A Phase 2 Trial of MLN8237 in Adult Patients With Acute Myelogenous Leukemia and High-Grade Myelodysplastic Syndrome - Full Text View

Purpose

This is an open-label, multicenter, phase 2 study of MLN8237 in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

Condition	Intervention	Phase
Acute Myelogenous Leukemia High-Grade Myelodysplastic Syndrome	Drug: MLN8237	Phase 2

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 2 Trial of MLN8237, an Oral Aurora A Kinase Inhibitor, in Adult Patients With Acute Myelogenous Leukemia and High-Grade Myelodysplastic Syndrome

Resource links provided by NLM:

Genetics Home Reference related topics: familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Acute Myeloid Leukemia Leukemia Myelodysplastic Syndromes

U.S. FDA Resources

Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:

Response rate: partial remission plus complete remission (PR + CR) [ Time Frame: Extent of disease measured by CBC with differential prior to every cycle, and bone marrow aspiration and biopsy at baseline, then bone marrow aspirate at end of Cycles 1 and 2, and then every other cycle (end of Cycles 4, 6, etc.). ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression free survival (PFS) and duration of response (DOR) [ Time Frame: CBC prior to every cycle, bone marrow at baseline, end Cycles 1, 2, every other cycle. ] [ Designated as safety issue: No ]
Safety and tolerability of MLN8237 treatment based on vital signs, physical examination, laboratory tests, and adverse events [ Time Frame: Duration of therapy through 30 days after the last dose. ] [ Designated as safety issue: Yes ]

Enrollment:	57
Study Start Date:	February 2009
Study Completion Date:	September 2011
Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 MLN8237	Drug: MLN8237 MLN8237 will be administered orally (PO) at a dose of 50 mg twice daily (BID) for seven consecutive days followed by a 14-day rest period, in 21-day cycles. Dose reductions will be implemented in the setting of drug-related toxicities. The first dose of MLN8237 on Cycle 1, Day 1 will be administered in the study clinic. Patients will continue to receive repeated cycles of MLN8237 treatment for up to 12 months, or until there is evidence of disease progression or unacceptable treatment-related toxicity. Treatment with MLN8237 may be continued beyond 12 months if it is determined that a patient would clearly derive benefit from continued therapy.

Arms

Assigned Interventions

Experimental: 1

MLN8237

Drug: MLN8237

MLN8237 will be administered orally (PO) at a dose of 50 mg twice daily (BID) for seven consecutive days followed by a 14-day rest period, in 21-day cycles. Dose reductions will be implemented in the setting of drug-related toxicities.

The first dose of MLN8237 on Cycle 1, Day 1 will be administered in the study clinic. Patients will continue to receive repeated cycles of MLN8237 treatment for up to 12 months, or until there is evidence of disease progression or unacceptable treatment-related toxicity. Treatment with MLN8237 may be continued beyond 12 months if it is determined that a patient would clearly derive benefit from continued therapy.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Each patient must meet all of the following inclusion criteria:

Male or female patients 18 years or older
Eligible diagnoses:
- Acute myelogenous leukemia (except APL) with > 10% bone marrow or peripheral blood blasts; failed to achieve CR or relapse after prior therapy, not candidates for potentially curative treatment. Untreated patients > 60 are eligible if not candidates for standard induction.
- High-grade MDS, defined by all the following features: IPSS Intermediate-2 or High Risk; > 10% blasts on bone marrow examination; treatment failure from, or not candidates for, standard therapies including demethylating agents, eg azacytidine or decitabine.
Eastern Cooperative Oncology Group perf. status 0-2
Female patients:
- Postmenopausal for at least one year
- Surgically sterile, or
- If childbearing potential, agree to practice two effective methods of contraception or abstain from heterosexual intercourse.
Male patients:
- Practice effective barrier contraception to one month after the last dose of study drug, or
- Abstain from heterosexual intercourse.
Voluntary written consent
Patients on hydroxyurea may be included

Exclusion Criteria:

Pregnant or lactating females
Known human immunodeficiency virus (HIV) positive or AIDS-related illness
Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the protocol completion
Total bilirubin > 1.5 × the upper limit of normal (ULN)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 × the ULN. AST, ALT may be elevated to 5 x the ULN if reasonably ascribed to underlying hematological disorder.
Calculated creatinine clearance < 30 mL/minute
Antineoplastic or radiotherapy within 14 days preceding the first dose
Myocardial infarction within 6 months of enrollment or current history of New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
Major surgery 14 days prior to the first dose
Clinically uncontrolled central nervous system (CNS) involvement.
Inability to swallow capsules
History of uncontrolled sleep apnea or conditions that result in excessive daytime sleepiness, such as chronic lung disease

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00830518

Locations

United States, New Jersey
Hematology and Oncology Associates of Northern New Jersey
Morristown, New Jersey, United States, 07962

Sponsors and Collaborators

Millennium Pharmaceuticals, Inc.

Investigators

Study Director:

Medical Monitor

Millennium Pharmaceuticals, Inc.

More Information

No publications provided

Responsible Party:	Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00830518 History of Changes
Other Study ID Numbers:	C14005
Study First Received:	January 27, 2009
Last Updated:	January 26, 2012
Health Authority:	United States: Food and Drug Administration Canada: Health Canada France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia

Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions

ClinicalTrials.gov processed this record on May 19, 2013