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A Phase II Clinical Trial of PXD101 in Patients With Recurrent or Refractory Cutaneous and Peripheral T-Cell Lymphomas (PXD101-CLN-6)

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ClinicalTrials.gov Identifier: NCT00274651
Recruitment Status : Terminated (Enrollment stopped prior to reaching expected number of patients, study had accumulated sufficient data to allow a registration study in PTCL (PXD101-CLN-19))
First Posted : January 11, 2006
Results First Posted : October 27, 2014
Last Update Posted : July 28, 2015
Sponsor:
Information provided by (Responsible Party):
Onxeo

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Cutaneous T-Cell Lymphoma
Peripheral T-Cell Lymphoma
Non-Hodgkin's Lymphoma
Intervention Drug: belinostat
Enrollment 53
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm A (CTCL, ITT Population) Arm B (PTCL, ITT Population)
Hide Arm/Group Description PXD101 1000 mg/m2 once daily for 5 days every 21 days PXD101 1000 mg/m2 once daily for 5 days every 21 days
Period Title: Overall Study
Started 29 24
Completed 1 4
Not Completed 28 20
Reason Not Completed
Adverse Event             6             3
Lack of Efficacy             13             6
Death             1             3
Withdrawal by Subject             0             1
Physician Decision             8             7
Arm/Group Title CTCL (ITT Population) PTCL (ITT Population) Total
Hide Arm/Group Description

CTCL patients will receive 1000 mg/m2 of PXD101 IV

belinostat: 1000 mg/m2 for 5 days every 21 days; IV

PTCL patients will receive 1000 mg/m2 of PXD101 IV

belinostat: 1000 mg/m2 for 5 days every 21 days; IV

Total of all reporting groups
Overall Number of Baseline Participants 29 24 53
Hide Baseline Analysis Population Description
Patients received PXD101, 1000 mg/m2/day over 30 minutes days 1-5 of a 21-day cycle. Patients with OR or stable disease were permitted to continue with PXD101 for up to 8 cycles or until progressive disease. Patients with PR or SD could continue therapy beyond 8 cycles until progression in consultation with Investigators and Sponsor.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 29 participants 24 participants 53 participants
64.1  (13.4) 58.8  (15.9) 61.7  (14.7)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 24 participants 53 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
12
  41.4%
12
  50.0%
24
  45.3%
>=65 years
17
  58.6%
12
  50.0%
29
  54.7%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 24 participants 53 participants
Female
15
  51.7%
7
  29.2%
22
  41.5%
Male
14
  48.3%
17
  70.8%
31
  58.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 29 participants 24 participants 53 participants
United States 22 17 39
France 2 0 2
Israel 2 1 3
Thailand 2 6 8
Germany 1 0 1
1.Primary Outcome
Title Objective Response Rate in Patients With Recurrent or Refractory Cutaneous T-cell Lymphoma (CTCL)
Hide Description Tumor response was assessed using Cheson (Cheson 2007) and SWAT criteria. The SWAT score represents the product of the percentage total body surface area (TBSA) involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor.
Time Frame throughout the study, or for a maximum of 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
At termination OR was noted in 1/13 patients (Simon Stage 1). With 29 patients in the CTCL arm the demand for expansion to Simon Stage 2 lacked 5 patients and the study was stopped. Instead OR was done as secondary efficacy analysis (ITT and PP (per protocol)) with OR calculated without accounting for Simon design and with 95% confidence intervals
Arm/Group Title Arm A (CTCL, ITT Population)
Hide Arm/Group Description:

CTCL patients will receive 1000 mg/m2 of PXD101 IV

belinostat: 1000 mg/m2 for 5 days every 21 days; IV

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
2.Primary Outcome
Title Objective Response Rate in Patients With Recurrent or Refractory Peripheral T-cell Lymphoma (PTCL))
Hide Description Tumor response was assessed using the revised criteria of Cheson (Cheson 2007).Tumor assessments were done using conventional radiographic methods, e.g. CT or CT/PET.
Time Frame throughout the study, or for a maximum of 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Primary efficacy analysis is based on the ITT analysis set, where the OR are calculated, and the proportion ± 80% CI (confidence interval) specified by Koyama & Chen (2008) are presented
Arm/Group Title PTCL (ITT Population)
Hide Arm/Group Description:

PTCL patients will receive 1000 mg/m2 of PXD101 IV

belinostat: 1000 mg/m2 for 5 days every 21 days; IV

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: percentage of patients with OR
25
3.Secondary Outcome
Title Time to Progression
Hide Description Time to progression was defined as the interval between the first date of treatment and the first notation of disease progression.
Time Frame throughout the study, or for a maximum of 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Time to Progression (ITT population) was estimated using the Kaplan-Meier method for CTCL and PTCL arms. As progression was not observed in six patients in Arm A and 10 patients in Arm B, a total of 37 patients progressed, and the the median time to progression and the full range (days) are presented.
Arm/Group Title Arm A (CTCL, ITT Population) Arm B (PTCL, ITT Population)
Hide Arm/Group Description:

CTCL patients will receive 1000 mg/m2 of PXD101 IV

belinostat: 1000 mg/m2 for 5 days every 21 days; IV

PTCL patients will receive 1000 mg/m2 of PXD101 IV

belinostat: 1000 mg/m2 for 5 days every 21 days; IV

Overall Number of Participants Analyzed 23 14
Median (Full Range)
Unit of Measure: Days
43
(15 to 304)
82
(9 to 890)
4.Secondary Outcome
Title Time to Response
Hide Description Time to response was defined as the interval between the first date of treatment and the first notation of response.
Time Frame throughout the study, or for a maximum of 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Time to response (ITT population) was estimated using the Kaplan-Meier method for CTCL and PTCL arms. For 4 patients with CTCL and 6 patients with PTCL, response was recorded. The median time to response and the full range (days) are presented.
Arm/Group Title Arm A (CTCL, ITT Population) Arm B (PTCL, ITT Population)
Hide Arm/Group Description:

CTCL patients will receive 1000 mg/m2 of PXD101 IV

belinostat: 1000 mg/m2 for 5 days every 21 days; IV

PTCL patients will receive 1000 mg/m2 of PXD101 IV

belinostat: 1000 mg/m2 for 5 days every 21 days; IV

Overall Number of Participants Analyzed 4 6
Median (Full Range)
Unit of Measure: Days
40
(15 to 176)
100
(9 to 431)
5.Secondary Outcome
Title Duration of Response
Hide Description Duration of response was defined as the time from first notation of response until the time of first notation of disease progression.
Time Frame throughout the study, or for a maximum of 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Duration of response (ITT population) was estimated by Kaplan-Meier method for CTCL/PTCL arms. 2 CTCL and 2 PTCL patients did not progress and were censored. Median duration of response and full range (days) are presented for 2 patients with CTCL and 4 patients with PTCL. The 2 CTCL patients being evaluable had response durations of 56 and 129 days
Arm/Group Title Arm A (CTCL, ITT Population) Arm B (PTCL, ITT Population)
Hide Arm/Group Description:

CTCL patients will receive 1000 mg/m2 of PXD101 IV

belinostat: 1000 mg/m2 for 5 days every 21 days; IV

PTCL patients will receive 1000 mg/m2 of PXD101 IV

belinostat: 1000 mg/m2 for 5 days every 21 days; IV

Overall Number of Participants Analyzed 2 4
Median (Full Range)
Unit of Measure: Days
83
(56 to 129)
109
(7 to 460)
6.Post-Hoc Outcome
Title Objective Response Rate in Patients With Recurrent or Refractory Cutaneous T-cell Lymphoma (CTCL)
Hide Description Tumor response was assessed using Cheson (Cheson 2007) and SWAT criteria. The SWAT score represents the product of the percentage total body surface area (TBSA) involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor.
Time Frame throughout the study, or for a maximum of 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
At termination OR was noted in 1/13 patients (Simon Stage 1). With 29 patients in the CTCL arm the demand for expansion to Simon Stage 2 lacked 5 patients and the study was stopped. Instead OR was done as secondary efficacy analysis (ITT and PP (per protocol)) with OR calculated without accounting for Simon design and with 95% confidence intervals
Arm/Group Title Arm A (CTCL, ITT Population)
Hide Arm/Group Description:

CTCL patients will receive 1000 mg/m2 of PXD101 IV

belinostat: 1000 mg/m2 for 5 days every 21 days; IV

Overall Number of Participants Analyzed 29
Measure Type: Number
Unit of Measure: participants
4
Time Frame Throughout study, up to 4 weeks after last drug administration
Adverse Event Reporting Description Follow-up of the AE (adverse event) was required during the study and after completion, withdrawal or discontinuation of the study if the event was still ongoing. The Investigator was to continuously monitor patients with AEs until the event had returned to baseline or ≤ Grade 1 or until the patient started another type of antineoplastic therapy.
 
