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

• Sponsor: Mundipharma (China) Pharmaceutical Co. Ltd (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03349333
• Collaborator: (none)
• Enrollment: 85
• Location: 1
• Arm: 1
• Actual Duration (Months): 32.3
• Patients Per Site Per Month: 2.6

Study Details

Study Description

Brief Summary

This is a single arm, open-label, multi-center study designed to demonstrate the efficacy and safety of pralatrexate when administered concurrently with vitamin B12 and folic acid supplementation to patients with relapsed or refractory peripheral T-cell lymphoma(PTCL).

Condition or Disease	Intervention/Treatment	Phase
Refractory Peripheral T-Cell Lymphoma; Relapsed T-Cell Lymphoma	Drug: pralatrexate; Dietary Supplement: Vitamin B12 and folic acid	Phase 3

Detailed Description

The primary objective of this study is to confirm the objective response rate (ORR) among Chinese subjects with relapsed or refractory PTCL treated with pralatrexate together with concurrent vitamin B12 and folic acid supplementation

Primary endpoint is objective Response Rate by International Working Group Criteria

This study includes 3 phases: Screening, Treatment (pralatrexate) and Follow-up phases.

Screening Phase:

The screening phase will be up to 28 days duration (depending on availability of lab results).

Treatment (pralatrexate) Phase:

The start of study treatment (pralatrexate) is defined as the initiation of pralatrexate. Patients will attend the clinic weekly for 6 weeks of a 7-week cycle to receive pralatrexate, and will be examined by the treating physician. One cycle of pralatrexate therapy is 7 weeks in duration and consists of 6 weekly doses of pralatrexate administered via intravenous (IV) push over 3-5 minutes, followed by 1 week of rest.

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 (ie, prior to cycles 6, 8, etc.). Although radiological response assessments have been scheduled every 14 weeks, unscheduled radiological response assessments will be performed earlier if clinical progression is suspected.

Treatment with pralatrexate will continue until 24 months of administration, or until documented disease progression; unacceptable adverse event(s) indicating intolerance of the lowest study dose allowed (20 mg/m2/week); omission of 3 sequential doses of pralatrexate due to a treatment-related AE; 3-week lapse between pralatrexate doses; development of an AE, intercurrent illness, condition, or procedural complication that may interfere with the subject's participation; investigator's decision to withdraw the subject; subject withdraws consent; pregnancy of the subject; noncompliance with trial treatment or procedure requirements; or administrative reasons.

Follow-up phase:

All patients who received at least 1 dose of pralatrexate are to attend the Safety Follow-up Visit [30 (± 5) days after the last dose of pralatrexate] and the protocol defined procedures and evaluations will be performed.

After the Safety Follow-up Visit, Routine Follow-up Visits will be based on standard clinical care. All patients who received at least 1 dose of pralatrexate are to attend Routine Follow-up Visits, which will occur every 3 months (± 2 weeks) for determination of progression of disease, subsequent treatment initiation for T-cell lymphoma and survival after the Safety Follow-up Visit for a total duration of 24 months after the last dose of pralatrexate. The protocol-defined procedures/evaluations should be performed at each Routine Follow-up Visit.

Study Design

• Study Type: Interventional
• Actual Enrollment: 85 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Single Arm, Safety and Efficacy Study of Pralatrexate With Vitamin B12 and Folic Acid Supplementation in Subjects With Relapsed or Refractory Peripheral T-cell Lymphoma
• Actual Study Start Date: Sep 10, 2015
• Actual Primary Completion Date: Jul 21, 2017
• Actual Study Completion Date: May 21, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: pralatrexate Vitamin B12 and folic acid will be taken concurrently with pralatrexate

Drug: 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.; Dietary Supplement: 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.

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate(ORR) by International Working Group Criteria [2 years]

   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.

Secondary Outcome Measures

1. Time to Response (TTR) [2 years]

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

2. Progression-Free Survival (PFS) [2 years]

   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.

3. Overall Survival (OS) [4 years]

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

4. Duration of Responses [4 years]

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

5. Percentage of Participants With Treatment Emergent Adverse Events [4 years]

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

6. Area Under the Curve [AUC] for R-pralatrexate [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)]

   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.

7. Area Under the Curve [AUC] for S-pralatrexate [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）]

   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.

8. Steady State Volume of Distribution [Vdss] for R-pralatrexate [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)]

   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.

9. Steady State Volume of Distribution [Vdss] for S-pralatrexate [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）]

   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.

10. Steady State Clearance [CLss] for R-pralatrexate [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）]

    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.

11. Steady State Clearance [CLss] for S-pralatrexate [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）]

    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.

12. Maximum Observed Plasma Concentration [Cmax] for R-pralatrexate [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）]

    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.

