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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
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Description
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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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: AZD1208 Phase 1

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).
Study Design
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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

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Arms and Interventions
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Arm Intervention/treatment
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.


Outcome Measures
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Primary Outcome Measures :
  1. 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) ]
  2. 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 Measures :
  1. 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) ]
  2. 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. ]
  3. 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. ]
  4. 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) ]
  5. 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) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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)
  • 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)
Contacts and Locations
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Information from the National Library of Medicine

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


Locations
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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
Sponsors and Collaborators
AstraZeneca
Investigators
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Study Director: Frank Neumann, MD Sponsor GmbH
More Information
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Additional Information:

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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
Keywords provided by AstraZeneca:
Leukemia
AML
AZD1208
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms