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Trial record 3 of 19 for:    pralatrexate AND PTCL

A Single Arm Study Evaluating the Efficacy and Safety of Pralatrexate in Subjects With Relapsed or Refractory PTCL

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ClinicalTrials.gov Identifier: NCT03349333
Recruitment Status : Completed
First Posted : November 21, 2017
Results First Posted : September 12, 2019
Last Update Posted : October 1, 2019
Sponsor:
Information provided by (Responsible Party):
Mundipharma (China) Pharmaceutical Co. Ltd

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Refractory Peripheral T-Cell Lymphoma
Relapsed T-Cell Lymphoma
Interventions Drug: pralatrexate
Dietary Supplement: Vitamin B12 and folic acid
Enrollment 85
Recruitment Details  
Pre-assignment Details In the protocol, 85 patients are planned to enroll. However, 71 patients are treated in the real situation.
Arm/Group Title Pralatrexate
Hide Arm/Group Description

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Period Title: Overall Study
Started 71
Completed 0
Not Completed 71
Reason Not Completed
Progression of Disease             36
Adverse Event             11
Other             6
Withdrawal by Subject             5
Conditions interfere with participation             2
Physician Decision             2
3-week lapse between pralatrexate doses             1
Patients in treatment less than 24 month             8
Arm/Group Title PTCL Subtype
Hide Arm/Group Description

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Baseline Participants 71
Hide Baseline Analysis Population Description
Safety population is 71
Age, Customized  
Mean (Standard Deviation)
Unit of measure:  Years
Age(years) Number Analyzed 71 participants
54.5  (12.52)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants
Female
24
  33.8%
Male
47
  66.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants
American Indian or Alaska Native
0
   0.0%
Asian
71
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
0
   0.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
China Number Analyzed 71 participants
71
Baseline Characteristics  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants
Subtype of PTCL from investigator PTCL not otherwise specified (NOS)
34
  47.9%
Angioimmunoblastic T-cell lymphoma
19
  26.8%
Anaplastic large cell lymphoma, ALK+
2
   2.8%
Anaplastic large cell lymphoma, ALK-
7
   9.9%
Extranodal NK/T-cell lymphoma - nasal type
5
   7.0%
Subcutaneous panniculitis-like T-cell lymphoma
2
   2.8%
Enteropathy-associated T cell lymphoma
1
   1.4%
Adult T-cell lymphoma/leukemia (human T-cell leuke
1
   1.4%
other
0
   0.0%
Subtype of PTCL from central review PTCL not otherwise specified (NOS)
34
  47.9%
Angioimmunoblastic T-cell lymphoma
20
  28.2%
Anaplastic large cell lymphoma, ALK+
2
   2.8%
Anaplastic large cell lymphoma, ALK-
6
   8.5%
Extranodal NK/T-cell lymphoma - nasal type
5
   7.0%
Subcutaneous panniculitis-like T-cell lymphoma
1
   1.4%
Enteropathy-associated T cell lymphoma
1
   1.4%
Adult T-cell lymphoma/leukemia (human T-cell leuke
1
   1.4%
other
1
   1.4%
1.Primary Outcome
Title Objective Response Rate(ORR) by International Working Group Criteria
Hide Description

ORR defined as the percentage of subjects with CR, CRu or PR as Best Overall Response.Evaluation of response must be performed within 7 days prior to the projected first dose of cycle 2-4 and then within 7 days prior to the projected first dose of every even-numbered subsequent cycle (i.e. prior to cycles 6, 8, etc). Unscheduled radiological response assessments will be performed earlier if clinical progression is suspected.The primary analysis will be conducted once all subjects have completed cycle 5 treatment or discontinued before. Study treatment may continue per investigator judgment for a maximum of 24 months.

Response will be assessed on the basis of clinical, radiological, and pathological criteria. Response will be assessed by independent central review and by the treating investigator. Central review assessors will be blinded to the response assessments by the treating investigator. The primary analysis will be based on response assessed by central review.

Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The primary analysis was based on the independent review data using the safety population, safety population is 71 for this study
Arm/Group Title Pralatrexate
Hide Arm/Group Description:

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Participants Analyzed 71
Measure Type: Count of Participants
Unit of Measure: Participants
37
  52.1%
2.Secondary Outcome
Title Time to Response (TTR)
Hide Description Time to response was measured from first day of treatment to the first date of documented response.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The secondary analyses was performed using the safety population and repeated using the per-protocol population.
Arm/Group Title Pralatrexate
Hide Arm/Group Description:

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Participants Analyzed 71
Mean (Standard Deviation)
Unit of Measure: months
2.0947  (1.6590)
3.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description PFS was measured from treatment day 1 until event or censoring. An event was defined as the earliest of the following: death from any cause or disease progression. Subjects undergoing transplant or any other subsequent therapy prior to documentation of PD was censored at that time. Progression of disease deems as 1. 50% increase from nadir in the SPD of any previously identified abnormal node for PRs or nonresponders, 2.Appearance of any new lesion during or at the end of therapy as per IWC criteria.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The secondary analyses was performed using the safety population and repeated using the per-protocol population.
Arm/Group Title Pralatrexate
Hide Arm/Group Description:

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Participants Analyzed 71
Median (95% Confidence Interval)
Unit of Measure: months
4.76
(3.06 to 8.75)
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was measured from treatment day 1 until death or censoring.
Time Frame 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
The secondary analyses was performed using the safety population and repeated using the per-protocol population.
Arm/Group Title Pralatrexate
Hide Arm/Group Description:

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Participants Analyzed 71
Median (95% Confidence Interval)
Unit of Measure: months
18.00 [1] 
(10.35 to NA)
[1]
This analysis is based on cut off data, there are no enough events to estimated upper limit of 95% CI of median OS.
5.Secondary Outcome
Title Duration of Responses
Hide Description Duration of response was measured from first day of documented response to disease progression or death, whatever comes first.
Time Frame 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
The secondary analyses was performed using the safety population and repeated using the per-protocol population.
Arm/Group Title Pralatrexate
Hide Arm/Group Description:

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Participants Analyzed 71
Median (95% Confidence Interval)
Unit of Measure: months
8.67
(3.32 to 14.13)
6.Secondary Outcome
Title Percentage of Participants With Treatment Emergent Adverse Events
Hide Description treatment emergent AE was scheduled to be collected during all subject visits, the data evaluated as clinical significant will be summarized and presented.
Time Frame 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
safety population
Arm/Group Title Pralatrexate
Hide Arm/Group Description:

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Participants Analyzed 71
Measure Type: Number
Unit of Measure: percentage of participants
98.6
7.Secondary Outcome
Title Area Under the Curve [AUC] for R-pralatrexate
Hide Description The PK endpoints was analysed using the PK population. The overall PK population is defined as all subjects who receive at least one dose of Investigational Medicinal Product (IMP) and have at least one primary PK parameter. Subjects with non-zero baseline concentrations of >5% of Cmax for either analyte (R-pralatrexate or S-pralatrexate) will be removed from the PK population.
Time Frame Cycle 1 day1,Cycle 1 week 6(Pre-injection, end-injection, 30 and 60 minutes, and 3, 5, 8, 12, 18, 24, 48, and 72 hours post-end injection)
Hide Outcome Measure Data
Hide Analysis Population Description
Based on PK population
Arm/Group Title Pralatrexate
Hide Arm/Group Description:

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Participants Analyzed 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/ml
Pralatrexate-R in Cycle 1 week 6(20mg/m2) Number Analyzed 3 participants
2350.7402
(28.22%)
Pralatrexate-R in Cycle 1 week 6(30mg/m2) Number Analyzed 8 participants
3979.1069
(152.16%)
Pralatrexate-R in Cycle 1 day 1(30mg/m2) Number Analyzed 14 participants
3586.2925
(43.70%)
8.Secondary Outcome
Title Area Under the Curve [AUC] for S-pralatrexate
Hide Description The PK endpoints was analysed using the PK population. The overall PK population is defined as all subjects who receive at least one dose of Investigational Medicinal Product (IMP) and have at least one primary PK parameter. Subjects with non-zero baseline concentrations of >5% of Cmax for either analyte (R-pralatrexate or S-pralatrexate) will be removed from the PK population.
Time Frame Cycle 1 day 1, Cycle 1 week 6(Pre-injection, end-injection, 30 and 60 minutes, and 3, 5, 8, 12, 18, 24, 48, and 72 hours post-end injection)
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Pralatrexate
Hide Arm/Group Description:

