Trial Outcomes & Findings for A Single Arm Study Evaluating the Efficacy and Safety of Pralatrexate in Subjects With Relapsed or Refractory PTCL (NCT NCT03349333)

Last Updated: 2019-10-01

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

85 participants

Primary outcome timeframe

2 years

Results posted on

2019-10-01

Participant Flow

In the protocol, 85 patients are planned to enroll. However, 71 patients are treated in the real situation.

Participant milestones

Participant milestones
Measure	Pralatrexate 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 Study STARTED	71
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	71

Reasons for withdrawal

Reasons for withdrawal
Measure	Pralatrexate 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 Study Progression of Disease	36
Overall Study Adverse Event	11
Overall Study Other	6
Overall Study Withdrawal by Subject	5
Overall Study Conditions interfere with participation	2
Overall Study Physician Decision	2
Overall Study 3-week lapse between pralatrexate doses	1
Overall Study Patients in treatment less than 24 month	8

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PTCL Subtype n=71 Participants 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.
Age, Customized Age(years)	54.5 years STANDARD_DEVIATION 12.52 • n=39 Participants
Sex: Female, Male Female	24 Participants n=39 Participants
Sex: Female, Male Male	47 Participants n=39 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=39 Participants
Race (NIH/OMB) Asian	71 Participants n=39 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=39 Participants
Race (NIH/OMB) Black or African American	0 Participants n=39 Participants
Race (NIH/OMB) White	0 Participants n=39 Participants
Race (NIH/OMB) More than one race	0 Participants n=39 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=39 Participants
Region of Enrollment China	71 Participants n=39 Participants
Baseline Characteristics Subtype of PTCL from investigator · PTCL not otherwise specified (NOS)	34 Participants n=39 Participants
Baseline Characteristics Subtype of PTCL from investigator · Angioimmunoblastic T-cell lymphoma	19 Participants n=39 Participants
Baseline Characteristics Subtype of PTCL from investigator · Anaplastic large cell lymphoma, ALK+	2 Participants n=39 Participants
Baseline Characteristics Subtype of PTCL from investigator · Anaplastic large cell lymphoma, ALK-	7 Participants n=39 Participants
Baseline Characteristics Subtype of PTCL from investigator · Extranodal NK/T-cell lymphoma - nasal type	5 Participants n=39 Participants
Baseline Characteristics Subtype of PTCL from investigator · Subcutaneous panniculitis-like T-cell lymphoma	2 Participants n=39 Participants
Baseline Characteristics Subtype of PTCL from investigator · Enteropathy-associated T cell lymphoma	1 Participants n=39 Participants
Baseline Characteristics Subtype of PTCL from investigator · Adult T-cell lymphoma/leukemia (human T-cell leuke	1 Participants n=39 Participants
Baseline Characteristics Subtype of PTCL from investigator · other	0 Participants n=39 Participants
Baseline Characteristics Subtype of PTCL from central review · PTCL not otherwise specified (NOS)	34 Participants n=39 Participants
Baseline Characteristics Subtype of PTCL from central review · Angioimmunoblastic T-cell lymphoma	20 Participants n=39 Participants
Baseline Characteristics Subtype of PTCL from central review · Anaplastic large cell lymphoma, ALK+	2 Participants n=39 Participants
Baseline Characteristics Subtype of PTCL from central review · Anaplastic large cell lymphoma, ALK-	6 Participants n=39 Participants
Baseline Characteristics Subtype of PTCL from central review · Extranodal NK/T-cell lymphoma - nasal type	5 Participants n=39 Participants
Baseline Characteristics Subtype of PTCL from central review · Subcutaneous panniculitis-like T-cell lymphoma	1 Participants n=39 Participants
Baseline Characteristics Subtype of PTCL from central review · Enteropathy-associated T cell lymphoma	1 Participants n=39 Participants
Baseline Characteristics Subtype of PTCL from central review · Adult T-cell lymphoma/leukemia (human T-cell leuke	1 Participants n=39 Participants
Baseline Characteristics Subtype of PTCL from central review · other	1 Participants n=39 Participants

PRIMARY outcome

Timeframe: 2 years

Population: The primary analysis was based on the independent review data using the safety population, safety population is 71 for this study

Outcome measures

Outcome measures
Measure	Pralatrexate n=71 Participants 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.
Objective Response Rate(ORR) by International Working Group Criteria	37 Participants

SECONDARY outcome

Timeframe: 2 years

Population: The secondary analyses was performed using the safety population and repeated using the per-protocol population.

