ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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. )

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: Relapsed Peripheral T-Cell Lymphoma
Refractory Peripheral T-Cell Lymphoma
Interventions: Drug: Alisertib
Drug: Pralatrexate
Drug: Gemcitabine
Drug: Romidepsin

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants took part in the study at 105 investigative sites in the United States including Puerto Rico, Canada, European Union, Russian Federation, Turkey, Israel, Australia, New Zealand and Latin America from 11 June 2012 to the end of study on 18 December 2017.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with a diagnosis of Relapsed or Refractory Peripheral T-Cell Lymphoma were randomized 1:1 to either alisertib or comparator (investigator’s choice of pralatrexate, romidepsin [USA only], or gemcitabine).

Reporting Groups
  Description
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).
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).

Participant Flow:   Overall Study
    Alisertib   Pralatrexate, or Romidepsin, or Gemcitabine
STARTED   138   133 
Safety Population: Received Study Drug   137   127 
COMPLETED   0   0 
NOT COMPLETED   138   133 
Progressive Disease                65                53 
Unsatisfactory Therapeutic Response                37                23 
Adverse Event                18                22 
Withdrawal by Participant                8                13 
Hematopoietic Stem Cell Transplant                3                9 
Other Reason                1                5 
Study Terminated by Sponsor                5                2 
Did not Receive Study Drug                1                6 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population was defined as all participants who were randomized. The participants were analyzed according to the treatment they were randomized to receive, regardless of any errors of dosing.

Reporting Groups
  Description
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).
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).
Total Total of all reporting groups

Baseline Measures
   Alisertib   Pralatrexate, or Romidepsin, or Gemcitabine   Total 
Overall Participants Analyzed 
[Units: Participants]
 138   133   271 
Age 
[Units: Years]
Mean (Standard Deviation)
 61.1  (12.69)   61.4  (13.16)   61.3  (12.90) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      46  33.3%      47  35.3%      93  34.3% 
Male      92  66.7%      86  64.7%      178  65.7% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
     
Hispanic or Latino      25  18.1%      21  15.8%      46  17.0% 
Not Hispanic or Latino      105  76.1%      107  80.5%      212  78.2% 
Unknown or Not Reported      8   5.8%      5   3.8%      13   4.8% 
Race/Ethnicity, Customized 
[Units: Participants]
     
White   115   114   229 
Black or African American   8   8   16 
Asian   3   2   5 
Other   7   7   14 
Not Reported   5   2   7 
Region of Enrollment 
[Units: Participants]
     
Australia   5   4   9 
Austria   2   2   4 
Belgium   5   3   8 
Brazil   12   10   22 
Bulgaria   0   1   1 
Canada   3   0   3 
Czech Republic   5   2   7 
Denmark   3   2   5 
France   5   3   8 
Germany   6   1   7 
Hungary   9   7   16 
Israel   0   3   3 
Italy   6   6   12 
Mexico   3   1   4 
Netherlands   0   1   1 
New Zealand   3   2   5 
Peru   1   3   4 
Poland   7   3   10 
Portugal   1   1   2 
Puerto Rico   0   1   1 
Romania   2   1   3 
Russia   4   4   8 
Spain   14   11   25 
Sweden   0   3   3 
Turkey   10   11   21 
United Kingdom   3   8   11 
United States   29   39   68 
Height 
[Units: Cm]
Mean (Standard Deviation)
 170.3  (9.80)   168.2  (8.99)   169.3  (9.45) 
Weight 
[Units: Kg]
Mean (Standard Deviation)
 76.85  (17.242)   74.63  (19.601)   75.76  (18.437) 
Body Surface Area (BSA) [1] 
[Units: M^2]
Mean (Standard Deviation)
 1.897  (0.2465)   1.855  (0.2562)   1.877  (0.2517) 
[1] Body surface area (m^2)=square root [height (cm)*weight (kg)/3600].


  Outcome Measures

1.  Primary:   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 ]

2.  Primary:   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 ]

3.  Secondary:   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) ]

4.  Secondary:   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) ]

5.  Secondary:   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) ]

6.  Secondary:   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) ]

7.  Secondary:   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) ]

8.  Secondary:   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 ]

9.  Secondary:   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 ]

10.  Secondary:   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 ]

11.  Secondary:   Time to Subsequent Antineoplastic Therapy   [ Time Frame: From date of last study drug to date of subsequent antineoplastic therapy, if required; approximately 3 years ]

12.  Secondary:   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. ]

13.  Secondary:   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) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Director
Organization: Takeda
phone: +1-877-825-3327
e-mail: trialdisclosures@takeda.com



Responsible Party: Takeda ( 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 Submitted: November 28, 2011
First Posted: December 1, 2011
Results First Submitted: May 9, 2018
Results First Posted: July 31, 2018
Last Update Posted: July 31, 2018