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Participants Analyzed 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/ml
Pralatrexate-S in Cycle 1 week 6(20mg/m2) Number Analyzed 3 participants
1364.7686
(22.65%)
Pralatrexate-S in Cycle 1 week 6(30mg/m2) Number Analyzed 7 participants
2182.5078
(264.05%)
Pralatrexate-S in Cycle 1 day 1(30mg/m2) Number Analyzed 7 participants
1674.8773
(38.32%)
9.Secondary Outcome
Title Steady State Volume of Distribution [Vdss] for R-pralatrexate
Hide Description The PK endpoints was analysed using the PK population. The overall PK population is defined as all subjects who receive at least one dose of Investigational Medicinal Product (IMP) and have at least one primary PK parameter. Subjects with non-zero baseline concentrations of >5% of Cmax for either analyte (R-pralatrexate or S-pralatrexate) will be removed from the PK population.
Time Frame Cycle 1 day 1, Cycle 1 week6(Pre-injection, end-injection, 30 and 60 minutes, and 3, 5, 8, 12, 18, 24, 48, and 72 hours post-end injection)
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Pralatrexate
Hide Arm/Group Description:

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: L
Pralatrexate-R Cycle 1 day1(30mg/m2) Number Analyzed 15 participants
194.1589  (87.4028)
Pralatrexate-R Cycle 1 week6(20mg/m2) Number Analyzed 3 participants
344.2511  (109.8671)
Pralatrexate-R Cycle 1 week6(30mg/m2) Number Analyzed 9 participants
329.1892  (251.4938)
10.Secondary Outcome
Title Steady State Volume of Distribution [Vdss] for S-pralatrexate
Hide Description The PK endpoints was analysed using the PK population. The overall PK population is defined as all subjects who receive at least one dose of Investigational Medicinal Product (IMP) and have at least one primary PK parameter. Subjects with non-zero baseline concentrations of >5% of Cmax for either analyte (R-pralatrexate or S-pralatrexate) will be removed from the PK population.
Time Frame Cycle 1 day 1, Cycle 1 week 6(Pre-injection, end-injection, 30 and 60 minutes, and 3, 5, 8, 12, 18, 24, 48, and 72 hours post-end injection)
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Pralatrexate
Hide Arm/Group Description:

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: L
Pralatrexate-S Cycle 1 Day 1 (30 mg/m2) Number Analyzed 15 participants
517.1628  (292.2888)
Pralatrexate-S Cycle 1 Week 6 (20 mg/m2) Number Analyzed 3 participants
1110.6541  (548.2687)
Pralatrexate-S Cycle 1 Week 6 (30 mg/m2) Number Analyzed 9 participants
1680.6116  (2292.0216)
11.Secondary Outcome
Title Steady State Clearance [CLss] for R-pralatrexate
Hide Description The PK endpoints was analysed using the PK population. The overall PK population is defined as all subjects who receive at least one dose of Investigational Medicinal Product (IMP) and have at least one primary PK parameter. Subjects with non-zero baseline concentrations of >5% of Cmax for either analyte (R-pralatrexate or S-pralatrexate) will be removed from the PK population.
Time Frame Cycle 1 day 1, Cycle 1 week 6(Pre-injection, end-injection, 30 and 60 minutes, and 3, 5, 8, 12, 18, 24, 48, and 72 hours post-end injection)
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Pralatrexate
Hide Arm/Group Description:

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: L/h
Pralatrexate-R Cycle 1 Day 1 (30 mg/m2) Number Analyzed 15 participants
17.1914  (6.7903)
Pralatrexate-R Cycle 1 Week 6 (20 mg/m2) Number Analyzed 3 participants
16.3789  (5.3859)
Pralatrexate-R Cycle 1 Week 6 (30 mg/m2) Number Analyzed 9 participants
19.8406  (8.9265)
12.Secondary Outcome
Title Steady State Clearance [CLss] for S-pralatrexate
Hide Description The PK endpoints was analysed using the PK population. The overall PK population is defined as all subjects who receive at least one dose of Investigational Medicinal Product (IMP) and have at least one primary PK parameter. Subjects with non-zero baseline concentrations of >5% of Cmax for either analyte (R-pralatrexate or S-pralatrexate) will be removed from the PK population.
Time Frame Cycle 1 day 1, Cycle 1 week 6(Pre-injection, end-injection, 30 and 60 minutes, and 3, 5, 8, 12, 18, 24, 48, and 72 hours post-end injection)
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Pralatrexate
Hide Arm/Group Description:

