Clinical Trials /

CHOP vs GEM-P in 1st Line Treatment of T-cell Lymphoma, Multicentre Phase II Study

NCT01719835

Description:

This is a randomised, open-label phase II study comparing GEM-P chemotherapy (experimental arm) with CHOP (control arm) in previously untreated T-cell lymphoma. Eligible patients will be randomised 1:1 between 4-weekly GEM-P or 3-weekly CHOP chemotherapy.

Related Conditions:
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-Cell Lymphoma
  • Peripheral T-Cell Lymphoma
  • Peripheral T-Cell Lymphoma, Not Otherwise Specified
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CHOP vs GEM-P in 1st Line Treatment of T-cell Lymphoma, Multicentre Phase II Study
  • Official Title: CHEMO-T: Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone (CHOP) Versus Gemcitabine, Cisplatin and Methyl Prednisolone (GEM-P) in the First Line Treatment Of T-cell Lymphoma,a Multicentre Randomised Phase II Study

Clinical Trial IDs

  • ORG STUDY ID: RMH CCR: 3549
  • SECONDARY ID: 2011-004146-18
  • NCT ID: NCT01719835

Conditions

  • Peripheral T-cell Lymphoma NOS
  • Anaplastic Large Cell Lymphoma, ALK-Negative
  • Angioimmunoblastic T-cell Lymphoma
  • Hepatosplenic Gamma/ Delta T-cell Lymphoma
  • Enteropathy-Associated T-Cell Lymphoma

Interventions

DrugSynonymsArms
CyclophosphamideChemotherapy CHOP
GemcitabineChemotherapy GEM-P
DoxorubicinChemotherapy CHOP
VincristineChemotherapy CHOP
PrednisoloneChemotherapy CHOP
methylprednisoloneChemotherapy GEM-P
CisplatinChemotherapy GEM-P

Purpose

This is a randomised, open-label phase II study comparing GEM-P chemotherapy (experimental arm) with CHOP (control arm) in previously untreated T-cell lymphoma. Eligible patients will be randomised 1:1 between 4-weekly GEM-P or 3-weekly CHOP chemotherapy.

Detailed Description

      Background:

      T-cell lymphoma is an aggressive rare subset of Non-Hodgkin lymphoma (NHL) comprising several
      different subtypes of disease within this group. No standard first-line treatment exists for
      T-cell lymphoma as published series are small, with heterogeneous populations and often
      retrospective.

      Protocol Synopsis, Study Period: 5 years

      Objectives:

      Primary:

      • To compare the complete response rate of GEM-P with CHOP chemotherapy in the first line
      treatment of patients with T-Cell Lymphoma.

      Secondary:

      To investigate, between both arms:

        -  Rate of metabolic complete response

        -  Toxicity of treatment

        -  Overall survival (OS)

        -  Progression Free Survival (PFS)

      Exploratory:

      • Investigate impact of International Prognostic Index (IPI) on the outcomes response rate,
      PFS and OS

      Study Design:

      A randomised multi-centre open-label phase II study

      Indication: Previously untreated T-Cell lymphoma No of Participants: 186 (93 patients in each
      arm)

      Main Eligibility Criteria:

        -  Histologically proven T-cell lymphoma of the following subtypes:

        -  Peripheral T-cell lymphoma NOS

        -  Systemic Anaplastic large cell lymphoma (ALCL) Anaplastic lymphoma kinase (ALK) negative
           cases only

        -  Angioimmunoblastic T-cell lymphoma

        -  Hepatosplenic gamma/ delta T-cell lymphoma

        -  Enteropathy-associated T-cell lymphoma

        -  Bulky Stage I, Stage II, III or IV

        -  No prior chemotherapy regimen

        -  Patients aged 18 years or over.

        -  WHO performance status 0,1 or 2

        -  Adequate organ function:

        -  No Central Nervous System(CNS) or leptomeningeal involvement with lymphoma

        -  No treatment for lymphoma within 4 weeks of commencing trial therapy

        -  No known HIV, active Hepatitis B or C infection

      Treatment:

      CHOP: cyclophosphamide, doxorubicin, vincristine, prednisolone every 21 days. GEM-P:
      gemcitabine, methylprednisolone, cisplatin every 28 days.

      Assessment Schedule:

        -  Patients will be reviewed at baseline and prior to each scheduled dose of treatment for
           toxicity

        -  Radiological tumour assessment will be done with CT scan after every 2 cycles in Arm A
           and after cycle 1, 3 and 4 in Arm B

        -  PET/CT scan will be performed at baseline and upon completion of treatment..

        -  Follow up after completion of treatment will be 3, 6, 9, 12, 18, 24 months then annually
           for 5 years in total. CT scan will be performed at 3 & 12 months.

