

Research Site

City

Boston

State/Province

Massachusetts

Country

United States

Facility Name

Research Site

City

St. Louis

State/Province

Missouri

Country

United States

Facility Name

Research Site

City

Houston

State/Province

Texas

Country

United States

Facility Name

Research Site

City

Toronto

State/Province

Ontario

Country

Canada

12. IPD Sharing Statement

Links:

URL

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=1500&filename=D4510C00001_CSR_Synopsis.pdf

Description

D4510C00001_CSR_Synopsis.pdf

Learn more about this trial

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

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