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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Royal Marsden NHS Foundation Trust
Sponsor:
Collaborator:
Cancer Research UK
Information provided by (Responsible Party):
Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01719835
First received: April 12, 2012
Last updated: October 30, 2012
Last verified: October 2012
  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.


Condition Intervention Phase
Peripheral T-cell Lymphoma NOS
Anaplastic Large Cell Lymphoma, ALK-Negative
Angioimmunoblastic T-cell Lymphoma
Hepatosplenic Gamma/ Delta T-cell Lymphoma
Drug: Cyclophosphamide
Drug: Gemcitabine
Drug: Doxorubicin
Drug: Vincristine
Drug: Prednisolone
Drug: methylprednisolone
Drug: Cisplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Royal Marsden NHS Foundation Trust:

Primary Outcome Measures:
  • complete response rate (CR/CRu) [ Time Frame: approximately 20 weeks after randomisation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity [ Time Frame: approximately 20 weeks after randomisation ] [ Designated as safety issue: Yes ]
    using Common Terminology Criteria for Adverse Events (CTCAE)v4.0

  • Overall Survival [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
  • Progression Free survival [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
  • Metabolic Complete Response Rate [ Time Frame: approximately 20 weeks after randomisation ] [ Designated as safety issue: No ]

Estimated Enrollment: 186
Study Start Date: March 2012
Estimated Study Completion Date: August 2022
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chemotherapy GEM-P
Gemcitabine, Methylprednisolone, Cisplatin
Drug: Gemcitabine
1000mg/m2 IV Days 1, 8, 15 every 28 days
Drug: methylprednisolone
1000mg oral or IV Days 1-5 every 28 days
Drug: Cisplatin
100mg/m2 IV Day 15 every 28 days
Active Comparator: Chemotherapy CHOP
Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone
Drug: Cyclophosphamide
750mg/m2 IV every 21 days
Drug: Doxorubicin
50mg/m2 IV every 21 days
Drug: Vincristine
1.4mg/m2 (max 2mg) IV every 21 days
Drug: Prednisolone
40mg/m2 oral Days 1-5 every 21 days

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
  • 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, Hepatitis C or active Hepatitis B viral 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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01719835

Contacts
Contact: David Cunningham, MD FRCP +44 (0) 208 661 3156 david.cunningham@rmh.nhs.uk

Locations
United Kingdom
Royal Marsden NHS Foundation Trust - London and Surrey Recruiting
London, United Kingdom, SM2 5PT
Contact: Ye mong To, BSc (Hons)    +44 (0) 208 661 3807    yemong.to@rmh.nhs.uk   
Principal Investigator: David Cunningham, MD FRCP         
Sponsors and Collaborators
Royal Marsden NHS Foundation Trust
Cancer Research UK
Investigators
Principal Investigator: David Cunningham, MD FRCP Royal Marsden NHS Foundation Trust
  More Information

No publications provided

Responsible Party: Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01719835     History of Changes
Other Study ID Numbers: RMH CCR: 3549, 2011-004146-18
Study First Received: April 12, 2012
Last Updated: October 30, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: National Institute for Health Research
United Kingdom: Research Ethics Committee

Keywords provided by Royal Marsden NHS Foundation Trust:
T cell lymphoma
untreated

Additional relevant MeSH terms:
Immunoblastic Lymphadenopathy
Lymphoma
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cisplatin
Cyclophosphamide
Doxorubicin
Gemcitabine
Liposomal doxorubicin
Methylprednisolone
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Vincristine
Alkylating Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antiemetics

ClinicalTrials.gov processed this record on October 23, 2014