Time to response was measured from first day of treatment to the first date of documented response.

Outcome measures

Outcome measures
Measure	Pralatrexate n=71 Participants 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.
Time to Response (TTR)	2.0947 months Standard Deviation 1.6590

SECONDARY outcome

Timeframe: 2 years

Population: The secondary analyses was performed using the safety population and repeated using the per-protocol population.

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.

Outcome measures

Outcome measures
Measure	Pralatrexate n=71 Participants 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.
Progression-Free Survival (PFS)	4.76 months Interval 3.06 to 8.75

SECONDARY outcome

Timeframe: 4 years

Population: The secondary analyses was performed using the safety population and repeated using the per-protocol population.

OS was measured from treatment day 1 until death or censoring.

Outcome measures

Outcome measures
Measure	Pralatrexate n=71 Participants 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 Survival (OS)	18.00 months Interval 10.35 to This analysis is based on cut off data, there are no enough events to estimated upper limit of 95% CI of median OS.

SECONDARY outcome

Timeframe: 4 years

Population: The secondary analyses was performed using the safety population and repeated using the per-protocol population.

Duration of response was measured from first day of documented response to disease progression or death, whatever comes first.

Outcome measures

Outcome measures
Measure	Pralatrexate n=71 Participants 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.
Duration of Responses	8.67 months Interval 3.32 to 14.13

SECONDARY outcome

Timeframe: 4 years

Population: safety population

treatment emergent AE was scheduled to be collected during all subject visits, the data evaluated as clinical significant will be summarized and presented.

Outcome measures

Outcome measures
Measure	Pralatrexate n=71 Participants 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.
Percentage of Participants With Treatment Emergent Adverse Events	98.6 percentage of participants

SECONDARY outcome

Timeframe: 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)

Population: Based on PK population

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.

Outcome measures

Outcome measures
Measure	Pralatrexate n=15 Participants 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.
Area Under the Curve [AUC] for R-pralatrexate Pralatrexate-R in Cycle 1 week 6（20mg/m2）	2350.7402 h*ng/ml Geometric Coefficient of Variation 28.22
Area Under the Curve [AUC] for R-pralatrexate Pralatrexate-R in Cycle 1 week 6（30mg/m2）	3979.1069 h*ng/ml Geometric Coefficient of Variation 152.16
Area Under the Curve [AUC] for R-pralatrexate Pralatrexate-R in Cycle 1 day 1（30mg/m2）	3586.2925 h*ng/ml Geometric Coefficient of Variation 43.70

SECONDARY outcome

Timeframe: 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）

Population: PK population

Outcome measures

Outcome measures
Measure	Pralatrexate n=15 Participants 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.
Area Under the Curve [AUC] for S-pralatrexate Pralatrexate-S in Cycle 1 week 6（20mg/m2）	1364.7686 h*ng/ml Geometric Coefficient of Variation 22.65
Area Under the Curve [AUC] for S-pralatrexate Pralatrexate-S in Cycle 1 week 6（30mg/m2）	2182.5078 h*ng/ml Geometric Coefficient of Variation 264.05
Area Under the Curve [AUC] for S-pralatrexate Pralatrexate-S in Cycle 1 day 1（30mg/m2）	1674.8773 h*ng/ml Geometric Coefficient of Variation 38.32

SECONDARY outcome

Timeframe: 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)

Population: PK population

Outcome measures

Outcome measures
Measure	Pralatrexate n=15 Participants 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.
Steady State Volume of Distribution [Vdss] for R-pralatrexate Pralatrexate-R Cycle 1 day1（30mg/m2）	194.1589 L Standard Deviation 87.4028
Steady State Volume of Distribution [Vdss] for R-pralatrexate Pralatrexate-R Cycle 1 week6（20mg/m2）	344.2511 L Standard Deviation 109.8671
Steady State Volume of Distribution [Vdss] for R-pralatrexate Pralatrexate-R Cycle 1 week6（30mg/m2）	329.1892 L Standard Deviation 251.4938

