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

NCT ID: NCT01482962

Last Updated: 2018-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 271 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-11
• Study Completion Date: 2017-12-18

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.

Conditions

Relapsed Peripheral T-Cell Lymphoma; Refractory Peripheral T-Cell Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Alisertib

Alisertib 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).

Group Type: EXPERIMENTAL

Alisertib

Intervention Type: DRUG

Alisertib enteric coated tablets

Pralatrexate, or Romidepsin, or Gemcitabine

Pralatrexate 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).

Group Type: ACTIVE_COMPARATOR

Pralatrexate

Intervention Type: DRUG

Pralatrexate IV infusion

Gemcitabine

Intervention Type: DRUG

Gemcitabine IV infusion

Romidepsin

Intervention Type: DRUG

Romidepsin IV infusion

Interventions

Alisertib

Alisertib enteric coated tablets

Intervention Type: DRUG

Pralatrexate

Pralatrexate IV infusion

Intervention Type: DRUG

Gemcitabine

Gemcitabine IV infusion

Intervention Type: DRUG

Romidepsin

Romidepsin IV infusion

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Takeda Oncology

Locations

Birmingham, Alabama, United States

La Jolla, California, United States

Orlando, Florida, United States

Tampa, Florida, United States

Indianapolis, Indiana, United States

Iowa City, Iowa, United States

Boston, Massachusetts, United States

Detroit, Michigan, United States

Rochester, Minnesota, United States

Jefferson City, Missouri, United States

St Louis, Missouri, United States

Lebanon, New Hampshire, United States

Hackensack, New Jersey, United States

Buffalo, New York, United States

New York, New York, United States

Syracuse, New York, United States

Durham, North Carolina, United States

Columbus, Ohio, United States

Toledo, Ohio, United States

Charleston, South Carolina, United States

Houston, Texas, United States

Burlington, Vermont, United States

Seattle, Washington, United States

Morgantown, West Virginia, United States

Adelaide, , Australia

Concord, , Australia

Gosford, , Australia

Hobart, , Australia

St Leonards, , Australia

Graz, , Austria

Innsbruck, , Austria

Salzburg, , Austria

Vienna, , Austria

Minsk Didtrict, , Belarus

Vitebsk, , Belarus

Bruges, , Belgium

Brussels, , Belgium

Ghent, , Belgium

Kortrijk, , Belgium

Turnhout, , Belgium

Yvoir, , Belgium

Belo Horizonte, , Brazil

Campianas, , Brazil

Caxias do Sul, , Brazil

Curitiba, , Brazil

Goiânia, , Brazil

Porto Alegre, , Brazil

Porto Alegre/rs, , Brazil

Rio de Janeiro, , Brazil

Salvador, , Brazil

SAO Paulo - SP, , Brazil

São Paulo, , Brazil

Pleven, , Bulgaria

Sofia, , Bulgaria

Varna, , Bulgaria

Ottawa, Ontario, Canada

Toronto, Ontario, Canada

Concepción, , Chile

Santiago, , Chile

Prague, , Czechia

Arhus C, , Denmark

København Ø, , Denmark

Alexandria, , Egypt

BENI SWEF, , Egypt

Cairo, , Egypt

Dakahlia, , Egypt

Bordeaux, , France

Marseille, , France

Paris, , France

Pessac, , France

Pierre-Bénite, , France

Tours, , France

Berlin, , Germany

Essen, , Germany

Freiburg im Breisgau, , Germany

Göttingen, , Germany

Homburg/saar, , Germany

Mainz, , Germany

München, , Germany

Ulm, , Germany

Budapest, , Hungary

Debrecen, , Hungary

Kaposvár, , Hungary

Pécs, , Hungary

Beersheba, , Israel

Haifa, , Israel

Jerusalem, , Israel

Petah Tikva, , Israel

Ramat Gan, , Israel

Tel Aviv, , Israel

Bari, , Italy

Bologna, , Italy

Cagliari, , Italy

Florence, , Italy

Meldola, , Italy

Modena, , Italy

Ravenna, , Italy

Rimini, , Italy

Roma, , Italy

Torino, , Italy

Durango Durango, , Mexico

México, , Mexico

Monterrey, , Mexico

Monterrey Nuevo LEON, , Mexico

San Luis Potosí City, , Mexico

Maastricht, , Netherlands

Nieuwegein, , Netherlands

Auckland, , New Zealand

Christchurch, , New Zealand

Takapuna, , New Zealand

Arequipa, , Peru

Lima, , Peru

Bydgoszcz, , Poland

Chorzów, , Poland

Krakow, , Poland

Lodz, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Braga, , Portugal

Coimbra, , Portugal

Porto, , Portugal

San Juan, PR, Puerto Rico

Bucharest, , Romania

Chelyabinsk, , Russia

Moscow, , Russia

Petrozavodsk, , Russia

Saint Petersburg, , Russia

Bratislava, , Slovakia

Martin, , Slovakia

Barcelona, , Spain

Girona, , Spain

Madrid, , Spain

Pamplona, , Spain

Salamanca, , Spain

Seville, , Spain

Valencia, , Spain

Linköping, , Sweden

Lund, , Sweden

Solna, , Sweden

Ankara, , Turkey (Türkiye)

Denizli, , Turkey (Türkiye)

Istanbul, , Turkey (Türkiye)

Kayseri, , Turkey (Türkiye)

Samsun, , Turkey (Türkiye)

Birmingham, , United Kingdom

Cardiff, , United Kingdom

Liverpool, , United Kingdom

Manchester, , United Kingdom

Newcastle upon Tyne, , United Kingdom

Southampton, , United Kingdom

Truro, , United Kingdom

Countries

United States; Australia; Austria; Belarus; Belgium; Brazil; Bulgaria; Canada; Chile; Czechia; Denmark; Egypt; France; Germany; Hungary; Israel; Italy; Mexico; Netherlands; New Zealand; Peru; Poland; Portugal; Puerto Rico; Romania; Russia; Slovakia; Spain; Sweden; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 30707661 (View on PubMed)

Other Identifiers

2011-003545-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DRKS00004503

Identifier Type: REGISTRY

Identifier Source: secondary_id

NL39566.068.12

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1181-8218

Identifier Type: REGISTRY

Identifier Source: secondary_id

C14012

Identifier Type: -

Identifier Source: org_study_id