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NCT01482962

Alisertib (MLN8237) or Investigator's Choice in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma

Completed Phase 3 Results posted Last updated 31 July 2018
What this trial tests

Phase 3 trial testing Alisertib in Relapsed Peripheral T-Cell Lymphoma in 271 participants. Completed in 18 December 2017.

Timeline
11 June 2012
Primary endpoint
30 June 2015
18 December 2017

Quick facts

Lead sponsorMillennium Pharmaceuticals, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment271
Start date11 June 2012
Primary completion30 June 2015
Estimated completion18 December 2017
Sites151 locations across Italy, Poland, Denmark, New Zealand, Netherlands, Russia, Turkey (Türkiye), Belgium

Drugs / interventions tested

Conditions studied

Sponsor

Millennium Pharmaceuticals, Inc. — full company profile →

Who can join

18 and older, any sex, with Relapsed Peripheral T-Cell Lymphoma or Refractory Peripheral T-Cell Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response Rate (ORR) Based on Independent Review Committee (IRC) Assessment Primary · 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

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.

GroupValue95% CI
Alisertib3324 – 43
Pralatrexate, or Romidepsin, or Gemcitabine4534 – 55
Progression-Free Survival (PFS) Based on IRC Assessment Primary · 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

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.

GroupValue95% CI
Alisertib11583 – 174
Pralatrexate, or Romidepsin, or Gemcitabine10461 – 114
Overall Survival (OS) Secondary · 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)

OS was defined as the time from the date of randomization to the date of death. Participants without documentation of death were censored at the date last known to be alive.

GroupValue95% CI
Alisertib415263 – 514
Pralatrexate, or Romidepsin, or Gemcitabine367258 – 572
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Secondary · First dose to 30 days after last dose of study drug or comparator (Up to 152 Weeks)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. A SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/ birth defect or is a medically

TEAE
GroupValue95% CI
Alisertib136
Pralatrexate, or Romidepsin, or Gemcitabine126
SAE
GroupValue95% CI
Alisertib75
Pralatrexate, or Romidepsin, or Gemcitabine69
Number of Participants With Clinically Important Abnormal Laboratory Values Reported as AEs Secondary · First dose to 30 days after last dose of study drug or comparator (Up to 152 Weeks)

Clinical laboratory tests included chemistry, hematology and urinalysis test. Clinically significant treatment-emergent laboratory abnormalities were reported by the investigator as TEAEs.

Neutrophil Count Decreased
GroupValue95% CI
Alisertib18
Pralatrexate, or Romidepsin, or Gemcitabine14
White Blood Cell Count Decreased
GroupValue95% CI
Alisertib17
Pralatrexate, or Romidepsin, or Gemcitabine10
Lymphocyte Count Decreased
GroupValue95% CI
Alisertib6
Pralatrexate, or Romidepsin, or Gemcitabine5
Monocyte Count Decreased
GroupValue95% CI
Alisertib2
Pralatrexate, or Romidepsin, or Gemcitabine1
Lymphocyte Count Increased
GroupValue95% CI
Alisertib1
Pralatrexate, or Romidepsin, or Gemcitabine0
Monocyte Count Increased
GroupValue95% CI
Alisertib1
Pralatrexate, or Romidepsin, or Gemcitabine0
White Blood Cell Count Increased
GroupValue95% CI
Alisertib1
Pralatrexate, or Romidepsin, or Gemcitabine0
Platelet Count Decreased
GroupValue95% CI
Alisertib15
Pralatrexate, or Romidepsin, or Gemcitabine22
Number of Participants With Clinically Important Vital Sign Measurements Reported as AEs Secondary · First dose to 30 days after last dose of study drug or comparator (Up to 152 Weeks)

Vital signs included blood pressure, heart rate and temperature. Individual clinically significant changes in vital signs were reported by the investigator as TEAEs.

Heart Rate Increased
GroupValue95% CI
Alisertib1
Pralatrexate, or Romidepsin, or Gemcitabine0
Body Temperature Increased
GroupValue95% CI
Alisertib0
Pralatrexate, or Romidepsin, or Gemcitabine1
Hypotension
GroupValue95% CI
Alisertib4
Pralatrexate, or Romidepsin, or Gemcitabine6
Orthostatic Hypotension
GroupValue95% CI
Alisertib2
Pralatrexate, or Romidepsin, or Gemcitabine1
Hypertension
GroupValue95% CI
Alisertib5
Pralatrexate, or Romidepsin, or Gemcitabine7
Pyrexia
GroupValue95% CI
Alisertib48
Pralatrexate, or Romidepsin, or Gemcitabine40
Complete Response (CR) Rate Secondary · 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)

Complete Response (CR) rate is defined as the percentage of participants with CR as assessed by the IRC using IWG criteria (2007 Cheson). CR= Disappearance of all evidence of disease.