SECONDARY outcome

Timeframe: 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）

Population: PK population

Outcome measures

Outcome measures
Measure	Pralatrexate n=15 Participants 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.
Steady State Volume of Distribution [Vdss] for S-pralatrexate Pralatrexate-S Cycle 1 Day 1 (30 mg/m2)	517.1628 L Standard Deviation 292.2888
Steady State Volume of Distribution [Vdss] for S-pralatrexate Pralatrexate-S Cycle 1 Week 6 (20 mg/m2)	1110.6541 L Standard Deviation 548.2687
Steady State Volume of Distribution [Vdss] for S-pralatrexate Pralatrexate-S Cycle 1 Week 6 (30 mg/m2)	1680.6116 L Standard Deviation 2292.0216

SECONDARY outcome

Timeframe: 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）

Population: PK population

Outcome measures

Outcome measures
Measure	Pralatrexate n=15 Participants 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.
Steady State Clearance [CLss] for R-pralatrexate Pralatrexate-R Cycle 1 Day 1 (30 mg/m2)	17.1914 L/h Standard Deviation 6.7903
Steady State Clearance [CLss] for R-pralatrexate Pralatrexate-R Cycle 1 Week 6 (20 mg/m2)	16.3789 L/h Standard Deviation 5.3859
Steady State Clearance [CLss] for R-pralatrexate Pralatrexate-R Cycle 1 Week 6 (30 mg/m2)	19.8406 L/h Standard Deviation 8.9265

SECONDARY outcome

Timeframe: 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）

Population: PK population

Outcome measures

Outcome measures
Measure	Pralatrexate n=15 Participants 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.
Steady State Clearance [CLss] for S-pralatrexate Pralatrexate-S Cycle 1 Day 1 (30 mg/m2)	34.6341 L/h Standard Deviation 17.9816
Steady State Clearance [CLss] for S-pralatrexate Pralatrexate-S Cycle 1 Week 6 (20 mg/m2)	27.9794 L/h Standard Deviation 8.4317
Steady State Clearance [CLss] for S-pralatrexate Pralatrexate-S Cycle 1 Week 6 (30 mg/m2)	45.2022 L/h Standard Deviation 22.4576

SECONDARY outcome

Timeframe: 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）

Population: PK population

Outcome measures

Outcome measures
Measure	Pralatrexate n=15 Participants 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.
Maximum Observed Plasma Concentration [Cmax] for R-pralatrexate Pralatrexate-R in Cycle 1 day 1（30mg/m2）	4649.6811 ng/mL Geometric Coefficient of Variation 83.74
Maximum Observed Plasma Concentration [Cmax] for R-pralatrexate Pralatrexate-R in Cycle 1 week 6（20mg/m2）	2488.1502 ng/mL Geometric Coefficient of Variation 17.78
Maximum Observed Plasma Concentration [Cmax] for R-pralatrexate Pralatrexate-R in Cycle 1 week 6（30mg/m2）	5064.6667 ng/mL Geometric Coefficient of Variation 421.48

SECONDARY outcome

Timeframe: 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）

Population: PK population

Outcome measures

Outcome measures
Measure	Pralatrexate n=15 Participants 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.
Maximum Observed Plasma Concentration [Cmax] for S-pralatrexate Pralatrexate-S in Cycle 1 day 1（30mg/m2）	3727.8582 ng/mL Geometric Coefficient of Variation 118.25
Maximum Observed Plasma Concentration [Cmax] for S-pralatrexate Pralatrexate-S in Cycle 1 week 6（20mg/m2）	2325.5105 ng/mL Geometric Coefficient of Variation 24.22
Maximum Observed Plasma Concentration [Cmax] for S-pralatrexate Pralatrexate-S in Cycle 1 week 6（30mg/m2）	3439.9695 ng/mL Geometric Coefficient of Variation 697.55