Arm/Group Title Arm A (CTCL, ITT Population) Arm B (PTCL, ITT Population)
Hide Arm/Group Description

CTCL patients will receive 1000 mg/m2 of PXD101 IV

belinostat: 1000 mg/m2 for 5 days every 21 days; IV

PTCL patients will receive 1000 mg/m2 of PXD101 IV

belinostat: 1000 mg/m2 for 5 days every 21 days; IV

All-Cause Mortality
Arm A (CTCL, ITT Population) Arm B (PTCL, ITT Population)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Arm A (CTCL, ITT Population) Arm B (PTCL, ITT Population)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/29 (24.14%)      8/24 (33.33%)    
Blood and lymphatic system disorders     
Thrombocytopenia  1  0/29 (0.00%)  0 1/24 (4.17%)  1
Cardiac disorders     
Ventricular fibrillation  1  0/29 (0.00%)  0 1/24 (4.17%)  1
Gastrointestinal disorders     
Abdominal pain  1  1/29 (3.45%)  1 1/24 (4.17%)  3
Ileus paralytic  1  0/29 (0.00%)  0 1/24 (4.17%)  1
General disorders     
Disease progression  1  1/29 (3.45%)  1 1/24 (4.17%)  1
Gait disturbance  1  1/29 (3.45%)  1 0/24 (0.00%)  0
Oedema peripheral  1  1/29 (3.45%)  1 0/24 (0.00%)  0
Pyrexia  1  0/29 (0.00%)  0 1/24 (4.17%)  1
Infections and infestations     
Staphylococcal skin infection  1  1/29 (3.45%)  1 0/24 (0.00%)  0
Implant site abscess  1  1/29 (3.45%)  1 0/24 (0.00%)  0
Sepsis  1  2/29 (6.90%)  2 0/24 (0.00%)  0
Pneumonia  1  0/29 (0.00%)  0 1/24 (4.17%)  1
Catheter related infection  1  0/29 (0.00%)  0 1/24 (4.17%)  1
Upper respiratory tract infection  1  0/29 (0.00%)  0 1/24 (4.17%)  1
Metabolism and nutrition disorders     
Dehydration  1  1/29 (3.45%)  1 0/24 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Muscular weakness  1  0/29 (0.00%)  0 1/24 (4.17%)  1
Nervous system disorders     
Apraxia  1  1/29 (3.45%)  1 0/24 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pneumonitis  1  0/29 (0.00%)  0 1/24 (4.17%)  1
Vascular disorders     
Jugular vein thrombosis  1  1/29 (3.45%)  1 0/24 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm A (CTCL, ITT Population) Arm B (PTCL, ITT Population)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   29/29 (100.00%)      23/24 (95.83%)    
Blood and lymphatic system disorders     
Eosinophilia  1  2/29 (6.90%)  3 1/24 (4.17%)  1
Lymphadenopathy  1  2/29 (6.90%)  3 1/24 (4.17%)  1
Thrombocytopenia  1  0/29 (0.00%)  0 3/24 (12.50%)  4
Anaemia  1  0/29 (0.00%)  0 2/24 (8.33%)  2
Cardiac disorders     
Tachycardia  1  1/29 (3.45%)  2 3/24 (12.50%)  6
Ear and labyrinth disorders     
Vertigo  1  2/29 (6.90%)  3 0/24 (0.00%)  0
Gastrointestinal disorders     
Nausea  1  17/29 (58.62%)  29 16/24 (66.67%)  32
Constipation  1  5/29 (17.24%)  5 9/24 (37.50%)  10
Vomiting  1  8/29 (27.59%)  14 6/24 (25.00%)  19
Diarrhoea  1  4/29 (13.79%)  4 5/24 (20.83%)  10
Dyspepsia  1  3/29 (10.34%)  3 3/24 (12.50%)  4
Abdominal pain  1  3/29 (10.34%)  3 2/24 (8.33%)  4
Abdominal discomfort  1  0/29 (0.00%)  0 3/24 (12.50%)  4
Gastrooesophageal reflux disease  1  1/29 (3.45%)  1 2/24 (8.33%)  2
Abdominal distension  1  0/29 (0.00%)  0 2/24 (8.33%)  3
Stomatitis  1  0/29 (0.00%)  0 2/24 (8.33%)  2
General disorders     
Fatigue  1  6/29 (20.69%)  11 8/24 (33.33%)  11
Pyrexia  1  5/29 (17.24%)  9 6/24 (25.00%)  16
Infusion site pain  1  6/29 (20.69%)  6 3/24 (12.50%)  3
Oedema peripheral  1  6/29 (20.69%)  7 1/24 (4.17%)  1
Injection site reaction  1  0/29 (0.00%)  0 5/24 (20.83%)  9
Asthenia  1  1/29 (3.45%)  1 2/24 (8.33%)  2
Chest pain  1  3/29 (10.34%)  3 0/24 (0.00%)  0
