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Study Summary
No. 2009-0172:.......Leukemia......Hagop Kantarjian......Leukemia
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Study Summary Title
Study Summary
Number:
2009-0172
Study Title:A Phase I, open-label, multi-centre, multiple ascending dose study to assess
the safety and tolerability of AZD1152 in combination with low dose
cytosine arabinoside (LDAC) in patients with acute myeloid leukaemia
(AML)
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Physician New Patient Referral
Name:Hagop KantarjianPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:LeukemiaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-7026
Contact us about clinical trials
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General Information
Disease Group:LeukemiaSupported By:AstraZeneca
Phase of Study:Phase IReturn
Visit:
Days 1-10, 15, and 22 of each cycle; Day 28 of the last cycle if 3 cycles or
less, or Day 1 of cycle 4; 28 days after the last dose of study medication.
Treatment
Agents:
AZD1152
Cytarabine
Home Care:N/A
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this clinical research study is to find the highest tolerable dose
of AZD1152 that can be given in combination with low dose cytosine arabinoside
(LDAC) to patients with AML. The safety of this drug combination will also be
studied.
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Study Objectives / Outcomes
Primary Objectives
To evaluate the safety and tolerability, and determine a recommended Phase II dose of AZD1152 in combination with LDAC.

Secondary Objectives
To determine the pharmacokinetics of AZD1152, AZD1152 hQPA and LDAC when AZD1152 is given in combination with LDAC, and to compare to their pharmacokinetics when given alone.

Exploratory Objectives
  • To make a preliminary assessment of the efficacy of AZD1152 combined with LDAC, as evaluated by the Investigator.
  • To collect and store DNA, derived from a saliva sample, for potential exploratory research into genes that may influence the response to AZD1152 (and agents used in combination or as comparators) and/or development of AML. Genes that may be analysed include, but are not limited to, MDR1, MRP1, Flt3, p53, p51 and aurora kinase B.
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Study Status Information
Study Activation / Registration Date:06/05/2009
IRB Review and Approval Date:05/01/2009
Study Type:Phase I
Recruitment Status:Open
Projected Accrual:18
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Provision of written informed consent prior to any study specific procedures

2) Newly diagnosed male or female patients aged >/= 60 years

3) De Novo (primary) or Secondary AML

4) Not eligible for intensive induction chemotherapy because of medical, social or psychological reasons

5) World Health Organisation (WHO) performance status 0-3 (WHO performance status 3 is only acceptable if solely attributed to the underlying leukaemia)

6) Serum bilirubin </= 1.5 x Upper Limit of Normal (ULN) unless considered due to leukaemic organ involvement (Gilbert's or related syndrome allowed)

7) Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) </= 2.5 x ULN, unless considered due to leukaemic organ involvement

8) Serum creatinine < 1.5 x ULN or 24-hour creatinine clearance > 50 mL/min (measured or calculated by Cockcroft-Gault)

9) Likely ability to complete 3 cycles (12 weeks) of treatment

10) Evidence of post-menopausal status*, or negative urinary or serum pregnancy test for female pre-menopausal patients.

11) * Post menopausal females are defined as follows: natural menopause with menses > 1 year ago; or radiation-induced oophorectomy with last menses > 1 year ago; or chemotherapy induced menopause with 1 year interval since last menses; or serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and plasma oestradiol levels in the postmenopausal range for the institution; or bilateral oopherectomy or hysterectomy.

12) For inclusion in this genetic research, patients must fulfil all of the inclusion criteria described in the main body of the study protocol and: • Provide informed consent for the genetic sampling and analyses

Exclusion Criteria:1) Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site and/or agents for AstraZeneca)

2) Previous administration of treatment in the present study

3) Participation in another clinical study in which an investigational product was received within 14 days before the first dose in this study, or at any time if the patient has not recovered from side-effects associated with that investigational product (to CTCAE Grade 1 or baseline, except alopecia)

4) Administration of LDAC is clinically contraindicated

5) Patients with AML of French-American-British (FAB) M3 classification Acute Promyelocytic Leukaemia (APL)

6) Patients with blast crisis of chronic myeloid leukaemia

7) QTc interval >/= 470 ms, from a single ECG reading or a mean of three ECG readings, using Fridericia's or Bazzett's correction

8) Any chemotherapy e.g. for prior MDS, or radiotherapy, within 14 days prior to starting the study (not including palliative radiotherapy at local sites)

9) Persistent, chronic, clinically significant toxicities, from any prior anti-cancer therapy greater than CTCAE Grade 1 (except alopecia)

10) Patients with symptomatic clinically defined central nervous system (CNS) disease (asymptomatic patients are eligible if symptom free for > 10 days)

11) Uncontrolled intercurrent illness including, but not limited to, uncontrolled active infection, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations which would limit compliance with protocol requirements

12) Major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that involved general anaesthesia or respiratory assistance

13) Patients with documented cases of human immunodeficiency virus (HIV) or hepatitis B or C

14) Female patients who are breast feeding, or patients of reproductive potential not employing an effective method of birth control

15) History of hypersensitivity to active or inactive excipients of any study medication (AZD1152 or LDAC)

16) Exclusion from this genetic research may be for any of the exclusion criteria specified in the main study or any of the following: Previous allogenic bone marrow transplant; Blood transfusion in the last 120 days of genetic sample collection which was not leukocyte depleted

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Links
Registration Number: NCT00926731
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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