SECONDARY outcome

Timeframe: 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）

Population: PK population

Outcome measures

Outcome measures
Measure	Pralatrexate n=15 Participants 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.
Time of Cmax Observation [Tmax] for R-pralatrexate Pralatrexate-R in Cycle 1 day 1（30mg/m2）	0.1000 h Interval 0.067 to 0.333
Time of Cmax Observation [Tmax] for R-pralatrexate Pralatrexate-R in Cycle 1 week 6（20mg/m2）	0.1000 h Interval 0.1 to 0.167
Time of Cmax Observation [Tmax] for R-pralatrexate Pralatrexate-R in Cycle 1 week 6（30mg/m2）	0.1000 h Interval 0.067 to 0.25

SECONDARY outcome

Timeframe: 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）

Population: PK population

Outcome measures

Outcome measures
Measure	Pralatrexate n=15 Participants 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.
Time of Cmax Observation [Tmax] for S-pralatrexate Pralatrexate-S in Cycle 1 day 1（30mg/m2）	0.1000 h Interval 0.067 to 0.333
Time of Cmax Observation [Tmax] for S-pralatrexate Pralatrexate-S in Cycle 1 week 6（20mg/m2）	0.1000 h Interval 0.1 to 0.167
Time of Cmax Observation [Tmax] for S-pralatrexate Pralatrexate-S in Cycle 1 week 6（30mg/m2）	0.1000 h Interval 0.067 to 0.25

SECONDARY outcome

Timeframe: 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）

Population: PK population

Outcome measures

Outcome measures
Measure	Pralatrexate n=15 Participants 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.
Terminal Phase Half-life [t1/2Z] for R-pralatrexate Pralatrexate-R Cycle 1 Day 1 (30 mg/m2)	8.5040 h Standard Deviation 3.4927
Terminal Phase Half-life [t1/2Z] for R-pralatrexate Pralatrexate-R Cycle 1 Week 6 (20 mg/m2)	14.6089 h Standard Deviation 0.1970
Terminal Phase Half-life [t1/2Z] for R-pralatrexate Pralatrexate-R Cycle 1 Week 6 (30 mg/m2)	11.8249 h Standard Deviation 4.3282

SECONDARY outcome

Timeframe: 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）

Population: PK population

Outcome measures

Outcome measures
Measure	Pralatrexate n=15 Participants 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.
Terminal Phase Half-life [t1/2Z] for S-pralatrexate Pralatrexate-S Cycle 1 Day 1 (30 mg/m2)	10.8634 h Standard Deviation 5.6517
Terminal Phase Half-life [t1/2Z] for S-pralatrexate Pralatrexate-S Cycle 1 Week 6 (20 mg/m2)	26.2505 h Standard Deviation 7.7381
Terminal Phase Half-life [t1/2Z] for S-pralatrexate Pralatrexate-S Cycle 1 Week 6 (30 mg/m2)	24.8987 h Standard Deviation 23.2607

Adverse Events

Pralatrexate

Serious events: 35 serious events

Other events: 70 other events

Deaths: 29 deaths

Serious adverse events

Serious adverse events
Measure	Pralatrexate n=71 participants at risk 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.
Infections and infestations Lung infection	9.9% 7/71 • Number of events 8 • 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.
Investigations Platelet count decreased	14.1% 10/71 • Number of events 13 • 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.
Blood and lymphatic system disorders Thrombocytopenia	5.6% 4/71 • Number of events 4 • 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.
Gastrointestinal disorders Stomatitis	4.2% 3/71 • Number of events 3 • 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.
Infections and infestations Pneumonia	5.6% 4/71 • Number of events 5 • 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.
Blood and lymphatic system disorders Febrile neutropenia	4.2% 3/71 • Number of events 3 • 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.
Blood and lymphatic system disorders Pancytopenia	2.8% 2/71 • Number of events 2 • 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.
Hepatobiliary disorders Hepatic function abnormal	1.4% 1/71 • Number of events 1 • 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.
Hepatobiliary disorders Liver injury	1.4% 1/71 • Number of events 1 • 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.

Other adverse events

Other adverse events
Measure	Pralatrexate n=71 participants at risk 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.
Gastrointestinal disorders Stomatitis	67.6% 48/71 • Number of events 101 • 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.
Blood and lymphatic system disorders Neutropenia	31.0% 22/71 • Number of events 50 • 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.

Additional Information

clinical study manager

Mundipharma(China) Co.,Ltd

Phone: 8610-65636856

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place