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Trial record 18 of 19 for:    pralatrexate AND PTCL

Combination Chemotherapy and Pralatrexate as First-Line Therapy in Treating Patients With Non-Hodgkin Lymphoma

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ClinicalTrials.gov Identifier: NCT01336933
Recruitment Status : Completed
First Posted : April 18, 2011
Results First Posted : June 25, 2018
Last Update Posted : June 25, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Spectrum Pharmaceuticals, Inc
Information provided by (Responsible Party):
Julie M Vose, MD, University of Nebraska

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Hepatosplenic T-cell Lymphoma
Peripheral T-cell Lymphoma
Interventions Drug: prednisone
Drug: cyclophosphamide
Drug: etoposide
Drug: Vincristine
Drug: pralatrexate
Other: laboratory biomarker analysis
Genetic: comparative genomic hybridization
Genetic: gene expression analysis
Genetic: nucleic acid sequencing
Genetic: mutation analysis
Other: immunohistochemistry staining method
Genetic: microarray analysis
Genetic: RNA analysis
Enrollment 34
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Chemotherapy and Enzyme Inhibitor Therapy
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"A" Treatment: Cyclophosphamide,Etoposide, Vincristine and Prednisone (CEOP) "B" Treatment: Pralatrexate (P)

“A” cycles (CEOP) of the treatment regimen are 14 days, followed by “ B” cycles (P) which are 21 days, followed by 7 days of rest for a total of 42 days per course, unless criteria are met for stopping or holding treatment or to a maximum of 6 courses.

Patients with Complete Response (CR) or Partial Response (PR), per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation.

Period Title: Overall Study
Started 34
Completed 33
Not Completed 1
Arm/Group Title Treatment (Chemotherapy and Enzyme Inhibitor Therapy)
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Cyclophosphamide and vincristine sulfate by IV on day 1, etoposide IV on days 1-3 or by mouth (PO), once a day (QD) on days 2-3, and prednisone PO QD on days 1-5 (CEOP administration). Patients also receive pralatrexate IV over 3-5 minutes on days 15, 22, and 29 (P administration). Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients with CR or PR, per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation.

prednisone: Given PO

cyclophosphamide: Given IV

etoposide: Given PO or IV

vincristine sulfate: Given IV

pralatrexate: Given IV

laboratory biomarker analysis: Correlative studies

comparative genomic hybridization: Correlative studies

gene expression analysis: Correlative studies

nucleic acid sequencing: Correlative studies

mutation analysis

Overall Number of Baseline Participants 33
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 33 participants
62
(27 to 83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants
Female
9
  27.3%
Male
24
  72.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
30
  90.9%
Unknown or Not Reported
3
   9.1%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 33 participants
33
 100.0%
1.Primary Outcome
Title Complete Response Rate of Cyclophosphamide, Etoposide, Vincristine and Prednisone (CEOP) and Pralatrexate (P) Treatment
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Complete Response Rate (CR) was reported at the end of the CEOP-P (6 courses for patients not receiving transplant and 4–6 courses for patients receiving transplant). Response assessment was performed by computerized tomography (CT) or positron emission tomography (PET)/CT based on the investigator’s preference after cycles 2, 4 and 6. Response was assessed by the treating physician according to the Cheson Revised response criteria (Cheson et al,, 2007) or International Harmonization Project criteria (Cheson, 2007), based on imaging modality used.

Complete Response Definition: Disappearance of all evidence of disease Nodal Masses: (a) [18F]fluorodeoxyglucose(FDG)-avid or PET positive prior to therapy; mass of any size permitted if PETnegative (b) Variably FDG-avid or PET negative; regression to normal size on CT Spleen, Liver: Not palpable, nodules disappeared Bone Marrow: Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry should be negative

Time Frame 168 days - 252 days (4-6 courses; 42 days per course)
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[Not Specified]
Arm/Group Title Treatment (Chemotherapy and Enzyme Inhibitor Therapy)
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Patients receive cyclophosphamide IV and vincristine sulfate IV on day 1, etoposide IV on days 1-3 or PO QD on days 2-3, and prednisone PO QD on days 1-5 (CEOP administration). Patients also receive pralatrexate IV over 3-5 minutes on days 15, 22, and 29 (P administration). Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients with CR or PR, per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation.