13. Maximum Observed Plasma Concentration [Cmax] for S-pralatrexate [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）]

    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.

14. Time of Cmax Observation [Tmax] for R-pralatrexate [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）]

    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.

15. Time of Cmax Observation [Tmax] for S-pralatrexate [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）]

    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.

16. Terminal Phase Half-life [t1/2Z] for R-pralatrexate [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）]

    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.

17. Terminal Phase Half-life [t1/2Z] for S-pralatrexate [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）]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subject has histologically/cytologically confirmed PTCL, using the World Health

Organization (WHO) disease classification:

1. PTCL not otherwise specified (NOS)

2. Angioimmunoblastic T-cell lymphoma

3. Anaplastic large cell lymphoma, ALK+

4. Anaplastic large cell lymphoma, ALK-

5. Extranodal NK/T-cell lymphoma - nasal type

6. Enteropathy-associated T cell lymphoma

7. Hepatosplenic T-cell lymphoma

8. Subcutaneous panniculitis-like T-cell lymphoma

9. Adult T-cell lymphoma/leukemia (human T-cell leukemia virus [HTLV] 1+)

10. Aggressive NK-cell leukemia

11. Transformed mycosis fungoides

12. Subject has to have documented progressive disease (PD) after at least 1 prior systemic treatment.

13. Subject may not have received an experimental drug or biologic as their only prior therapy. Subject must have clear PD after the last treatment received. Subject should have at least 1 biopsy from initial diagnosis or in the relapsed setting to confirm the diagnosis of PTCL. Subject must have recovered from the toxic effects of prior therapy.

14. Subjects with an enlarged lymph node or extranodal mass lesion clearly measurable in two perpendicular directions and greater than 1.5 cm maximum diameter on computed tomography performed within 14 days prior to study enrollment.

15. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.

16. At least 18 years of age.

17. Expected life expectancy ≥ 3 months.

18. Adequate hematological, hepatic, and renal function as defined by:

• Absolute neutrophil count (ANC) ≥ 1000/uL (or 1109/L), platelet count ≥ 100,000/uL (or 100109/L) (at both screening and within 3 days prior to dosing on cycle 1, day 1)

• Total bilirubin ≤ 1.5 mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 X upper limit of normal (ULN) (AST/ALT < 5 X ULN if documented hepatic involvement with lymphoma)

• Creatinine ≤ 1.5 mg/dL (or 132.6 µmol/L) or a calculated creatinine clearance ≥ 50 mL/min

1. Women of childbearing potential must have agreed to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 30 days after the last administration of pralatrexate and must have a negative serum pregnancy test within 14 days prior to the first day of study treatment. Subjects who are postmenopausal for at least 1 year (> 12 months since last menses) or are surgically sterilized did not require this test.

2. Men who are not surgically sterile must agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 90 days after the last administration of pralatrexate.

3. Subject gives written informed consent (IC).

Exclusion Criteria:

1. Subject has:

2. Precursor T-cell lymphoma or leukemia

3. T-cell prolymphocytic leukemia (T-PLL)

4. T-cell large granular lymphocytic leukemia

5. Mycosis fungoides, other than transformed mycosis fungoides

6. Sézary syndrome

7. Primary cutaneous CD30+ T-cell disorders: Lymphoid papulosis and primary cutaneous anaplastic large cell lymphoma

8. Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix). If there is a history of prior malignancy, the patient must be disease-free for ≥ 5 years.

9. Congestive heart failure Class III/IV according to the New York Heart Association's Heart Failure guidelines.

10. Human immunodeficiency virus (HIV)-positive diagnosis.

11. Has, or history of, brain metastases or central nervous system (CNS) disease.

12. Active uncontrolled infection, underlying medical condition including unstable cardiac disease, or other serious illness that would impair the ability of the subject to receive protocol treatment.

13. Has major surgery within 2 weeks of study entry.

14. Receipt of any conventional chemotherapy or radiation therapy (RT) within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study treatment or planned use during the course of the study.

15. Receipt of corticosteroids within 7 days of study treatment, unless subject has been taking a continuous systemic dose of no more than 10 mg/day or equivalent dose of prednisone, or a local or inhaled or intranasal administration at fixed doses for at least 1 month prior to study treatment and tumor shrinkage was not observed.

16. Use of any investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the course of the study.

17. Receipt of anti-tumor antibody therapy within 100 days prior to study treatment.

18. History of allogeneic hematopoietic stem cell transplantation. Or subjects with a history of autologous hematopoietic stem cell transplantation within 100 days prior to study treatment.

