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Trial record 1 of 1 for:    NCT 01482962
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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
Last Update Posted : April 26, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

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.

Condition or disease Intervention/treatment Phase
Relapsed Peripheral T-Cell Lymphoma Refractory Peripheral T-Cell Lymphoma Drug: Alisertib Drug: Pralatrexate Drug: Gemcitabine Drug: Romidepsin Phase 3

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 271 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 11, 2012
Actual Primary Completion Date : June 30, 2015
Actual Study Completion Date : December 18, 2017


Arm Intervention/treatment
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).
Drug: Alisertib
Alisertib enteric coated tablets
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).
Drug: Pralatrexate
Pralatrexate IV infusion
Drug: Gemcitabine
Gemcitabine IV infusion
Drug: Romidepsin
Romidepsin IV infusion



Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Participants were followed for survival for 2 years from date of last participant off study, 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.

  2. 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.

  3. 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.

  4. 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.

  5. Complete Response Rate (CRR) [ 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 Rate is defined as the percentage of participants with complete response (CR) as assessed by the IRC using IWG criteria. CR= Disappearance of all evidence of disease.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Ctrough: Observed Concentration at the End of a Dosing Interval for Alisertib [ Time Frame: Cycle 1, Day 1 and 7 pre-dose ]
  11. 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 scale of 4 for a total possible score. Higher scores indicate better well-being and a positive change from Baseline indicates improvement.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01482962


  Show 152 Study Locations
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Takeda Oncology

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01482962     History of Changes
Other Study ID Numbers: C14012
2011-003545-18 ( EudraCT Number )
DRKS00004503 ( Registry Identifier: Germany (DRKS) )
NL39566.068.12 ( Registry Identifier: Netherlands (CCMO) )
U1111-1181-8218 ( Registry Identifier: WHO )
First Posted: December 1, 2011    Key Record Dates
Last Update Posted: April 26, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
Drug Therapy

Additional relevant MeSH terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Gemcitabine
Aminopterin
Romidepsin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Folic Acid Antagonists