prednisone: Given PO

cyclophosphamide: Given IV

etoposide: Given PO or IV

vincristine sulfate: Given IV

pralatrexate: Given IV

laboratory biomarker analysis: Correlative studies

comparative genomic hybridization: Correlative studies

gene expression analysis: Correlative studies

nucleic acid sequencing: Correlative studies

mutation analysis: Correlative studies

Overall Number of Participants Analyzed 33
Measure Type: Number
Unit of Measure: percentage of participants analyzed
52
2.Secondary Outcome
Title Overall Response Rates (ORR)= (Complete Response Rates (CR) + Partial Response Rates (PR))
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Every patient who fulfills all aspects of patient eligibility who receives at least 2 complete courses of chemotherapy will be evaluable for the response endpoint. Response rates will be descriptively summarized using percentages and 95% confidence intervals.

Complete Response Definition: Defined in Primary Objective Partial Response Definition: Regression of measurable disease and no new sites, Nodal Masses: > 50% decrease in sum of the product of the diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes

  1. FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site
  2. Variably FDG-avid or PET negative; regression on CT Spleen, Liver:> 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen Bone Marrow: Irrelevant if positive prior to therapy; cell type should be specified
Time Frame 2 years
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Chemotherapy and Enzyme Inhibitor Therapy)
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Patients receive cyclophosphamide IV and vincristine sulfate IV on day 1, etoposide IV on days 1-3 or PO QD on days 2-3, and prednisone PO QD on days 1-5 (CEOP administration). Patients also receive pralatrexate IV over 3-5 minutes on days 15, 22, and 29 (P administration). Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients with CR or PR, per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation.

prednisone: Given PO

cyclophosphamide: Given IV

etoposide: Given PO or IV

vincristine sulfate: Given IV

pralatrexate: Given IV

laboratory biomarker analysis: Correlative studies

comparative genomic hybridization: Correlative studies

gene expression analysis: Correlative studies

nucleic acid sequencing: Correlative studies

mutation analysis: Correlative studies

Overall Number of Participants Analyzed 33
Measure Type: Number
Unit of Measure: percentage of participants analyzed
70
3.Secondary Outcome
Title Event Free Survival (EFS)
Hide Description Estimated 2-year Event Free Survival (EFS), as well as plots of EFS, will be produced using the method of Kaplan-Meier, along with 95% confidence intervals for EFS. Event-free survival is defined as time from therapy until relapse, progression, or death from any cause.
Time Frame 2 years
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Hide Analysis Population Description
All evaluable patients irrespective of the total number of cycles of therapy received were included in the EFS and OS analyses.
Arm/Group Title Treatment (Chemotherapy and Enzyme Inhibitor Therapy)
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Patients receive cyclophosphamide IV and vincristine sulfate IV on day 1, etoposide IV on days 1-3 or PO QD on days 2-3, and prednisone PO QD on days 1-5 (CEOP administration). Patients also receive pralatrexate IV over 3-5 minutes on days 15, 22, and 29 (P administration). Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients with CR or PR, per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation.

prednisone: Given PO

cyclophosphamide: Given IV

etoposide: Given PO or IV

vincristine sulfate: Given IV

pralatrexate: Given IV

laboratory biomarker analysis: Correlative studies

comparative genomic hybridization: Correlative studies

gene expression analysis: Correlative studies

nucleic acid sequencing: Correlative studies

mutation analysis: Correlative studies

Overall Number of Participants Analyzed 33
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants analyzed
39
(21 to 57)
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description Estimated 2-year Overall Survival (OS), as well as plots of OS, will be produced using the method of Kaplan-Meier, along with 95% confidence intervals for OS. Overall survival is defined as time from the first chemotherapy administered on trial until death from any cause.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
All evaluable patients irrespective of the total number of cycles of therapy received were included in EFS and OS analyses.
Arm/Group Title Treatment (Chemotherapy and Enzyme Inhibitor Therapy)
Hide Arm/Group Description:

Patients receive cyclophosphamide IV and vincristine sulfate IV on day 1, etoposide IV on days 1-3 or PO QD on days 2-3, and prednisone PO QD on days 1-5 (CEOP administration). Patients also receive pralatrexate IV over 3-5 minutes on days 15, 22, and 29 (P administration). Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients with CR or PR, per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation.

