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

NCT03349333 | Completed Phase 3 Results DMC

• 1 other identifier: FOT12-CN-301
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

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).

Conditions

Refractory Peripheral T-Cell Lymphoma; Relapsed T-Cell Lymphoma

Keywords

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

Outcome Measures

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.

  2 years

Secondary Outcomes (17)

• Time to Response (TTR)

  2 years

• Progression-Free Survival (PFS)

  2 years

• Overall Survival (OS)

  4 years

• Duration of Responses

  4 years

• Percentage of Participants With Treatment Emergent Adverse Events

  4 years

Study Arms (1)

pralatrexate

EXPERIMENTAL

Vitamin B12 and folic acid will be taken concurrently with pralatrexate

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

Interventions

pralatrexate DRUG

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.

pralatrexate

Vitamin B12 and folic acid DIETARY_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.

pralatrexate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Mundipharma (China) Pharmaceutical Co. Ltd: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, 100142, China

Location

Related Publications (1)

• 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.

  PMID: 30904980 DERIVED

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell

Interventions

10-propargyl-10-deazaaminopterin; Vitamin B 12; Folic Acid

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring

Results Point of Contact

• Title: clinical study manager
• Organization: Mundipharma(China) Co.,Ltd

guodong.lu@mundipharma.com.cn

8610-65636856

Study Officials

• Victoria YU

  Mundipharma, China

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2016
• First Posted: November 21, 2017
• Study Start: September 10, 2015
• Primary Completion: July 21, 2017
• Study Completion: May 21, 2018
• Last Updated: October 1, 2019
• Results First Posted: September 12, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)