Refractory Peripheral T-Cell LymphomaPhase 3NCT03349333
A Single Arm Study Evaluating the Efficacy and Safety of Pralatrexate in Subjects With Relapsed or Refractory PTCL
A Phase 3 study testing pralatrexate and Vitamin B12 and folic acid in people with Refractory Peripheral T-Cell Lymphoma and Relapsed T-Cell Lymphoma, run by Mundipharma (China) Pharmaceutical Co. Ltd at 1 site in China.
Trial 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 more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Peripheral T-Cell Lymphoma, Relapsed T-Cell Lymphoma
- What is being tested?
- pralatrexate and Vitamin B12 and folic acid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 1 siteChina
- Study dates
- 10 Sep 2015to 21 May 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject has histologically/cytologically confirmed PTCL, using the World Health Organization (WHO) disease classification:
- PTCL not otherwise specified (NOS)
- Angioimmunoblastic T-cell lymphoma
- Anaplastic large cell lymphoma, ALK+
- Anaplastic large cell lymphoma, ALK-
- Extranodal NK/T-cell lymphoma - nasal type
Show all 25Show fewer
- Enteropathy-associated T cell lymphoma
- Hepatosplenic T-cell lymphoma
- Subcutaneous panniculitis-like T-cell lymphoma
- Adult T-cell lymphoma/leukemia (human T-cell leukemia virus [HTLV] 1+)
- Aggressive NK-cell leukemia
- Transformed mycosis fungoides
- Subject has to have documented progressive disease (PD) after at least 1 prior systemic treatment.
- 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.
- 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.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
- At least 18 years of age.
- Expected life expectancy ≥ 3 months.
- 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
- 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.
- 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.
- Subject gives written informed consent (IC).
Who cannot join
- Subject has:
- Precursor T-cell lymphoma or leukemia
- T-cell prolymphocytic leukemia (T-PLL)
- T-cell large granular lymphocytic leukemia
- Mycosis fungoides, other than transformed mycosis fungoides
- Sézary syndrome
Show all 20Show fewer
- Primary cutaneous CD30+ T-cell disorders: Lymphoid papulosis and primary cutaneous anaplastic large cell lymphoma
- 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.
- Congestive heart failure Class III/IV according to the New York Heart Association's Heart Failure guidelines.
- Human immunodeficiency virus (HIV)-positive diagnosis.
- Has, or history of, brain metastases or central nervous system (CNS) disease.
- 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.
- Has major surgery within 2 weeks of study entry.
- 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.
- 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.
- Use of any investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the course of the study.
- Receipt of anti-tumor antibody therapy within 100 days prior to study treatment.
- 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.
- Previous exposure to pralatrexate.
- Subject is pregnant or breast-feeding
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Being tested
- pralatrexate, Vitamin B12 and folic acid
- Keywords
- FOT12-CN-301, PTCL (peripheral T-cell lymphoma), pralatrexate, vitamin B12, folic acid
- Medical subject headings
- Lymphoma, T-Cell, Peripheral, Lymphoma, T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pralatrexateDrug
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 acidDietary supplement
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.
| Study group | Role | What they receive |
|---|---|---|
| pralatrexate | Experimental | Vitamin B12 and folic acid will be taken concurrently with pralatrexate Receives: Drug: pralatrexate; Dietary Supplement: Vitamin B12 and folic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Secondary outcomes (17)
Time to Response (TTR)
Time to response was measured from first day of treatment to the first date of documented response.
Measured: 2 years
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.
Measured: 2 years
Overall Survival (OS)
OS was measured from treatment day 1 until death or censoring.
Measured: 4 years
Duration of Responses
Duration of response was measured from first day of documented response to disease progression or death, whatever comes first.
Measured: 4 years
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.
Measured: 4 years
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.
Measured: 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)
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.
Measured: 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）
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.
Measured: 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)
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.
Measured: 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）
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.
Measured: 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）
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.
Measured: 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）
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.
Measured: 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）
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.
Measured: 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）
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.
Measured: 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）
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.
Measured: 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）
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.
Measured: 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）
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.
Measured: 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）
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2017
- Study start10 Sep 2015
- Primary completion21 Jul 2017
- Study completion21 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Refractory Peripheral T-Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mundipharma (China) Pharmaceutical Co. Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Victoria YU, Study director, Mundipharma, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03349333
- Sponsor's protocol ID
- FOT12-CN-301
- Status last verified
- Mar 2019
- First submitted
- 26 Jul 2016
- Last updated
- 1 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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 at a glance
From the registry record, last updated by the sponsor on 1 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03349333
- Acronym / sponsor ID
- FOT12-CN-301
- Keywords
- FOT12-CN-301, PTCL (peripheral T-cell lymphoma), pralatrexate, vitamin B12, folic acid
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Mundipharma (China) Pharmaceutical Co. LtdIndustry (pharma, biotech, devices)
- Study start
- 10 Sep 2015 (actual)
- Primary completion
- 21 Jul 2017 (actual)
- Study completion
- 21 May 2018 (actual)
- First posted
- 21 Nov 2017 (actual)
- Results
- Posted 12 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| pralatrexate | Experimental | Drug: pralatrexate, Dietary Supplement: Vitamin B12 and folic acidVitamin B12 and folic acid will be taken concurrently with pralatrexate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Subject has histologically/cytologically confirmed PTCL, using the World Health Organization (WHO) disease classification:
- Subject has to have documented progressive disease (PD) after at least 1 prior systemic treatment.
- 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.
- 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.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
Key exclusion criteria (20 listed)
- Subject has:
- 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.
- Congestive heart failure Class III/IV according to the New York Heart Association's Heart Failure guidelines.
- Human immunodeficiency virus (HIV)-positive diagnosis.
- Has, or history of, brain metastases or central nervous system (CNS) disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pralatrexatePralatrexate 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. | Drug | pralatrexate |
| Vitamin B12 and folic acidThe 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. | Dietary supplement | pralatrexate |
Primary outcome
Objective Response Rate(ORR) by International Working Group Criteria
Time frame: 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.
17 secondary outcomes
Time to Response (TTR)
Time frame: 2 years
Progression-Free Survival (PFS)
Time frame: 2 years
Overall Survival (OS)
Time frame: 4 years
Duration of Responses
Time frame: 4 years
Percentage of Participants With Treatment Emergent Adverse Events
Time frame: 4 years
Area Under the Curve [AUC] for R-pralatrexate
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)
Area Under the Curve [AUC] for S-pralatrexate
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）
Steady State Volume of Distribution [Vdss] for R-pralatrexate
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)
Steady State Volume of Distribution [Vdss] for S-pralatrexate
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）
Steady State Clearance [CLss] for R-pralatrexate
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）
Steady State Clearance [CLss] for S-pralatrexate
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）
Maximum Observed Plasma Concentration [Cmax] for R-pralatrexate
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）
Maximum Observed Plasma Concentration [Cmax] for S-pralatrexate
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）
Time of Cmax Observation [Tmax] for R-pralatrexate
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）
Time of Cmax Observation [Tmax] for S-pralatrexate
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）
Terminal Phase Half-life [t1/2Z] for R-pralatrexate
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）
Terminal Phase Half-life [t1/2Z] for S-pralatrexate
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）
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30904980Hong 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Victoria YU study director
Mundipharma, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing pralatrexate and Vitamin B12 and folic acid in people with Refractory Peripheral T-Cell Lymphoma and Relapsed T-Cell Lymphoma, run by Mundipharma (China) Pharmaceutical Co. Ltd at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate(ORR) by International Working Group Criteria (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03349333, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2019.