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: L/h
Pralatrexate-S Cycle 1 Day 1 (30 mg/m2) Number Analyzed 15 participants
34.6341  (17.9816)
Pralatrexate-S Cycle 1 Week 6 (20 mg/m2) Number Analyzed 3 participants
27.9794  (8.4317)
Pralatrexate-S Cycle 1 Week 6 (30 mg/m2) Number Analyzed 9 participants
45.2022  (22.4576)
13.Secondary Outcome
Title Maximum Observed Plasma Concentration [Cmax] for R-pralatrexate
Hide Description The PK endpoints was analysed using the PK population. The overall PK population is defined as all subjects who receive at least one dose of Investigational Medicinal Product (IMP) and have at least one primary PK parameter. Subjects with non-zero baseline concentrations of >5% of Cmax for either analyte (R-pralatrexate or S-pralatrexate) will be removed from the PK population.
Time Frame Cycle 1 day 1, Cycle 1 week 6(Pre-injection, end-injection, 30 and 60 minutes, and 3, 5, 8, 12, 18, 24, 48, and 72 hours post-end injection)
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Pralatrexate
Hide Arm/Group Description:

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Participants Analyzed 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Pralatrexate-R in Cycle 1 day 1(30mg/m2) Number Analyzed 15 participants
4649.6811
(83.74%)
Pralatrexate-R in Cycle 1 week 6(20mg/m2) Number Analyzed 3 participants
2488.1502
(17.78%)
Pralatrexate-R in Cycle 1 week 6(30mg/m2) Number Analyzed 9 participants
5064.6667
(421.48%)
14.Secondary Outcome
Title Maximum Observed Plasma Concentration [Cmax] for S-pralatrexate
Hide Description The PK endpoints was analysed using the PK population. The overall PK population is defined as all subjects who receive at least one dose of Investigational Medicinal Product (IMP) and have at least one primary PK parameter. Subjects with non-zero baseline concentrations of >5% of Cmax for either analyte (R-pralatrexate or S-pralatrexate) will be removed from the PK population.
Time Frame Cycle 1 day 1, Cycle 1 week 6(Pre-injection, end-injection, 30 and 60 minutes, and 3, 5, 8, 12, 18, 24, 48, and 72 hours post-end injection)
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Pralatrexate
Hide Arm/Group Description:

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Participants Analyzed 15
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Pralatrexate-S in Cycle 1 day 1(30mg/m2) Number Analyzed 15 participants
3727.8582
(118.25%)
Pralatrexate-S in Cycle 1 week 6(20mg/m2) Number Analyzed 3 participants
2325.5105
(24.22%)
Pralatrexate-S in Cycle 1 week 6(30mg/m2) Number Analyzed 9 participants
3439.9695
(697.55%)
15.Secondary Outcome
Title Time of Cmax Observation [Tmax] for R-pralatrexate
Hide Description The PK endpoints was analysed using the PK population. The overall PK population is defined as all subjects who receive at least one dose of Investigational Medicinal Product (IMP) and have at least one primary PK parameter. Subjects with non-zero baseline concentrations of >5% of Cmax for either analyte (R-pralatrexate or S-pralatrexate) will be removed from the PK population.
Time Frame Cycle 1 day 1, Cycle 1 week 6(Pre-injection, end-injection, 30 and 60 minutes, and 3, 5, 8, 12, 18, 24, 48, and 72 hours post-end injection)
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Pralatrexate
Hide Arm/Group Description:

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: h
Pralatrexate-R in Cycle 1 day 1(30mg/m2) Number Analyzed 15 participants
0.1000
(0.067 to 0.333)
Pralatrexate-R in Cycle 1 week 6(20mg/m2) Number Analyzed 3 participants
0.1000
(0.100 to 0.167)
Pralatrexate-R in Cycle 1 week 6(30mg/m2) Number Analyzed 9 participants
0.1000
(0.067 to 0.250)
16.Secondary Outcome
Title Time of Cmax Observation [Tmax] for S-pralatrexate
Hide Description The PK endpoints was analysed using the PK population. The overall PK population is defined as all subjects who receive at least one dose of Investigational Medicinal Product (IMP) and have at least one primary PK parameter. Subjects with non-zero baseline concentrations of >5% of Cmax for either analyte (R-pralatrexate or S-pralatrexate) will be removed from the PK population.
Time Frame Cycle 1 day 1, Cycle 1 week 6(Pre-injection, end-injection, 30 and 60 minutes, and 3, 5, 8, 12, 18, 24, 48, and 72 hours post-end injection)
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Pralatrexate
Hide Arm/Group Description:

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: h
Pralatrexate-S in Cycle 1 day 1(30mg/m2) Number Analyzed 15 participants
0.1000
(0.067 to 0.333)
Pralatrexate-S in Cycle 1 week 6(20mg/m2) Number Analyzed 3 participants
0.1000
(0.100 to 0.167)
Pralatrexate-S in Cycle 1 week 6(30mg/m2) Number Analyzed 9 participants
0.1000
(0.067 to 0.250)
17.Secondary Outcome
Title Terminal Phase Half-life [t1/2Z] for R-pralatrexate
Hide Description The PK endpoints was analysed using the PK population. The overall PK population is defined as all subjects who receive at least one dose of Investigational Medicinal Product (IMP) and have at least one primary PK parameter. Subjects with non-zero baseline concentrations of >5% of Cmax for either analyte (R-pralatrexate or S-pralatrexate) will be removed from the PK population.
Time Frame Cycle 1 day 1, Cycle 1 week 6(Pre-injection, end-injection, 30 and 60 minutes, and 3, 5, 8, 12, 18, 24, 48, and 72 hours post-end injection)
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Pralatrexate
Hide Arm/Group Description:

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: h
Pralatrexate-R Cycle 1 Day 1 (30 mg/m2) Number Analyzed 14 participants
8.5040  (3.4927)
Pralatrexate-R Cycle 1 Week 6 (20 mg/m2) Number Analyzed 3 participants
14.6089  (0.1970)
Pralatrexate-R Cycle 1 Week 6 (30 mg/m2) Number Analyzed 8 participants
11.8249  (4.3282)
18.Secondary Outcome
Title Terminal Phase Half-life [t1/2Z] for S-pralatrexate
Hide Description The PK endpoints was analysed using the PK population. The overall PK population is defined as all subjects who receive at least one dose of Investigational Medicinal Product (IMP) and have at least one primary PK parameter. Subjects with non-zero baseline concentrations of >5% of Cmax for either analyte (R-pralatrexate or S-pralatrexate) will be removed from the PK population.
Time Frame Cycle 1 day 1, Cycle 1 week 6(Pre-injection, end-injection, 30 and 60 minutes, and 3, 5, 8, 12, 18, 24, 48, and 72 hours post-end injection)
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Pralatrexate
Hide Arm/Group Description:

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: h
Pralatrexate-S Cycle 1 Day 1 (30 mg/m2) Number Analyzed 7 participants
10.8634  (5.6517)
Pralatrexate-S Cycle 1 Week 6 (20 mg/m2) Number Analyzed 3 participants
26.2505  (7.7381)
Pralatrexate-S Cycle 1 Week 6 (30 mg/m2) Number Analyzed 7 participants
24.8987  (23.2607)
Time Frame AEs were recorded in the eCRF from the point at which the ICF was signed until 30 (± 5) days after the last dose of pralatrexate. This included new AEs that were reported in the 30 (± 5) days after the last dose of pralatrexate.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Pralatrexate
Hide Arm/Group Description

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.

Vitamin B12 and folic acid: The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.

All-Cause Mortality
Pralatrexate
Affected / at Risk (%)
Total   29/71 (40.85%)    
Show Serious Adverse Events Hide Serious Adverse Events
Pralatrexate
Affected / at Risk (%) # Events
Total   35/71 (49.30%)    
Blood and lymphatic system disorders   
Thrombocytopenia *  4/71 (5.63%)  4
Febrile neutropenia *  3/71 (4.23%)  3
Pancytopenia *  2/71 (2.82%)  2
Gastrointestinal disorders   
Stomatitis *  3/71 (4.23%)  3
Hepatobiliary disorders   
Hepatic function abnormal *  1/71 (1.41%)  1
Liver injury *  1/71 (1.41%)  1
Infections and infestations   
Lung infection *  7/71 (9.86%)  8
Pneumonia *  4/71 (5.63%)  5
Investigations   
Platelet count decreased *  10/71 (14.08%)  13
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pralatrexate
Affected / at Risk (%) # Events
Total   70/71 (98.59%)    
Blood and lymphatic system disorders   
Neutropenia *  22/71 (30.99%)  50
Gastrointestinal disorders   
Stomatitis *  48/71 (67.61%)  101
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: clinical study manager
Organization: Mundipharma(China) Co.,Ltd
Phone: 8610-65636856
EMail: guodong.lu@mundipharma.com.cn
Layout table for additonal information
Responsible Party: Mundipharma (China) Pharmaceutical Co. Ltd
ClinicalTrials.gov Identifier: NCT03349333     History of Changes
Other Study ID Numbers: FOT12-CN-301
First Submitted: July 26, 2016
First Posted: November 21, 2017
Results First Submitted: June 28, 2018
Results First Posted: September 12, 2019
Last Update Posted: October 1, 2019