        -  Following disease progression patients will be followed for survival every 3 months
           until death
    

Trial Arms

NameTypeDescriptionInterventions
Chemotherapy GEM-PExperimentalGemcitabine, Methylprednisolone, Cisplatin
  • Gemcitabine
  • methylprednisolone
  • Cisplatin
Chemotherapy CHOPActive ComparatorCyclophosphamide, Doxorubicin, Vincristine, Prednisolone
  • Cyclophosphamide
  • Doxorubicin
  • Vincristine
  • Prednisolone

Eligibility Criteria

        Inclusion Criteria:

        Previously untreated, histologically proven T-cell Lymphoma (any of the following):

          -  Peripheral T-cell lymphoma Not Otherwise Specified (PTCL NOS)

          -  Systemic Anaplastic large cell lymphoma (ALCL) ALK negative cases only

          -  Angioimmunoblastic T-cell lymphoma

          -  Hepatosplenic gamma/ delta T-cell lymphoma

          -  Enteropathy-associated T-cell lymphoma (EATL)

               -  Bulky stage I not being considered for reduced chemotherapy plus involved field
                  radiotherapy or stage II, III or IV.

               -  Patient is male or female, and ≥18 years of age on the day of signing informed
                  consent.

               -  WHO performance status 0, 1 or 2.

               -  Cross sectional imaging from a baseline contrast enhanced CT should show at least
                  one measurable disease site that is at least 2 cm in longest diameter and
                  measurable in two perpendicular dimensions with or without corresponding
                  Fluorodeoxyglucose(FDG) avid lesions.

               -  Adequate cardiac function; formal assessment of left ventricular ejection
                  fraction is only required if clinically indicated (a baseline echocardiogram
                  should be done for patients with either hypertension, age > 60 years or history
                  of cardiac disease)

               -  Adequate bone marrow function: absolute neutrophil count (ANC) ≥1.0x109/l; white
                  blood cell count ≥ 3x109/l; platelets ≥ 100x109/l; haemoglobin (Hb) ≥ 9g/dl (can
                  be post-transfusion), unless deemed disease related

               -  Adequate renal function: calculated creatinine clearance ≥50ml/minute.

               -  Adequate liver function: serum bilirubin ≤1.5x Upper limit of normal (ULN);
                  Alanine transaminase/Aspartate transaminase (ALT/AST) ≤2.5x ULN; ALP ≤3x ULN (in
                  the absence of liver metastases). If liver metastases are present, ALT, AST or
                  Alkaline phosphatase (ALP) ≤5x ULN are permitted. Isolated hyperbilirubinaemia
                  due to Gilbert's disease is acceptable

               -  Female patient of childbearing potential must have a negative serum or urine
                  β-human chorionic gonadotropin(hCG)pregnancy test at baseline.

               -  Written informed consent must be obtained prior to start of study treatments.
                  Scans and bone marrow biopsies performed within 4 weeks of commencement of
                  therapy will be acceptable provided they have been performed according to study
                  requirements.

               -  Patient agreeable to use contraception for the period of study treatment and up
                  to 12 months after the last dose of study drugs.

        Exclusion Criteria:

          -  Documented or symptomatic central nervous system involvement or leptomeningeal
             disease.

          -  Patients with no measurable disease on the contrast enhanced CT scan at baseline.

          -  Any other clinically significant disease or co-morbidity which may adversely affect
             the safe delivery of treatment within this trial.

          -  Any other malignancies diagnosed or treated within the last 5 years (other than
             curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the
             cervix).

          -  Treatment with another investigational agent within 30 days of commencing study
             treatment.

          -  Known positive tests for human immunodeficiency virus (HIV) infection, hepatitis C
             virus, acute or active hepatitis B infection.

          -  Patient is pregnant or breastfeeding, or expecting to conceive or father children
             within one year of finishing study treatment.

          -  Patients with poorly controlled diabetes mellitus

          -  Hypersensitivity or contraindication to any of the study drugs as stated in the
             Summaries of product characteristics(SmPCs)for each of the study drugs. Patients with
             previous cardiac infarct but satisfactory cardiac function may be allowed at the
             discretion of Chief Investigator.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:complete response rate (CR/CRu)
Time Frame:approximately 20 weeks after randomisation
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Toxicity
Time Frame:approximately 20 weeks after randomisation
Safety Issue:
Description:using Common Terminology Criteria for Adverse Events (CTCAE)v4.0
Measure:Overall Survival
Time Frame:1 and 2 years
Safety Issue:
Description:
Measure:Progression Free survival
Time Frame:1 and 2 years
Safety Issue:
Description:
Measure:Metabolic Complete Response Rate
Time Frame:approximately 20 weeks after randomisation
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Royal Marsden NHS Foundation Trust

Trial Keywords

  • T-Cell Lymphoma
  • Untreated

Last Updated

March 15, 2018