Safety, Tolerability, Pharmacokinetics and Efficacy of AZD1208 in Acute Myelogenous Leukemia (AML) Patients
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ClinicalTrials.gov Identifier: NCT01489722 |
Recruitment Status :
Terminated
First Posted : December 12, 2011
Last Update Posted : August 11, 2015
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Condition or disease | Intervention/treatment | Phase |
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Acute Myeloid Leukemia | Drug: AZD1208 | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 55 participants |
Allocation: | Non-Randomized |
Intervention Model: | Single Group Assignment |
Masking: | None (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) |
Study Start Date : | February 2012 |
Actual Primary Completion Date : | May 2014 |
Actual Study Completion Date : | May 2014 |

Arm | Intervention/treatment |
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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.
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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. |
- 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) ]
- 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) ]
- 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) ]
- 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. ]
- 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. ]
- 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) ]
- 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) ]

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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)

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01489722
United States, Massachusetts | |
Research Site | |
Boston, Massachusetts, United States | |
United States, Missouri | |
Research Site | |
St. Louis, Missouri, United States | |
United States, Texas | |
Research Site | |
Houston, Texas, United States | |
Canada, Ontario | |
Research Site | |
Toronto, Ontario, Canada |
Study Director: | Frank Neumann, MD | Sponsor GmbH |
Responsible Party: | AstraZeneca |
ClinicalTrials.gov Identifier: | NCT01489722 |
Other Study ID Numbers: |
D4510C00001 |
First Posted: | December 12, 2011 Key Record Dates |
Last Update Posted: | August 11, 2015 |
Last Verified: | August 2015 |
Leukemia AML AZD1208 |
Leukemia Leukemia, Myeloid, Acute Leukemia, Myeloid Neoplasms by Histologic Type Neoplasms |