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CompletedNCT03349333Updated Oct 1, 2019Results posted

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

A Phase 3 interventional study of pralatrexate and Vitamin B12 and folic acid in Refractory Peripheral T-Cell Lymphoma and Relapsed T-Cell Lymphoma, sponsored by Mundipharma (China) Pharmaceutical Co. Ltd. Completed at 1 site in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-10-01.

Sponsored by Mundipharma (China) Pharmaceutical Co. Ltd · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
85
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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).

Read the 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.

02

Conditions studied

  • Refractory Peripheral T-Cell Lymphoma
  • Relapsed T-Cell Lymphoma

Keywords

  • FOT12-CN-301
  • PTCL (peripheral T-cell lymphoma)
  • pralatrexate
  • vitamin B12
  • folic acid
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
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
  2. Subject has to have documented progressive disease (PD) after at least 1 prior systemic treatment.
  3. 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.
  4. 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.
  5. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
  6. At least 18 years of age.
  7. Expected life expectancy ≥ 3 months.

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

    • Absolute neutrophil count (ANC) ≥ 1000/uL (or 1*109/L), platelet count ≥ 100,000/uL (or 100*109/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
  9. 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.
  10. 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.
  11. Subject gives written informed consent (IC).

Exclusion criteria

Exclusion Criteria:

  1. Subject has:

    1. Precursor T-cell lymphoma or leukemia
    2. T-cell prolymphocytic leukemia (T-PLL)
    3. T-cell large granular lymphocytic leukemia
    4. Mycosis fungoides, other than transformed mycosis fungoides
    5. Sézary syndrome
    6. Primary cutaneous CD30+ T-cell disorders: Lymphoid papulosis and primary cutaneous anaplastic large cell lymphoma
  2. 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.
  3. Congestive heart failure Class III/IV according to the New York Heart Association's Heart Failure guidelines.
  4. Human immunodeficiency virus (HIV)-positive diagnosis.
  5. Has, or history of, brain metastases or central nervous system (CNS) disease.
  6. 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.
  7. Has major surgery within 2 weeks of study entry.
  8. 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.
  9. 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.
  10. Use of any investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the course of the study.
  11. Receipt of anti-tumor antibody therapy within 100 days prior to study treatment.
  12. 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.
  13. Previous exposure to pralatrexate.
  14. Subject is pregnant or breast-feeding
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
85 participants (actual)

Study arms

  • Experimental
    pralatrexate

    Vitamin B12 and folic acid will be taken concurrently with pralatrexate

    Drug: pralatrexate · Dietary Supplement: Vitamin B12 and folic acid

Interventions

  • Drugpralatrexate

    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 supplementVitamin 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.

05

What researchers measure

Primary outcomes

  1. Objective Response Rate(ORR) by International Working Group Criteria

    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

Secondary outcomes

  1. Time to Response (TTR)

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

    Time frame: 2 years

  2. Progression-Free Survival (PFS)

    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

  3. Overall Survival (OS)

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

    Time frame: 4 years

  4. Duration of Responses

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

    Time frame: 4 years

  5. Percentage of Participants With Treatment Emergent Adverse Events

    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

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

    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)

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

    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）

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

    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)

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

    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）

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

    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）

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

    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）

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

    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）

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

    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）

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

    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）

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

    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）

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

    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）

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

    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）

06

Results

Posted Sep 12, 2019

Participant flow

Participant flow — Overall Study
MilestonePralatrexate
Started71
Completed0
Not completed71
Withdrew: Progression of disease36
Withdrew: Adverse event11
Withdrew: Other6
Withdrew: Withdrawal by subject5
Withdrew: Conditions interfere with participation2
Withdrew: Physician decision2
Withdrew: 3-week lapse between pralatrexate doses1
Withdrew: Patients in treatment less than 24 month8

Outcome measures

PrimaryObjective Response Rate(ORR) by International Working Group Criteria

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
Reported as:
Count of participants · Participants
Objective Response Rate(ORR) by International Working Group Criteria
ParticipantsPralatrexate
Objective Response Rate(ORR) by International Working Group Criteria37
SecondaryTime to Response (TTR)