prednisone: Given PO

cyclophosphamide: Given IV

etoposide: Given PO or IV

vincristine sulfate: Given IV

pralatrexate: Given IV

laboratory biomarker analysis: Correlative studies

comparative genomic hybridization: Correlative studies

gene expression analysis: Correlative studies

nucleic acid sequencing: Correlative studies

mutation analysis: Correlative studies

Overall Number of Participants Analyzed 33
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants analyzed
60
(39 to 76)
5.Secondary Outcome
Title To Evaluate the Safety and Tolerability of the Regimen by the Percent of Participants With Indicated Adverse Events
Hide Description Adverse events will be summarized using patient level incidence rates so that a patient contributes once to any adverse event. The number and percentage of patients with any adverse event will be summarized for each course. Serious adverse events will be analyzed similarly.
Time Frame 22 months
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients who received at least one cycle of chemotherapy were evaluable for toxicity.
Arm/Group Title Treatment (Chemotherapy and Enzyme Inhibitor Therapy)
Hide Arm/Group Description:

Patients receive cyclophosphamide IV and vincristine sulfate IV on day 1, etoposide IV on days 1-3 or PO QD on days 2-3, and prednisone PO QD on days 1-5 (CEOP administration). Patients also receive pralatrexate IV over 3-5 minutes on days 15, 22, and 29 (P administration). Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients with CR or PR, per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation.

prednisone: Given PO

cyclophosphamide: Given IV

etoposide: Given PO or IV

vincristine sulfate: Given IV

pralatrexate: Given IV

laboratory biomarker analysis: Correlative studies

comparative genomic hybridization: Correlative studies

gene expression analysis: Correlative studies

nucleic acid sequencing: Correlative studies

mutation analysis: Correlative studies

Overall Number of Participants Analyzed 33
Measure Type: Number
Unit of Measure: percentage of participants
Grade 3-4 anaemia 27
Grade 3-4 thrombocoytopenia 12
Grade 3-4 febrile neutropenia 18
Grade 3-4 mucositis 18
Grade 3-4 sepsis 15
Grade 3-4 increased creatinine 12
Grade 3-4 liver transaminases 12
6.Secondary Outcome
Title Percent of Patients Who Proceeded With Transplant
Hide Description Percentage of patients who received consolidation with high dose therapy and autologous stem cell rescue (HDT/SCR).
Time Frame 168-252 days (4 courses up to 6 courses of treatment)
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Hide Analysis Population Description
Thirty-three patients were analyzed. One patient withdrew consent before starting therapy.
Arm/Group Title Treatment
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"A" Treatment: Cyclophosphamide,Etoposide, Vincristine and Prednisone (CEOP) "B" Treatment: Pralatrexate (P)

“A” cycles (CEOP) of the treatment regimen are 14 days, followed by “ B” cycles (P) which are 21 days, followed by 7 days of rest for a total of 42 days per course, unless criteria are met for stopping or holding treatment or to a maximum of 6 courses.

Patients with Complete Response (CR) or Partial Response (PR), per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation.

Overall Number of Participants Analyzed 33
Measure Type: Count of Participants
Unit of Measure: Participants
15
  45.5%
Time Frame 20 months
Adverse Event Reporting Description Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
 
Arm/Group Title Treatment (Chemotherapy and Enzyme Inhibitor Therapy)
Hide Arm/Group Description

Patients receive cyclophosphamide IV and vincristine sulfate IV on day 1, etoposide IV on days 1-3 or PO QD on days 2-3, and prednisone PO QD on days 1-5 (CEOP administration). Patients also receive pralatrexate IV over 3-5 minutes on days 15, 22, and 29 (P administration). Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients with CR or PR, per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation.