GroupValue95% CI
Alisertib1811 – 26
Pralatrexate, or Romidepsin, or Gemcitabine2718 – 37
Time to Disease Progression (TTP) Secondary · 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 progressive disease. Duration is approximately 3 years

Time to Progression (TTP) was defined as the time from the date of randomization to the date of first documentation of PD/relapse.

GroupValue95% CI
Alisertib162114 – 231
Pralatrexate, or Romidepsin, or Gemcitabine116101 – 227
Duration of Response (DOR) Secondary · 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 progressive disease. Duration is approximately 3 years

DOR was defined as the time from the date of first documentation of a PR or better to the date of first documentation of progressive disease (PD)/relapse for responders as assessed by the IRC using IWG criteria. Responders without documentation of PD/relapse were censored at the date of last response assessment that was stable disease (SD) or better.

GroupValue95% CI
Alisertib225125 – NA
Pralatrexate, or Romidepsin, or Gemcitabine172119 – NA
Time to Response Secondary · 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 progressive disease. Duration is approximately 3 years

Time to Response is defined as the time from the date of randomization to the date of first documentation of PR or better.

GroupValue95% CI
Alisertib6257 – 67
Pralatrexate, or Romidepsin, or Gemcitabine6460 – 71
Time to Subsequent Antineoplastic Therapy Secondary · From date of last study drug to date of subsequent antineoplastic therapy, if required; approximately 3 years

Time to subsequent antineoplastic therapy was defined as the time from randomization to the first date of subsequent antineoplastic therapy (excluding transplant). Participants without subsequent antineoplastic therapy were censored at the date of death or last known to be alive.

GroupValue95% CI
Alisertib336201 – 490
Pralatrexate, or Romidepsin, or Gemcitabine233144 – 429
Change Form Baseline in Reported Symptoms and Quality of Life (QoL) Assessment Per Functional Assessment of Cancer Therapy-Lymphoma (FACT-LYM) for Functioning and Symptoms Secondary · Baseline and End of Treatment (EOT) (Up to 152 Weeks)

The FACT-LYM includes the Functional Assessment of Cancer Therapy General Scale (FACT-G) and a 15-item lymphoma-specific subscale (LYM) over the past week. The FACT-G has 27 items that incorporate 4 scales including physical well-being (PWB; 7 items), social/family well-being (SWB, 7 items), emotional well-being (EWB; 6 items), and functional well-being (FWB; 7 items). The combined FACT-LYM instrument consists of a total of a 42 item questionnaire. Each question is answered on a 5- point scale of 0 (not at all) to 4 (very much) for a total possible score of 168. Higher scores indicate better w

Physical Well-Being, EOT
GroupValue95% CI
Alisertib-2.4± 6.21
Pralatrexate, or Romidepsin, or Gemcitabine-1.3± 5.27
Social/Family Well-Being, EOT
GroupValue95% CI
Alisertib-0.3± 4.50
Pralatrexate, or Romidepsin, or Gemcitabine0.0± 4.44
Emotional Well-Being, EOT
GroupValue95% CI
Alisertib-1.4± 4.59
Pralatrexate, or Romidepsin, or Gemcitabine-0.8± 3.93
Functional Well-Being, EOT
GroupValue95% CI
Alisertib-2.4± 5.40
Pralatrexate, or Romidepsin, or Gemcitabine-0.3± 4.79

Adverse events — posted to ClinicalTrials.gov

Time frame: First dose to 30 days after last dose of study drug or comparator (Up to 152 Weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Alisertib
Serious: 75/137 (55%)
Deaths: 11/137
Gemcitabine
Serious: 18/29 (62%)
Deaths: 5/29
Pralatrexate
Serious: 46/76 (61%)
Deaths: 8/76
Romidepsin
Serious: 6/22 (27%)
Deaths: 2/22

Serious adverse events (135 terms)