19. Previous exposure to pralatrexate.

20. Subject is pregnant or breast-feeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Cancer Hospital	Beijing		China	100142

Sponsors and Collaborators

• Mundipharma (China) Pharmaceutical Co. Ltd

Investigators

• Study Director: Victoria YU, Mundipharma, China

Study Documents (Full-Text)

• Study Protocol - Apr 3, 2015
• Statistical Analysis Plan - Feb 7, 2018

More Information

Publications

None provided.

• Responsible Party: Mundipharma (China) Pharmaceutical Co. Ltd
• ClinicalTrials.gov Identifier: NCT03349333
• Other Study ID Numbers: FOT12-CN-301
• First Posted: Nov 21, 2017
• Last Update Posted: Oct 1, 2019
• Last Verified: Mar 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Mundipharma (China) Pharmaceutical Co. Ltd: FOT12-CN-301; PTCL (peripheral T-cell lymphoma); pralatrexate; vitamin B12; folic acid
• Additional relevant MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Folic Acid; Vitamin B 12; Hydroxocobalamin

Study Results

Participant Flow

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

Arm/Group Title	Pralatrexate
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

Baseline Characteristics

Arm/Group Title	PTCL Subtype
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 Participants	71
Age, Customized (years) [Mean (Standard Deviation) ]
Age(years)	54.5 (12.52)
Sex: Female, Male (Count of Participants)
Female	24 33.8%
Male	47 66.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	71 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
China	71 100%
Baseline Characteristics (Count of Participants)
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%
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%
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%
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%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate(ORR) by International Working Group Criteria
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

Outcome Measure Data

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
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.
Measure Participants	71
Count of Participants [Participants]	37 52.1%

2. Secondary Outcome

Title	Time to Response (TTR)
Description	Time to response was measured from first day of treatment to the first date of documented response.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pralatrexate
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.
Measure Participants	71
Mean (Standard Deviation) [months]	2.0947 (1.6590)

3. Secondary Outcome

Title	Progression-Free Survival (PFS)
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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pralatrexate
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.
Measure Participants	71
Median (95% Confidence Interval) [months]	4.76

4. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was measured from treatment day 1 until death or censoring.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pralatrexate
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.
Measure Participants	71
Median (95% Confidence Interval) [months]	18.00

5. Secondary Outcome

Title	Duration of Responses
Description	Duration of response was measured from first day of documented response to disease progression or death, whatever comes first.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pralatrexate
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.
Measure Participants	71
Median (95% Confidence Interval) [months]	8.67

6. Secondary Outcome

Title	Percentage of Participants With Treatment Emergent Adverse Events
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

Outcome Measure Data

Analysis Population Description

safety population

Arm/Group Title	Pralatrexate
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.
Measure Participants	71
Number [percentage of participants]	98.6 138.9%

7. Secondary Outcome

Title	Area Under the Curve [AUC] for R-pralatrexate
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)

Outcome Measure Data

Analysis Population Description

Based on PK population

Arm/Group Title	Pralatrexate
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.
Measure Participants	15
Pralatrexate-R in Cycle 1 week 6（20mg/m2）	2350.7402 (28.22)
Pralatrexate-R in Cycle 1 week 6（30mg/m2）	3979.1069 (152.16)
Pralatrexate-R in Cycle 1 day 1（30mg/m2）	3586.2925 (43.70)

8. Secondary Outcome

Title	Area Under the Curve [AUC] for S-pralatrexate
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）

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	Pralatrexate
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.
Measure Participants	15
Pralatrexate-S in Cycle 1 week 6（20mg/m2）	1364.7686 (22.65)
Pralatrexate-S in Cycle 1 week 6（30mg/m2）	2182.5078 (264.05)
Pralatrexate-S in Cycle 1 day 1（30mg/m2）	1674.8773 (38.32)

9. Secondary Outcome

Title	Steady State Volume of Distribution [Vdss] for R-pralatrexate
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)

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	Pralatrexate
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.
Measure Participants	15
Pralatrexate-R Cycle 1 day1（30mg/m2）	194.1589 (87.4028)
Pralatrexate-R Cycle 1 week6（20mg/m2）	344.2511 (109.8671)
Pralatrexate-R Cycle 1 week6（30mg/m2）	329.1892 (251.4938)

10. Secondary Outcome

Title	Steady State Volume of Distribution [Vdss] for S-pralatrexate
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）

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	Pralatrexate
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.
Measure Participants	15
Pralatrexate-S Cycle 1 Day 1 (30 mg/m2)	517.1628 (292.2888)
Pralatrexate-S Cycle 1 Week 6 (20 mg/m2)	1110.6541 (548.2687)
Pralatrexate-S Cycle 1 Week 6 (30 mg/m2)	1680.6116 (2292.0216)

11. Secondary Outcome

Title	Steady State Clearance [CLss] for R-pralatrexate
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）

