MDACC Study Summary 2006-0177

Study Summary
No. 2006-0177:.......Leukemia......Hagop Kantarjian......Leukemia

Study Summary Title



Study Summary Number:	2006-0177

Study Title:	A Phase I/IIa Open-label Study to Assess the Safety, Tolerability and Preliminary Efficacy of AT9283, a Small Molecule Inhibitor of Aurora Kinases, in Patients with Acute Leukemias, Chronic Myeloid Leukemia, High-Risk Myelodysplastic Syndromes or Myelofibrosis

Physician

New Patient Referral



Name:	Hagop Kantarjian	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Leukemia	Referring 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

General Information



Disease Group:	Leukemia	Supported By:	N/A

Phase of Study:	Phase I/Phase II	Return Visit:	Two additional visits following the treatment period (on Days 5 and 8) every 3 weeks A treatment withdrawal visit will be required when treatment is stopped, within 30 days of last dose of study medicine.

Treatment Agents:	AT9283	Home Care:	NA

Treatment Loc:	Independent Multicenter Arrangements

Estimated Length of Stay in Houston:	In-patient stay on each of 4 days for treatment cycle 1 and then as in or out-patient visits, depending on which is best


Description/ Intervention:	The goal of this research study is to investigate the safety and effectiveness of the study drug AT9283 when given as an intravenous infusion for 4 days. Researchers want to perform testing on your blood to find out how your body handles and processes the study drug.

Study Objectives / Outcomes

Primary objectives

To evaluate the safety and tolerability of AT9283 in patients with acute leukemias, CML, high-risk myelodysplastic syndromes or myelofibrosis with myeloid metaplasia (MMM) for whom standard therapeutic options have failed or who are unsuitable for or refuse standard therapies.

To assess the safety, tolerability and preliminary efficacy of the maximum tolerated dose (MTD) in patients likely to derive clinical benefit.

Secondary objectives

To establish appropriate dose(s) and optimal duration of infusion for AT9283 for use in future studies of patients with acute leukemias, CML, MDS or MMM.

To determine the pharmacokinetics (PK) of AT9283 when administered intravenously to patients with acute leukemias, CML, MDS or MMM.

To demonstrate the pharmacodynamic activity of AT9283 in patients with acute leukemias, CML, MDS or MMM by establishing its effects on relevant biological endpoints.

Exploratory objectives

To perform future genetic analyses of leukemic or myelodysplastic cells as indicated by emerging data.

To obtain buccal smears and peripheral blood samples for DNA extraction for future pharmacogenetic analysis and other potential correlative markers of AT9283 activity.

To explore the preliminary efficacy of MTD₁₄₄

Study Status Information



Study Activation / Registration Date:	07/27/2006

IRB Review and Approval Date:	05/17/2006

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Open

Projected Accrual:	85

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 signed written informed consent

2) Histological or cytological confirmation of one of the following: a) relapsed or refractory AML or ALL; acute leukaemia in patients who are unsuitable for or refuse standard therapy, b) CML in chronic phase, accelerated phase or blast crisis that is resistant or refractory to standard therapy, c) High-risk MDS, defined as the presence of: i) Refractory anemia with excess blasts (RAEB, 5-19% bone marrow blasts), or ii) RAEB in transformation to AML (RAEBT with 20-30% bone marrow blasts),

3) Continued from #2: d) Advanced MMM defined by the presence of one or more of the following features i) Hemoglobin < 10 gm/dL (100 g/L), ii) Platelet count < 100 x 10^9/L (100,000/muL), iii) White blood cell count < 4 x 10^9/L (4,000/muL) iv) symptomatic splenomegaly or other disease-related symptoms inadequately controlled by conventional therapies

4) ECOG performance status 0, 1 or 2

5) Male or female, age 18 years or older

6) Negative pregnancy test or history of surgical sterility or evidence of post-menopausal status (post-menopausal status is defined as any of the following: natural menopause with menses >1 year ago; radiation induced oophorectomy with last menses >1 year ago; chemotherapy induced menopause with 1 year interval since last menses).

Exclusion Criteria:

1) Inadequate liver function as demonstrated by serum bilirubin >/=1.5 times the upper limits of reference range (ULRR) or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or alkaline phosphatase (ALP) >/=2.5 times the ULRR (or >/=5 times the ULRR in the presence of liver metastases)

2) Impaired renal function as demonstrated either by an isolated creatinine value of >/=1.5 times the ULRR OR creatinine clearance < 50 mL/min determined by Cockcroft-Gault formula. Note there is no requirement to determine a formal creatinine clearance if the patient's serum creatinine value is >/=1.5 times the ULRR.

3) Radiotherapy or chemotherapy within the 14 days prior to the first dose of AT9283 being administered (Day 1, dose level 1). Planned use of hydroxyurea other than as is permitted.

4) Receiving an investigational anti-cancer treatment concurrently or within 14 days prior to the start of AT9283 infusion (Day 1)

5) Unresolved CTCAE grade 2 or greater toxicity (other than stable toxicity) from previous anti-cancer therapy excluding alopecia

6) Any evidence of severe or uncontrolled systemic conditions (e.g., severe hepatic impairment) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol

7) Active, uncontrolled central nervous system disease

8) Left ventricular ejection fraction (LVEF) < 50% measured by either echocardiogram or multiple uptake gated acquisition scanning (MUGA)

9) Ischemic heart disease or myocardial infarction or unstable cardiac disease within 3 months of study entry

10) Prior infection with human immunodeficiency virus (HIV), hepatitis B or C viruses – screening for viral infections is not required for entry to this study

11) Major surgery within 28 days prior to the start of AT9283 infusion (Day 1) – excluding skin biopsies and procedures for insertion of central venous access devices

Links

Registration Number: NCT00522990
Study Information on Clinical Trials Registry (clinicaltrials.gov)