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

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Brief Title

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

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

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).
    

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 Phase

Phase 3

Study Type

Interventional


Primary Outcome

Objective Response Rate(ORR) by International Working Group Criteria

Secondary Outcome

 Time to Response (TTR)

Condition

Refractory Peripheral T-Cell Lymphoma

Intervention

pralatrexate

Study Arms / Comparison Groups

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

85

Start Date

September 10, 2015

Completion Date

May 21, 2018

Primary Completion Date

July 21, 2017

Eligibility Criteria

        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:

          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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Victoria YU, , 

Location Countries

China

Location Countries

China

Administrative Informations


NCT ID

NCT03349333

Organization ID

FOT12-CN-301


Responsible Party

Sponsor

Study Sponsor

Mundipharma (China) Pharmaceutical Co. Ltd


Study Sponsor

Victoria YU, Study Director, Mundipharma, China


Verification Date

March 2019