Chills  1  3/29 (10.34%)  3 0/24 (0.00%)  0
Disease progression  1  1/29 (3.45%)  1 2/24 (8.33%)  2
Gait disturbance  1  3/29 (10.34%)  3 0/24 (0.00%)  0
Oedema  1  1/29 (3.45%)  1 2/24 (8.33%)  2
Mucosal inflammation  1  2/29 (6.90%)  2 0/24 (0.00%)  0
Immune system disorders     
Hypersensitivity  1  0/29 (0.00%)  0 2/24 (8.33%)  2
Infections and infestations     
Upper respiratory tract infection  1  3/29 (10.34%)  3 2/24 (8.33%)  2
Cellulitis  1  2/29 (6.90%)  2 2/24 (8.33%)  2
Herpes simplex  1  2/29 (6.90%)  2 0/24 (0.00%)  0
Pneumonia  1  0/29 (0.00%)  0 2/24 (8.33%)  2
Sepsis  1  2/29 (6.90%)  2 0/24 (0.00%)  0
Skin infection  1  2/29 (6.90%)  2 0/24 (0.00%)  0
Tinea pedis  1  2/29 (6.90%)  2 0/24 (0.00%)  0
Investigations     
Alanine aminotransferase increased  1  2/29 (6.90%)  2 2/24 (8.33%)  3
Aspartate aminotransferase increased  1  2/29 (6.90%)  2 2/24 (8.33%)  2
Blood alkaline phosphatase increased  1  1/29 (3.45%)  1 3/24 (12.50%)  3
Blood lactate dehydrogenase increased  1  3/29 (10.34%)  3 0/24 (0.00%)  0
Blood creatinine increased  1  2/29 (6.90%)  3 0/24 (0.00%)  0
Blood magnesium decreased  1  0/29 (0.00%)  0 2/24 (8.33%)  2
Blood uric acid increased  1  2/29 (6.90%)  2 0/24 (0.00%)  0
Body temperature increased  1  2/29 (6.90%)  2 0/24 (0.00%)  0
Metabolism and nutrition disorders     
Anorexia  1  3/29 (10.34%)  3 5/24 (20.83%)  5
Hypokalaemia  1  3/29 (10.34%)  5 4/24 (16.67%)  9
Dehydration  1  1/29 (3.45%)  1 4/24 (16.67%)  4
Hypoalbuminaemia  1  1/29 (3.45%)  1 2/24 (8.33%)  2
Hypomagnesaemia  1  2/29 (6.90%)  2 0/24 (0.00%)  0
Decreased appetite  1  0/29 (0.00%)  0 2/24 (8.33%)  2
Musculoskeletal and connective tissue disorders     
Pain in extremity  1  5/29 (17.24%)  6 5/24 (20.83%)  5
Myalgia  1  2/29 (6.90%)  3 3/24 (12.50%)  4
Muscular weakness  1  2/29 (6.90%)  2 2/24 (8.33%)  2
Back pain  1  2/29 (6.90%)  2 1/24 (4.17%)  1
Muscle spams  1  2/29 (6.90%)  3 1/24 (4.17%)  2
Neck pain  1  2/29 (6.90%)  2 0/24 (0.00%)  0
Nervous system disorders     
Dizziness  1  6/29 (20.69%)  7 5/24 (20.83%)  8
Headache  1  6/29 (20.69%)  6 1/24 (4.17%)  1
Dysgeusia  1  3/29 (10.34%)  3 1/24 (4.17%)  1
Hypoparaesthesia  1  3/29 (10.34%)  3 0/24 (0.00%)  0
Psychiatric disorders     
Confusional state  1  2/29 (6.90%)  2 2/24 (8.33%)  2
Insomnia  1  1/29 (3.45%)  1 2/24 (8.33%)  4
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  4/29 (13.79%)  4 2/24 (8.33%)  3
Cough  1  3/29 (10.34%)  3 2/24 (8.33%)  2
Hiccups  1  0/29 (0.00%)  0 2/24 (8.33%)  2
Nasal congestion  1  0/29 (0.00%)  0 2/24 (8.33%)  2
Skin and subcutaneous tissue disorders     
Pruritus  1  7/29 (24.14%)  8 2/24 (8.33%)  2
Rash  1  4/29 (13.79%)  5 3/24 (12.50%)  3
Skin exfoliation  1  4/29 (13.79%)  4 0/24 (0.00%)  0
Rash maculo-papular  1  0/29 (0.00%)  0 2/24 (8.33%)  2
Vascular disorders     
Flushing  1  1/29 (3.45%)  1 4/24 (16.67%)  4
Phlebitis  1  3/29 (10.34%)  3 1/24 (4.17%)  1
Hypotension  1  2/29 (6.90%)  2 0/24 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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.
Results Point of Contact
Name/Title: PRS Admnistrator Gunilla Emanuelson
Organization: Topotarget A/S
Phone: +45 39 17 83 92
Responsible Party: Onxeo
ClinicalTrials.gov Identifier: NCT00274651     History of Changes
Other Study ID Numbers: PXD101-CLN-6
First Submitted: January 10, 2006
First Posted: January 11, 2006
Results First Submitted: June 30, 2014
Results First Posted: October 27, 2014
Last Update Posted: July 28, 2015