Clinical trial NCT01482962: Alisertib (MLN8237) or Investigator's Choice in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Relapsed Peripheral T-Cell Lymphoma
Refractory Peripheral T-Cell Lymphoma
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-12-01
Enrollment: 271
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: The drug being tested in this study was Alisertib. Alisertib was tested to treat people who have relapsed/refractory peripheral T-cell lymphoma (PTCL).

This study evaluated alisertib for the improvement in overall response rate (ORR) compared with single-agent treatment, as selected by the investigator from the offered options of pralatrexate, romidepsin (US only), or gemcitabine, in participants with relapsed or refractory PTCL.

The study enrolled 271 patients. Participants were randomized (1:1) to one of 2 treatment arms:

* Alisertib
* Investigator's choice (Pralatrexate, Romidepsin, or Gemcitabine)

This multi-center trial was conducted worldwide. The overall time to participate in this study was approximately 5 years. Participants made multiple visits to the clinic, and then were contacted by telephone up to 42-months after the last participant was randomized, or until death, for follow-up assessment.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria

* 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
* Serious medical or psychiatric illness or laboratory abnormality that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol

Primary outcomes:
measure: Overall Response Rate (ORR) Based on Independent Review Committee (IRC) Assessment
timeFrame: 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
measure: Progression-Free Survival (PFS) Based on IRC Assessment
timeFrame: 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:
measure: Overall Survival (OS)
timeFrame: 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)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: First dose to 30 days after last dose of study drug or comparator (Up to 152 Weeks)
measure: Number of Participants With Clinically Important Abnormal Laboratory Values Reported as AEs
timeFrame: First dose to 30 days after last dose of study drug or comparator (Up to 152 Weeks)
measure: Number of Participants With Clinically Important Vital Sign Measurements Reported as AEs
timeFrame: First dose to 30 days after last dose of study drug or comparator (Up to 152 Weeks)
measure: Complete Response (CR) Rate
timeFrame: 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)
measure: Time to Disease Progression (TTP)
timeFrame: 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
measure: Duration of Response (DOR)
timeFrame: 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
measure: Time to Response
timeFrame: 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
measure: Time to Subsequent Antineoplastic Therapy
timeFrame: From date of last study drug to date of subsequent antineoplastic therapy, if required; approximately 3 years
measure: Plasma Concentration-time Data to Contribute to Future Population Pharmacokinetics (PK) Analysis
timeFrame: Cycle 1, Days 1 and 7; Cycle 2, Day 8; Cycle 3, Day 8; Cycle 4, Day 8. Duration is approximately 4 months.
measure: 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
timeFrame: Baseline and End of Treatment (EOT) (Up to 152 Weeks)
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: La Jolla
country: United States
state: California
city: Orlando
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state: Florida
city: Tampa
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state: Florida
city: Indianapolis
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state: Indiana
city: Iowa City
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state: Iowa
city: Boston
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state: Massachusetts
city: Detroit
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state: Michigan
city: Rochester
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state: Minnesota
city: Jefferson City
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state: Missouri
city: Saint Louis
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state: Missouri
city: Lebanon
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state: New Hampshire
city: Hackensack
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state: New Jersey
city: Buffalo
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state: New York
city: New York
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state: New York
city: Syracuse
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state: New York
city: Durham
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state: North Carolina
city: Columbus
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state: Ohio
city: Toledo
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state: Ohio
city: Charleston
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state: South Carolina
city: Houston
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state: Texas
city: Burlington
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state: Vermont
city: Seattle
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state: Washington
city: Morgantown
country: United States
state: West Virginia
city: Adelaide
country: Australia
city: Concord
country: Australia
city: Gosford
country: Australia
city: Hobart
country: Australia
city: St Leonards
country: Australia
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Salzburg
country: Austria
city: Wien
country: Austria
city: Minsk Didtrict
country: Belarus
city: Vitebsk
country: Belarus
city: Brugge
country: Belgium
city: Brussels
country: Belgium
city: Gent
country: Belgium
city: Kortrijk
country: Belgium
city: Turnhout
country: Belgium
city: Yvoir
country: Belgium
city: Belo Horizonte
country: Brazil
city: Campianas
country: Brazil
city: Caxias Do Sul
country: Brazil
city: Curitiba
country: Brazil
city: Goiania
country: Brazil
city: Porto Alegre/rs
country: Brazil
city: Porto Alegre
country: Brazil
city: Rio de Janeiro
country: Brazil
city: Salvador
country: Brazil
city: SAO Paulo - SP
country: Brazil
city: Sao Paulo
country: Brazil
city: Pleven
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Concepcion
country: Chile
city: Santiago
country: Chile
city: Praha 2
country: Czechia
city: Arhus C
country: Denmark
city: Kobenhavn O
country: Denmark
city: Alexandria
country: Egypt
city: Beni Swef
country: Egypt
city: Cairo
country: Egypt
city: Dakahlia
country: Egypt
city: Bordeaux
country: France
city: Marseille
country: France
city: Paris
country: France
city: Pessac
country: France
city: Pierre Benite
country: France
city: Tours
country: France
city: Berlin
country: Germany
city: Essen
country: Germany
city: Freiburg
country: Germany
city: Goettingen
country: Germany
city: Homburg/saar
country: Germany
city: Mainz
country: Germany
city: Muenchen
country: Germany
city: Munchen
country: Germany
city: ULM
country: Germany
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Kaposvar
country: Hungary
city: Pecs
country: Hungary
city: Beer-sheva
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Petach Tikva
country: Israel
city: Ramat-gan
country: Israel
city: Tel Aviv
country: Israel
city: Bari
country: Italy
city: Bologna
country: Italy
city: Cagliari
country: Italy
city: Firenze
country: Italy
city: Meldola
country: Italy
city: Modena
country: Italy
city: Ravenna
country: Italy
city: Rimini
country: Italy
city: Roma
country: Italy
city: Torino
country: Italy
city: Durango Durango
country: Mexico
city: Mexico
country: Mexico
city: Monterrey Nuevo LEON
country: Mexico
city: Monterrey
country: Mexico
city: San Luis Potosi
country: Mexico
city: Maastricht
country: Netherlands
city: Nieuwegein
country: Netherlands
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: Takapuna
country: New Zealand
city: Arequipa
country: Peru
city: Lima
country: Peru
city: Bydgoszcz
country: Poland
city: Chorzow
country: Poland
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Braga
country: Portugal
city: Coimbra
country: Portugal
city: Porto
country: Portugal
city: San Juan
country: Puerto Rico
city: Bucuresti
country: Romania
city: Chelyabinsk
country: Russian Federation
city: Moscow
country: Russian Federation
city: Petrozavodsk
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Bratislava
country: Slovakia
city: Martin
country: Slovakia
city: Barcelona
country: Spain
city: Girona
country: Spain
city: Madrid
country: Spain
city: Pamplona
country: Spain
city: Salamanca
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Linkoping
country: Sweden
city: Lund
country: Sweden
city: Solna
country: Sweden
city: Ankara
country: Turkey
city: Denizli
country: Turkey
city: Istanbul
country: Turkey
city: Kayseri
country: Turkey
city: Samsun
country: Turkey
city: Birmingham
country: United Kingdom
city: Cardiff
country: United Kingdom
city: Liverpool
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Southampton
country: United Kingdom
city: Truro
country: United Kingdom
Study officials:
affiliation: Takeda Oncology
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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.