ReactionSystemAlisertibGemcitabinePralatrexateRomidepsin
Febrile neutropeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
StomatitisGastrointestinal disorders
PneumoniaInfections and infestations
ThrombocytopeniaBlood and lymphatic system disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
Septic shockInfections and infestations
PancytopeniaBlood and lymphatic system disorders
General physical health deteriorationGeneral disorders
VomitingGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Lung infectionInfections and infestations
SepsisInfections and infestations
Skin infectionInfections and infestations
Respiratory tract infectionInfections and infestations
Pseudomonal sepsisInfections and infestations
ErysipelasInfections and infestations
Urinary tract infectionInfections and infestations
NeutropeniaBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
NauseaGastrointestinal disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Other adverse events (81 terms — click to expand)

ReactionSystemAlisertibGemcitabinePralatrexateRomidepsin
AnaemiaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
FatigueGeneral disorders
StomatitisGastrointestinal disorders
AlopeciaSkin and subcutaneous tissue disorders
PyrexiaGeneral disorders
LeukopeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
AstheniaGeneral disorders
Oedema peripheralGeneral disorders
ConstipationGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
VomitingGastrointestinal disorders
Neutrophil count decreasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
Platelet count decreasedInvestigations
White blood cell count decreasedInvestigations
DizzinessNervous system disorders
HeadacheNervous system disorders
SomnolenceNervous system disorders
Pain in extremityMusculoskeletal and connective tissue disorders
LymphopeniaBlood and lymphatic system disorders
Upper respiratory tract infectionInfections and infestations
HypokalaemiaMetabolism and nutrition disorders
DyspepsiaGastrointestinal disorders
Weight decreasedInvestigations
DyspnoeaRespiratory, thoracic and mediastinal disorders
Back painMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
ChillsGeneral disorders
Alanine aminotransferase increasedInvestigations
Blood alkaline phosphatase increasedInvestigations
HypomagnesaemiaMetabolism and nutrition disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Abdominal pain upperGastrointestinal disorders

Most-reported serious reactions: Febrile neutropenia, Pyrexia, Stomatitis, Pneumonia, Thrombocytopenia, Anaemia, Diarrhoea, Septic shock.

Data from ClinicalTrials.gov NCT01482962 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Aurora A kinase (AURKA) in normal and pathological cell division.
    Nikonova AS, Astsaturov I, Serebriiskii IG, Dunbrack RL, et al · · 2013 · cited 368× · PMID 22864622 · DOI 10.1007/s00018-012-1073-7
  2. Therapeutic targeting of "undruggable" MYC.
    Llombart V, Mansour MR. · · 2022 · cited 349× · PMID 34942444 · DOI 10.1016/j.ebiom.2021.103756
  3. Epigenetic regulation in human cancer: the potential role of epi-drug in cancer therapy.
    Lu Y, Chan YT, Tan HY, Li S, et al · · 2020 · cited 318× · PMID 32340605 · DOI 10.1186/s12943-020-01197-3
  4. Patient derived organoids to model rare prostate cancer phenotypes.
    Puca L, Bareja R, Prandi D, Shaw R, et al · · 2018 · cited 289× · PMID 29921838 · DOI 10.1038/s41467-018-04495-z
  5. Phase II study of alisertib, a selective Aurora A kinase inhibitor, in relapsed and refractory aggressive B- and T-cell non-Hodgkin lymphomas.
    Friedberg JW, Mahadevan D, Cebula E, Persky D, et al · · 2014 · cited 166× · PMID 24043741 · DOI 10.1200/jco.2012.46.8793
  6. Randomized Phase III Study of Alisertib or Investigator's Choice (Selected Single Agent) in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma.
    O'Connor OA, Özcan M, Jacobsen ED, Roncero JM, et al · · 2019 · cited 127× · PMID 30707661 · DOI 10.1200/jco.18.00899
  7. The two sides of chromosomal instability: drivers and brakes in cancer.
    Hosea R, Hillary S, Naqvi S, Wu S, et al · · 2024 · cited 102× · PMID 38553459 · DOI 10.1038/s41392-024-01767-7
  8. The roles of histone modifications in tumorigenesis and associated inhibitors in cancer therapy.
    Yang Y, Zhang M, Wang Y. · · 2022 · cited 96× · PMID 39036551 · DOI 10.1016/j.jncc.2022.09.002

Verify or expand the search:

Other trials of Alisertib

Trials testing the same drug.

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Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01482962.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing