A Phase 2 Trial of MLN8237 in Adult Participants With Acute Myelogenous Leukemia and High-Grade Myelodysplastic Syndrome

NCT00830518 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: C140052008-006977-34U1111-1187-6569
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Acute Myelogenous Leukemia; High-Grade Myelodysplastic Syndrome

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate (ORR) Based on Investigator's Assessment

  Best ORR is defined as the number of participants with complete remission(CR) or partial remission(PR) assessed by the Investigator using modified AML/MDS International Working Group(IWG) Criteria. AML:CR=neutrophils \>1x10\^9/L, platelets \>100x10\^9/L, bone marrow blasts(BMB) \<5%, transfusion independent, no extramedullary disease(EMD); CRi=BMB \<5%, transfusion independent, no EMD; PR=neutrophils \>1x10\^9/L, platelets \>100x10\^9/L, BMB \>50% decrease and 5% to 25%, blasts \<5% with Auer rods; PRi=BMB \>50% decrease and 5% to 25%. MDS:CR=bone marrow: ≤5% myeloblasts with normal maturation, peripheral blood: hemoglobin ≥11 g/dL, platelets ≥100x10\^9/L, neutrophils ≥1.0x10\^9/L, blasts 0%; PR=all CR criteria if abnormal before treatment except: BMB decreased by ≥50% over pretreatment but still \>5%; PRi=BMB decreased by ≥50% over pretreatment but still \>5%; Marrow CR=bone marrow: ≤5% myeloblasts and decrease by ≥50% over pretreatment, peripheral blood hematologic improvement responses noted.

  Baseline and every 2 cycles up to Cycle 16 (up to Month 12), from Cycle 17 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Approximately 2.4 years)

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  Baseline and every 2 cycles up to Cycle 16 (up to Month 12), from Cycle 17 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Approximately 2.4 years)

• Duration of Response (DOR)

  Baseline and every 2 cycles up to Cycle 16 (up to Month 12), from Cycle 17 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Approximately 2.4 years)

• Best Overall Hematologic Improvement (HI) Response for Myelodysplastic Syndrome Based on Investigator Assessment

  Baseline and every 2 cycles up to Cycle 16 (up to Month 12), from Cycle 17 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Approximately 2.4 years)

• Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths

  First dose of study drug to 30 days after last dose (Up to 18.9 months)

• Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events

  First dose of study drug to 30 days after last dose (Up to 18.9 months)

Study Arms (1)

Alisertib

EXPERIMENTAL

Alisertib 50 mg, capsules, orally, twice daily for 7 days, followed by 14-day washout period, in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 26 Cycles).

Drug: Alisertib

Interventions

Alisertib DRUG

Alisertib capsules

Also known as: MLN8237

Alisertib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants 18 years or older
• Eligible diagnoses:
• Acute myelogenous leukemia (except acute promyelocytic leukemia \[APL\]) with \> 10% bone marrow or peripheral blood blasts; failed to achieve complete response (CR) or relapse after prior therapy, not candidates for potentially curative treatment. Untreated participants \> 60 are eligible if not candidates for standard induction.
• High-grade myelodysplastic syndrome (MDS), defined by all the following features: International Prognostic Scoring System (IPSS) Intermediate-2 or High Risk; \> 10% blasts on bone marrow examination; treatment failure from, or not candidates for, standard therapies including demethylating agents, e.g. azacytidine or decitabine.
• Eastern Cooperative Oncology Group performance status 0-2
• Female participants:
• 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 participants:
• Practice effective barrier contraception to one month after the last dose of study drug, or
• Abstain from heterosexual intercourse.
• Voluntary written consent
• Participants on hydroxyurea may be included

You may not qualify if:

• Pregnant or lactating females
• Known human immunodeficiency virus (HIV) positive or acquired immune deficiency syndrome (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

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (1)

Hematology and Oncology Associates of Northern New Jersey

Morristown, New Jersey, 07962, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

MLN 8237

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2009
• First Posted: January 28, 2009
• Study Start: February 10, 2009
• Primary Completion: February 2, 2010
• Study Completion: July 4, 2011
• Last Updated: May 11, 2018
• Results First Posted: May 11, 2018

Record last verified: 2018-04

Locations

US (1)