Alisertib (MLN8237) or Investigator's Choice in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma
A Phase 3, Randomized, Two-Arm, Open-Label, Multicenter, International Trial of Alisertib (MLN8237) or Investigator's Choice (Selected Single Agent) in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma
5 other identifiers
interventional
271
29 countries
145
Brief Summary
This is a phase 3, randomized, 2-arm, open-label, international trial evaluating alisertib compared with single-agent treatment, as selected by the investigator from the offered options of pralatrexate or gemcitabine or romidepsin, in participants with relapsed or refractory peripheral T-cell lymphoma (PTCL). Note: romidepsin was not used as a single-agent comparator outside the United States of America (USA) as supply was not available.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jun 2012
Longer than P75 for phase_3
145 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 28, 2011
CompletedFirst Posted
Study publicly available on registry
December 1, 2011
CompletedStudy Start
First participant enrolled
June 11, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
December 18, 2017
CompletedResults Posted
Study results publicly available
July 31, 2018
CompletedJuly 31, 2018
July 1, 2018
3.1 years
November 28, 2011
May 9, 2018
July 6, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Overall Response Rate (ORR) Based on Independent Review Committee (IRC) Assessment
ORR was defined as the percentage of participants who achieve Complete Response (CR) or Partial Response (PR) as assessed by the IRC using International Working Group (IWG) criteria. CR=Disappearance of all evidence of disease and PR=Regression of measurable disease and no new sites.
Every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years
Progression-Free Survival (PFS) Based on IRC Assessment
PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death due to any cause, whichever occurred first.
Every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years
Secondary Outcomes (11)
Overall Survival (OS)
Participants were followed for survival for 2 years from date of last participant off study treatment, or death, whichever occurs first. Contacts were every 4 months (Median follow-up 519 days in the alisertib arm and 586 days in the comparative arm)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
First dose to 30 days after last dose of study drug or comparator (Up to 152 Weeks)
Number of Participants With Clinically Important Abnormal Laboratory Values Reported as AEs
First dose to 30 days after last dose of study drug or comparator (Up to 152 Weeks)
Number of Participants With Clinically Important Vital Sign Measurements Reported as AEs
First dose to 30 days after last dose of study drug or comparator (Up to 152 Weeks)
Complete Response (CR) Rate
At the end of every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until PD (approximately 3 years)
- +6 more secondary outcomes
Study Arms (2)
Alisertib
EXPERIMENTALAlisertib 50 mg, enteric-coated tablet formulation, orally, twice daily for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle (Up to 148 Weeks).
Pralatrexate, or Romidepsin, or Gemcitabine
ACTIVE COMPARATORPralatrexate 30 mg/m\^2, intravenous (IV) push over 3 to 5 minutes, once weekly, for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles were repeated every 7-weeks provided the participant continued to benefit from and tolerate the therapy (Up to 115 Weeks), or Gemcitabine 1,000 mg/m\^2 over 30 minutes, intravenously, on Days 1, 8, and 15 of a 28-day cycle until the absence of disease progression or unacceptable toxicity (Up to 32 Weeks), or Romidepsin 14 mg/m\^2, intravenously over a 4-hour period, on Days 1, 8, and 15 of a 28-cycle. Cycles were repeated every 28 days provided the patient continued to benefit from and tolerate the therapy (Up to 30 Weeks).
Interventions
Eligibility Criteria
You may qualify if:
- Male or female participants age 18 or older
- Participants with Peripheral T cell lymphoma (PTCL) (selected subtypes) according to World Health Organization (WHO) criteria and have relapsed or are refractory to at least 1 prior systemic, cytotoxic therapy for PTCL. Participants must have received conventional therapy as a prior therapy. Cutaneous-only disease is not permitted. Participants must have documented evidence of progressive and measurable disease.
- Tumor biopsy available for central hematopathologic review
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Female participants who are post menopausal for at least 1 year, surgically sterile, or agree to practice 2 effective methods of contraception through 30 days after the last dose of study drug or agree to abstain from heterosexual intercourse.