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	Pralatrexate
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.
Measure Participants	15
Pralatrexate-R Cycle 1 Day 1 (30 mg/m2)	17.1914 (6.7903)
Pralatrexate-R Cycle 1 Week 6 (20 mg/m2)	16.3789 (5.3859)
Pralatrexate-R Cycle 1 Week 6 (30 mg/m2)	19.8406 (8.9265)

12. Secondary Outcome

Title	Steady State Clearance [CLss] for S-pralatrexate
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）

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	Pralatrexate
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.
Measure Participants	15
Pralatrexate-S Cycle 1 Day 1 (30 mg/m2)	34.6341 (17.9816)
Pralatrexate-S Cycle 1 Week 6 (20 mg/m2)	27.9794 (8.4317)
Pralatrexate-S Cycle 1 Week 6 (30 mg/m2)	45.2022 (22.4576)

13. Secondary Outcome

Title	Maximum Observed Plasma Concentration [Cmax] for R-pralatrexate
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）

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	Pralatrexate
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.
Measure Participants	15
Pralatrexate-R in Cycle 1 day 1（30mg/m2）	4649.6811 (83.74)
Pralatrexate-R in Cycle 1 week 6（20mg/m2）	2488.1502 (17.78)
Pralatrexate-R in Cycle 1 week 6（30mg/m2）	5064.6667 (421.48)

14. Secondary Outcome

Title	Maximum Observed Plasma Concentration [Cmax] for S-pralatrexate
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）

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	Pralatrexate
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.
Measure Participants	15
Pralatrexate-S in Cycle 1 day 1（30mg/m2）	3727.8582 (118.25)
Pralatrexate-S in Cycle 1 week 6（20mg/m2）	2325.5105 (24.22)
Pralatrexate-S in Cycle 1 week 6（30mg/m2）	3439.9695 (697.55)

15. Secondary Outcome

Title	Time of Cmax Observation [Tmax] for R-pralatrexate
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）

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	Pralatrexate
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.
Measure Participants	15
Pralatrexate-R in Cycle 1 day 1（30mg/m2）	0.1000
Pralatrexate-R in Cycle 1 week 6（20mg/m2）	0.1000
Pralatrexate-R in Cycle 1 week 6（30mg/m2）	0.1000

16. Secondary Outcome

Title	Time of Cmax Observation [Tmax] for S-pralatrexate
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）

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	Pralatrexate
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.
Measure Participants	15
Pralatrexate-S in Cycle 1 day 1（30mg/m2）	0.1000
Pralatrexate-S in Cycle 1 week 6（20mg/m2）	0.1000
Pralatrexate-S in Cycle 1 week 6（30mg/m2）	0.1000

17. Secondary Outcome

Title	Terminal Phase Half-life [t1/2Z] for R-pralatrexate
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）

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	Pralatrexate
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.
Measure Participants	15
Pralatrexate-R Cycle 1 Day 1 (30 mg/m2)	8.5040 (3.4927)
Pralatrexate-R Cycle 1 Week 6 (20 mg/m2)	14.6089 (0.1970)
Pralatrexate-R Cycle 1 Week 6 (30 mg/m2)	11.8249 (4.3282)

18. Secondary Outcome

Title	Terminal Phase Half-life [t1/2Z] for S-pralatrexate
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）

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	Pralatrexate
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.
Measure Participants	15
Pralatrexate-S Cycle 1 Day 1 (30 mg/m2)	10.8634 (5.6517)
Pralatrexate-S Cycle 1 Week 6 (20 mg/m2)	26.2505 (7.7381)
Pralatrexate-S Cycle 1 Week 6 (30 mg/m2)	24.8987 (23.2607)

Adverse Events

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.
Arm/Group Title	Pralatrexate
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 (%)	# Events
Total	29/71 (40.8%)
Serious Adverse Events
	Pralatrexate
	Affected / at Risk (%)	# Events
Total	35/71 (49.3%)
Blood and lymphatic system disorders
Thrombocytopenia	4/71 (5.6%)	4
Febrile neutropenia	3/71 (4.2%)	3
Pancytopenia	2/71 (2.8%)	2
Gastrointestinal disorders
Stomatitis	3/71 (4.2%)	3
Hepatobiliary disorders
Hepatic function abnormal	1/71 (1.4%)	1
Liver injury	1/71 (1.4%)	1
Infections and infestations
Lung infection	7/71 (9.9%)	8
Pneumonia	4/71 (5.6%)	5
Investigations
Platelet count decreased	10/71 (14.1%)	13
Other (Not Including Serious) Adverse Events
	Pralatrexate
	Affected / at Risk (%)	# Events
Total	70/71 (98.6%)
Blood and lymphatic system disorders
Neutropenia	22/71 (31%)	50
Gastrointestinal disorders
Stomatitis	48/71 (67.6%)	101

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.