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.
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
Drug | Synonyms | Arms |
---|
Cyclophosphamide | | Chemotherapy CHOP |
Gemcitabine | | Chemotherapy GEM-P |
Doxorubicin | | Chemotherapy CHOP |
Vincristine | | Chemotherapy CHOP |
Prednisolone | | Chemotherapy CHOP |
methylprednisolone | | Chemotherapy GEM-P |
Cisplatin | | Chemotherapy 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
Name | Type | Description | Interventions |
---|
Chemotherapy GEM-P | Experimental | Gemcitabine, Methylprednisolone, Cisplatin | - Gemcitabine
- methylprednisolone
- Cisplatin
|
Chemotherapy CHOP | Active Comparator | Cyclophosphamide, 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
Last Updated
March 15, 2018