- Male participants who agree to practice effective barrier contraception through 6 months after the last dose of alisertib or agree to abstain from heterosexual intercourse
- Suitable venous access
- Voluntary written consent
You may not qualify if:
- Known central nervous system lymphoma
- Systemic antineoplastic therapy, immunotherapy, investigational agent or radiation therapy within 4 weeks of first dose of study treatment or concomitant use during study
- Prior administration of an Aurora A kinase-targeted agent, including alisertib; or all of the 3 comparator drugs (pralatrexate, or romidepsin or gemcitabine; or known hypersensitivity)
- History of uncontrolled sleep apnea syndrome or other conditions that could result in excessive daytime sleepiness
- Cardiac condition as specified in study protocol, including left ventricular ejection fraction (LVEF) \<40%
- Concomitant use of other medicines as specified in study protocol
- Participants with abnormal gastric or bowel function who require continuous treatment with H2-receptor antagonists or proton pump inhibitors
- Known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C
- Autologous stem cell transplant less than 3 months prior to enrollment
- Participants who have undergone allogeneic stem cell or organ transplantation any time
- Inadequate blood levels, bone marrow or other organ function as specified in study protocol
- The participant must have recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade ≤ 1 toxicity, to participant's baseline status (except alopecia), or deemed irreversible from the effects of prior cancer therapy
- Major surgery, serious infection, or infection requiring systemic antibiotic therapy within 14 days prior to the first dose of study treatment
- Female participants who are breastfeeding or pregnant
- Coexistent second malignancy or history of prior solid organ malignancy within previous 3 years
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (151)
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Birmingham, Alabama, United States
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La Jolla, California, United States
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Orlando, Florida, United States
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Tampa, Florida, United States
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Indianapolis, Indiana, United States
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Iowa City, Iowa, United States
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Boston, Massachusetts, United States
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Detroit, Michigan, United States
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Rochester, Minnesota, United States
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Jefferson City, Missouri, United States
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St Louis, Missouri, United States
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Lebanon, New Hampshire, United States
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Hackensack, New Jersey, United States
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Buffalo, New York, United States
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New York, New York, United States
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Syracuse, New York, United States
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Durham, North Carolina, United States
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Columbus, Ohio, United States
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Toledo, Ohio, United States
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Charleston, South Carolina, United States
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Houston, Texas, United States
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Burlington, Vermont, United States
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Seattle, Washington, United States
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Morgantown, West Virginia, United States
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Adelaide, Australia
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Concord, Australia
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Gosford, Australia
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Hobart, Australia
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St Leonards, Australia
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Graz, Austria
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Innsbruck, Austria
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Salzburg, Austria
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Vienna, Austria
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Minsk Didtrict, Belarus
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Vitebsk, Belarus
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Bruges, Belgium
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Brussels, Belgium
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Ghent, Belgium
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Kortrijk, Belgium
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Turnhout, Belgium
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Yvoir, Belgium
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Belo Horizonte, Brazil
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Campianas, Brazil
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Caxias do Sul, Brazil
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Curitiba, Brazil
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Goiânia, Brazil
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Porto Alegre, Brazil
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Porto Alegre/rs, Brazil
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Rio de Janeiro, Brazil
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Salvador, Brazil
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SAO Paulo - SP, Brazil
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São Paulo, Brazil
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Pleven, Bulgaria
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Sofia, Bulgaria
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Varna, Bulgaria
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Ottawa, Ontario, Canada
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Toronto, Ontario, Canada
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Concepción, Chile
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Santiago, Chile
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Prague, Czechia
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Arhus C, Denmark
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København Ø, Denmark
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Alexandria, Egypt
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BENI SWEF, Egypt
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Cairo, Egypt
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Dakahlia, Egypt
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Bordeaux, France
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Marseille, France
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Paris, France
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Pessac, France
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Pierre-Bénite, France
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Tours, France
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Berlin, Germany
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Essen, Germany
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Freiburg im Breisgau, Germany
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Göttingen, Germany
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Homburg/saar, Germany
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Mainz, Germany
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München, Germany
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Ulm, Germany
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Budapest, Hungary
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Debrecen, Hungary
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Kaposvár, Hungary
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Pécs, Hungary
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Beersheba, Israel
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Haifa, Israel
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Jerusalem, Israel
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Petah Tikva, Israel
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Ramat Gan, Israel
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Tel Aviv, Israel
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Bari, Italy
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Bologna, Italy
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Cagliari, Italy
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Florence, Italy
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Meldola, Italy
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Modena, Italy
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Ravenna, Italy
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Rimini, Italy
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Roma, Italy
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Torino, Italy
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Durango Durango, Mexico
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México, Mexico
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Monterrey, Mexico
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Monterrey Nuevo LEON, Mexico
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San Luis Potosí City, Mexico
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Maastricht, Netherlands
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Nieuwegein, Netherlands
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Auckland, New Zealand
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Christchurch, New Zealand
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Takapuna, New Zealand
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Arequipa, Peru
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Lima, Peru
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Bydgoszcz, Poland
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Chorzów, Poland
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Krakow, Poland
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Lodz, Poland
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Warsaw, Poland
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Wroclaw, Poland
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Braga, Portugal
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Coimbra, Portugal
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Porto, Portugal
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San Juan, PR, Puerto Rico
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Bucharest, Romania
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Chelyabinsk, Russia
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Moscow, Russia
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Petrozavodsk, Russia
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Saint Petersburg, Russia
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Bratislava, Slovakia
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Martin, Slovakia
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Barcelona, Spain
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Girona, Spain
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Madrid, Spain
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Pamplona, Spain
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Salamanca, Spain
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Seville, Spain
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Valencia, Spain
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Linköping, Sweden
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Lund, Sweden
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Solna, Sweden
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Ankara, Turkey (Türkiye)
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Denizli, Turkey (Türkiye)
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Istanbul, Turkey (Türkiye)
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Kayseri, Turkey (Türkiye)
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Samsun, Turkey (Türkiye)
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Birmingham, United Kingdom
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Cardiff, United Kingdom
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Liverpool, United Kingdom
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Manchester, United Kingdom
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Newcastle upon Tyne, United Kingdom
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Southampton, United Kingdom
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Truro, United Kingdom
Related Publications (1)
O'Connor OA, Ozcan M, Jacobsen ED, Roncero JM, Trotman J, Demeter J, Masszi T, Pereira J, Ramchandren R, Beaven A, Caballero D, Horwitz SM, Lennard A, Turgut M, Hamerschlak N, d'Amore FA, Foss F, Kim WS, Leonard JP, Zinzani PL, Chiattone CS, Hsi ED, Trumper L, Liu H, Sheldon-Waniga E, Ullmann CD, Venkatakrishnan K, Leonard EJ, Shustov AR; Lumiere Study Investigators. Randomized Phase III Study of Alisertib or Investigator's Choice (Selected Single Agent) in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma. J Clin Oncol. 2019 Mar 10;37(8):613-623. doi: 10.1200/JCO.18.00899. Epub 2019 Feb 1.
PMID: 30707661DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Medical Monitor
Takeda Oncology
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 28, 2011
First Posted
December 1, 2011
Study Start
June 11, 2012
Primary Completion
June 30, 2015
Study Completion
December 18, 2017
Last Updated
July 31, 2018
Results First Posted
July 31, 2018
Record last verified: 2018-07