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

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ClinicalTrials.gov Identifier: NCT01482962
Recruitment Status : Completed
First Posted : December 1, 2011
Results First Posted : July 31, 2018
Last Update Posted : July 31, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

November 28, 2011
December 1, 2011
May 9, 2018
July 31, 2018
July 31, 2018
June 11, 2012
June 30, 2015   (Final data collection date for primary outcome measure)
  • Overall Response Rate (ORR) Based on Independent Review Committee (IRC) Assessment [ Time Frame: 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.
  • Progression-Free Survival (PFS) Based on IRC Assessment [ Time Frame: 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.
  • Number of patients with overall response [ Time Frame: Change from screening period in response assessed 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 ]
    Overall response rate (ORR) by central review + progression free survival (PFS)
  • Number of patients with PFS [ Time Frame: Change from screening period in response assessed 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 ]
    Based on IRC assessment using a modified IWG (2007) criteria
Complete list of historical versions of study NCT01482962 on ClinicalTrials.gov Archive Site
  • Overall Survival (OS) [ Time Frame: 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.
  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: 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 important event.
  • Number of Participants With Clinically Important Abnormal Laboratory Values Reported as AEs [ Time Frame: 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.
  • Number of Participants With Clinically Important Vital Sign Measurements Reported as AEs [ Time Frame: 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.
  • Complete Response (CR) Rate [ Time Frame: 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.
  • Time to Disease Progression (TTP) [ Time Frame: 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.
  • Duration of Response (DOR) [ Time Frame: 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.
  • Time to Response [ Time Frame: 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.
  • Time to Subsequent Antineoplastic Therapy [ Time Frame: 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.
  • Plasma Concentration-time Data to Contribute to Future Population Pharmacokinetics (PK) Analysis [ Time Frame: Cycle 1, Days 1 and 7; Cycle 2, Day 8; Cycle 3, Day 8; Cycle 4, Day 8. Duration is approximately 4 months. ]
  • 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 [ Time Frame: 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 well-being and a positive change from Baseline indicates improvement.
  • Number of patients with complete response + complete response unconfirmed [ Time Frame: Response assessed 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 ]
  • Number of patients with overall survival [ Time Frame: Patients will be followed for survival for 2 years from date of last patient off study, or death, whichever occurs first. Contacts will be every 4 months. ]
  • Time to disease progression, duration of response, and time to response [ Time Frame: 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. ]
  • Number of adverse events, serious adverse events, assessments of clinical laboratory values and clinically important abnormalities, and vital sign measurements [ Time Frame: For each patient, from screening period to 30 days after last dose of study drug, approximately 1 year ]
    Safety and tolerability of alisertib
  • Time to Subsequent Antineoplastic Therapy [ Time Frame: From date of last study drug to date of subsequent antineoplastic therapy, if required; approximately 3 years ]
  • Plasma concentration-time data to contribute to future population pharmacokinetics (PK) analysis [ Time Frame: Cycle 1, Days 1&7; Cycle 2, Day 8; Cycle 3, Day 8; Cycle 4, Day 8. Duration approximately 4 months. ]
  • Changes in reported symptoms and Quality of Life (QOL) assessment per Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) for functioning and symptoms [ Time Frame: At screening period; Day 1 of each cycle; End of Treatment; Progression Free Survival follow-up. Duration approximately 3 years. ]
Not Provided
Not Provided
 
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
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.

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Relapsed Peripheral T-Cell Lymphoma
  • Refractory Peripheral T-Cell Lymphoma
  • Drug: Alisertib
    Alisertib enteric coated tablets
  • Drug: Pralatrexate
    Pralatrexate IV infusion
  • Drug: Gemcitabine
    Gemcitabine IV infusion
  • Drug: Romidepsin
    Romidepsin IV infusion
  • Experimental: 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).
    Intervention: Drug: Alisertib
  • Active Comparator: 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).
    Interventions:
    • Drug: Pralatrexate
    • Drug: Gemcitabine
    • Drug: Romidepsin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
271
354
December 18, 2017
June 30, 2015   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
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,   Russian Federation,   Slovakia,   Spain,   Sweden,   Turkey,   United Kingdom,   United States
Argentina,   Czech Republic
 
NCT01482962
C14012
2011-003545-18 ( EudraCT Number )
DRKS00004503 ( Registry Identifier: Germany (DRKS) )
NL39566.068.12 ( Registry Identifier: Netherlands (CCMO) )
U1111-1181-8218 ( Registry Identifier: WHO )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Takeda ( Millennium Pharmaceuticals, Inc. )
Millennium Pharmaceuticals, Inc.
Not Provided
Study Director: Medical Monitor Takeda Oncology
Takeda
July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP