MLN8237 in Young Patients With Relapsed or Refractory Solid Tumors or Acute Lymphoblastic Leukemia



Status:Archived
Conditions:Cancer, Brain Cancer, Blood Cancer, Leukemia
Therapuetic Areas:Oncology
Healthy:No
Age Range:Any
Updated:7/1/2011
Start Date:September 2008

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A Phase I/II Study of MLN8237, an Oral Selective Small Molecule Inhibitor of Aurora A Kinase, in Children With Relapsed/Refractory Solid Tumors


RATIONALE: MLN8237 may stop the growth of cancer cells by blocking some of the enzymes
needed for cell growth.

PURPOSE: This phase I/II trial is studying the side effects and best dose of MLN8237 and to
see how well it works in treating young patients with relapsed or refractory solid tumors or
acute lymphoblastic leukemia (acute lymphoblastic leukemia closed to accrual as of
02/18/10).


OBJECTIVES:

Primary

- To estimate the maximum tolerated dose and recommended phase II dose of Aurora A kinase
inhibitor MLN8237 administered once daily or twice daily in pediatric patients with
relapsed or refractory solid tumors (except CNS tumors) or acute lymphoblastic leukemia
(ALL). (ALL closed to accrual as of 02/18/10)

- To evaluate the toxicity of this drug in these patients.

- To characterize the pharmacokinetics of this drug in these patients.

Secondary

- To determine the antitumor activity of this drug in these patients. (Phase I)

- To determine the efficacy of this drug, using the once daily dosing schedule, in these
patients. (Phase II)

- To explore the relationship between polymorphic variations in the
UDPglucuronyltransferase gene UGT1A1 and exposure to MLN8237.

- To assess two common polymorphic variants in the Aurora A kinase gene (Phe31Ile and
Val57Ile) thought to potentially influence tumorigenesis.

- To examine the relationship between Aurora A expression status and response to Aurora A
inhibition.

OUTLINE: This is a multicenter phase I, dose escalation followed by a phase II study.
Patients are stratified according to diagnosis (solid tumors vs neuroblastoma vs acute
lymphoblastic leukemia). (Acute lymphoblastic leukemia closed to accrual as of 02/18/10)

Patients receive oral Aurora A kinase inhibitor MLN8237 once or twice daily on days 1-7.
Courses repeat every 21 days for up to 24 months in the absence of disease progression or
unacceptable toxicity.

Whole blood samples are collected from all patients for genotyping for polymorphisms in
UGT1A1 enzymes and polymorphisms in the Aurora A kinase gene. For patients in the phase II
portion of the study, previously preserved tumor tissue blocks and bone marrow or peripheral
blasts are evaluated for Aurora A kinase protein using IHC, mRNA expression, and gene
amplification using FISH or quantitative PCR. Bone marrow is also obtained for FAB
morphology, immunophenotyping, and cytogenetics. Blood samples are also collected
periodically during the first course of therapy for pharmacokinetics studies.


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Ann Arbor, MI 48109Bus: -
Ann Arbor, Michigan 48109
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1802 6th Avenue South
Birmingham, Alabama 35294
(205) 934-4011
UAB Comprehensive Cancer Center One of the nation’s leading cancer research and treatment centers, the...
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300 Longwood Avenue
Boston, Massachusetts 02115
617-355-6000
Children's Hospital - Boston Boston Children's Hospital is a 395-bed comprehensive center for pediatric health...
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450 Brookline Ave
Boston, Massachusetts 2215
(617) 632-3000
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute Founded in 1997, Dana-Farber/Harvard Cancer Center (DF/HCC) was...
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3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
 1-513-636-4200 
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
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Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas From its...
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425 E River Pkwy # 754
Minneapolis, Minnesota 55455
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Masonic Cancer Center at University of Minnesota The Masonic Cancer Center was founded in 1991....
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3181 SW Sam Jackson Park Rd
Portland, Oregon 97239
(503) 494-5058
Knight Cancer Institute at Oregon Health and Science University Cancer takes many forms. Although cancer...
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4800 Sand Point Way Northeast
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Children's Hospital and Regional Medical Center - Seattle Seattle Children
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Brooklyn, New York 11203
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1 Baylor Plaza
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Indianapolis, Indiana 46202
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722 W 168th St
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Columbia Presbyterian Med Ctr On January 1, 1998, The New York Hospital publicly announced its...
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Pittsburgh, Pennsylvania 15213
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660 S Euclid Ave
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Siteman Cancer Center The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University...
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