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

Time frame:
2 years
Reported as:
Mean · months
Time to Response (TTR)
monthsPralatrexate
Time to Response (TTR)2.0947 ± 1.6590
SecondaryProgression-Free Survival (PFS)

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
Reported as:
Median · months
Progression-Free Survival (PFS)
monthsPralatrexate
Progression-Free Survival (PFS)4.76 (3.06 to 8.75)
SecondaryOverall Survival (OS)

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

Time frame:
4 years
Reported as:
Median · months
Overall Survival (OS)
monthsPralatrexate
Overall Survival (OS)18.00 (10.35 to NA)
SecondaryDuration of Responses

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

Time frame:
4 years
Reported as:
Median · months
Duration of Responses
monthsPralatrexate
Duration of Responses8.67 (3.32 to 14.13)
SecondaryPercentage of Participants With Treatment Emergent Adverse Events

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
Reported as:
Number · percentage of participants
Percentage of Participants With Treatment Emergent Adverse Events
percentage of participantsPralatrexate
Percentage of Participants With Treatment Emergent Adverse Events98.6
SecondaryArea Under the Curve [AUC] for R-pralatrexate

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)
Reported as:
Geometric mean · h*ng/ml
Area Under the Curve [AUC] for R-pralatrexate
h*ng/mlPralatrexate
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
SecondaryArea Under the Curve [AUC] for S-pralatrexate

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）
Reported as:
Geometric mean · h*ng/ml
Area Under the Curve [AUC] for S-pralatrexate
h*ng/mlPralatrexate
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
SecondarySteady State Volume of Distribution [Vdss] for R-pralatrexate

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)
Reported as:
Mean · L
Steady State Volume of Distribution [Vdss] for R-pralatrexate
LPralatrexate
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
SecondarySteady State Volume of Distribution [Vdss] for S-pralatrexate

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）
Reported as:
Mean · L
Steady State Volume of Distribution [Vdss] for S-pralatrexate
LPralatrexate
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
SecondarySteady State Clearance [CLss] for R-pralatrexate

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）
Reported as:
Mean · L/h
Steady State Clearance [CLss] for R-pralatrexate
L/hPralatrexate
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
SecondarySteady State Clearance [CLss] for S-pralatrexate

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）
Reported as:
Mean · L/h
Steady State Clearance [CLss] for S-pralatrexate
L/hPralatrexate
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
SecondaryMaximum Observed Plasma Concentration [Cmax] for R-pralatrexate

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）
Reported as:
Geometric mean · ng/mL
Maximum Observed Plasma Concentration [Cmax] for R-pralatrexate
ng/mLPralatrexate
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
SecondaryMaximum Observed Plasma Concentration [Cmax] for S-pralatrexate

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）
Reported as:
Geometric mean · ng/mL
Maximum Observed Plasma Concentration [Cmax] for S-pralatrexate
ng/mLPralatrexate
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
SecondaryTime of Cmax Observation [Tmax] for R-pralatrexate

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）
Reported as:
Median · h
Time of Cmax Observation [Tmax] for R-pralatrexate
hPralatrexate
Pralatrexate-R in Cycle 1 day 1（30mg/m2）0.1000 (0.067 to 0.333)
Pralatrexate-R in Cycle 1 week 6（20mg/m2）0.1000 (0.100 to 0.167)
Pralatrexate-R in Cycle 1 week 6（30mg/m2）0.1000 (0.067 to 0.250)
SecondaryTime of Cmax Observation [Tmax] for S-pralatrexate

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）
Reported as:
Median · h
Time of Cmax Observation [Tmax] for S-pralatrexate
hPralatrexate
Pralatrexate-S in Cycle 1 day 1（30mg/m2）0.1000 (0.067 to 0.333)
Pralatrexate-S in Cycle 1 week 6（20mg/m2）0.1000 (0.100 to 0.167)
Pralatrexate-S in Cycle 1 week 6（30mg/m2）0.1000 (0.067 to 0.250)
SecondaryTerminal Phase Half-life [t1/2Z] for R-pralatrexate

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）
Reported as:
Mean · h
Terminal Phase Half-life [t1/2Z] for R-pralatrexate
hPralatrexate
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
SecondaryTerminal Phase Half-life [t1/2Z] for S-pralatrexate