prednisone: Given PO

cyclophosphamide: Given IV

etoposide: Given PO or IV

vincristine sulfate: Given IV

pralatrexate: Given IV

laboratory biomarker analysis: Correlative studies

comparative genomic hybridization: Correlative studies

gene expression analysis: Correlative studies

nucleic acid sequencing: Correlative studies

mutation analysis: Correlative studies

All-Cause Mortality
Treatment (Chemotherapy and Enzyme Inhibitor Therapy)
Affected / at Risk (%)
Total   12/33 (36.36%)    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment (Chemotherapy and Enzyme Inhibitor Therapy)
Affected / at Risk (%) # Events
Total   13/33 (39.39%)    
Blood and lymphatic system disorders   
Febrile neutropenia  1  5/33 (15.15%)  5
Cardiac disorders   
Sinus tachycardia  1  1/33 (3.03%)  1
Thrombotic thrombocytopenic purpura  1  1/33 (3.03%)  1
Gastrointestinal disorders   
Mucositis oral  1  1/33 (3.03%)  1
General disorders   
Fever  1  4/33 (12.12%)  6
Hepatobiliary disorders   
Hepatic failure  1  1/33 (3.03%)  1
Infections and infestations   
Lung Infection  1  3/33 (9.09%)  4
Sepsis  1  5/33 (15.15%)  5
Infections and infestations - Other, specify  1 [1]  1/33 (3.03%)  1
Injury, poisoning and procedural complications   
Kidney anastomotic leak  1  1/33 (3.03%)  1
Investigations   
Blood bilirubin increased  1  1/33 (3.03%)  1
Neutrophil count decreased  1  3/33 (9.09%)  3
White blood cell decreased  1  1/33 (3.03%)  1
Platelet count decreased  1  1/33 (3.03%)  1
Aspartate aminotransferase increased  1  1/33 (3.03%)  1
Alanine aminotransferase increased  1  1/33 (3.03%)  1
Metabolism and nutrition disorders   
Hyponatremia  1  1/33 (3.03%)  1
Hyperkalemia  1  1/33 (3.03%)  1
Anorexia  1  1/33 (3.03%)  1
Hypermagnesemia  1  1/33 (3.03%)  1
Nervous system disorders   
Headache  1  1/33 (3.03%)  1
Encephalopathy  1  1/33 (3.03%)  1
Psychiatric disorders   
Agitation  1  1/33 (3.03%)  1
Renal and urinary disorders   
Renal and urinary disorders - Other, specify  1 [2]  1/33 (3.03%)  1
Reproductive system and breast disorders   
Hypoxia  1  2/33 (6.06%)  2
Respiratory, thoracic and mediastinal disorders   
Cough  1  1/33 (3.03%)  1
Bronchospasm  1  1/33 (3.03%)  1
Pleural effusion  1  1/33 (3.03%)  1
Atelectasis  1  1/33 (3.03%)  1
Pulmonary Edema  1  1/33 (3.03%)  1
Respiratory, thoracic and mediastinal disorders - Other, specify  1 [3]  1/33 (3.03%)  1
Respiratory Failure  1  2/33 (6.06%)  3
Dyspnea  1  1/33 (3.03%)  1
Stridor  1  1/33 (3.03%)  1
Vascular disorders   
Vascular disorders - Other, specify  1  1/33 (3.03%)  1
Hypotension  1  1/33 (3.03%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
[1]
cellulitis
[2]
Creatinine increased
[3]
Acute respiratory distress syndrome (ARDS)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment (Chemotherapy and Enzyme Inhibitor Therapy)
Affected / at Risk (%) # Events
Total   19/33 (57.58%)    
Blood and lymphatic system disorders   
Blood and lymphatic system disorders - Other, specify  1 [1]  2/33 (6.06%)  5
Anemia  1  7/33 (21.21%)  14
Gastrointestinal disorders   
Mucositis oral  1  3/33 (9.09%)  4
General disorders   
Fever  1  3/33 (9.09%)  3
Investigations   
Neutrophil count decreased  1  7/33 (21.21%)  9
Creatinine increased  1  3/33 (9.09%)  4
White blood cell decreased  1  3/33 (9.09%)  3
Metabolism and nutrition disorders   
hypocalcemia  1  3/33 (9.09%)  7
Hyponatremia  1  3/33 (9.09%)  3
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
[1]
decreased leukocytes
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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
Layout table for Results Point of Contact information
Name/Title: Julie M. Vose, M.D.
Organization: University of Nebraska Medical Center
Phone: 402-559-3848
EMail: jmvose@unmc.edu
Layout table for additonal information
Responsible Party: Julie M Vose, MD, University of Nebraska
ClinicalTrials.gov Identifier: NCT01336933     History of Changes
Other Study ID Numbers: 569-10
NCI-2011-00254 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA036727 ( U.S. NIH Grant/Contract )
First Submitted: March 23, 2011
First Posted: April 18, 2011
Results First Submitted: February 4, 2018
Results First Posted: June 25, 2018
Last Update Posted: June 25, 2018