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）
Reported as:
Mean · h
Terminal Phase Half-life [t1/2Z] for S-pralatrexate
hPralatrexate
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

Collected over 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.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Pralatrexate29/71 (40.8%)35/71 (49.3%)70/71 (98.6%)
Most frequent serious events
Most frequent serious events
EventPralatrexate
Platelet count decreasedInvestigations10/71
Lung infectionInfections and infestations7/71
ThrombocytopeniaBlood and lymphatic system disorders4/71
PneumoniaInfections and infestations4/71
StomatitisGastrointestinal disorders3/71
Febrile neutropeniaBlood and lymphatic system disorders3/71
PancytopeniaBlood and lymphatic system disorders2/71
Hepatic function abnormalHepatobiliary disorders1/71
Liver injuryHepatobiliary disorders1/71
Most frequent other events
Most frequent other events
EventPralatrexate
StomatitisGastrointestinal disorders48/71
NeutropeniaBlood and lymphatic system disorders22/71

Baseline characteristics

Safety population is 71

Age, Customized
Age, Customized(years)PTCL Subtype
Age(years)54.5 ± 12.52
Sex: Female, Male
Sex: Female, Male(Participants)PTCL Subtype
Female24
Male47
Race (NIH/OMB)
Race (NIH/OMB)(Participants)PTCL Subtype
American Indian or Alaska Native0
Asian71
Native Hawaiian or Other Pacific Islander0
Black or African American0
White0
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(Participants)PTCL Subtype
China71
Baseline Characteristics
Baseline Characteristics(Participants)PTCL Subtype
Subtype of PTCL from investigator — PTCL not otherwise specified (NOS)34
Subtype of PTCL from investigator — Angioimmunoblastic T-cell lymphoma19
Subtype of PTCL from investigator — Anaplastic large cell lymphoma, ALK+2
Subtype of PTCL from investigator — Anaplastic large cell lymphoma, ALK-7
Subtype of PTCL from investigator — Extranodal NK/T-cell lymphoma - nasal type5
Subtype of PTCL from investigator — Subcutaneous panniculitis-like T-cell lymphoma2
Subtype of PTCL from investigator — Enteropathy-associated T cell lymphoma1
Subtype of PTCL from investigator — Adult T-cell lymphoma/leukemia (human T-cell leuke1
Subtype of PTCL from investigator — other0
Subtype of PTCL from central review — PTCL not otherwise specified (NOS)34
Subtype of PTCL from central review — Angioimmunoblastic T-cell lymphoma20
Subtype of PTCL from central review — Anaplastic large cell lymphoma, ALK+2
Subtype of PTCL from central review — Anaplastic large cell lymphoma, ALK-6
Subtype of PTCL from central review — Extranodal NK/T-cell lymphoma - nasal type5
Subtype of PTCL from central review — Subcutaneous panniculitis-like T-cell lymphoma1
Subtype of PTCL from central review — Enteropathy-associated T cell lymphoma1
Subtype of PTCL from central review — Adult T-cell lymphoma/leukemia (human T-cell leuke1
Subtype of PTCL from central review — other1
07

Study locations

1 site
  • Beijing Cancer Hospital
    Beijing, 100142, China
08

References and documents

Publications

  • Hong X, Song Y, Huang H, Bai B, Zhang H, Ke X, Shi Y, Zhu J, Lu G, Liebscher S, Cai C. Pralatrexate in Chinese Patients with Relapsed or Refractory Peripheral T-cell Lymphoma: A Single-arm, Multicenter Study. Target Oncol. 2019 Apr;14(2):149-158. doi: 10.1007/s11523-019-00630-y. PubMed 30904980 ↗

Study documents

  • Study protocol · Apr 3, 2015
  • Statistical analysis plan · Feb 7, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03349333
Lead sponsor
Mundipharma (China) Pharmaceutical Co. Ltd
Responsible party
Sponsor
First posted
Nov 21, 2017
Start date
Sep 10, 2015
Primary completion
Jul 21, 2017
Completion
May 21, 2018
Results posted
Sep 12, 2019
Last update
Oct 1, 2019

Study contacts

Victoria YU
study director · Mundipharma, China

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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