'A multi-centre phase II trial of early treatment intensification with R-ICE (rituximab – ifosfamide, carboplatin, etoposide) chemotherapy followed by BEAM ( BCNU(BCNU is Carmustine), etoposide, ara-C (ara-C is Cytarabine), melphalan) high dose chemotherapy and autologous stem cell transplantation for patients with poor prognosis diffuse large B-cell lymphoma
- Conditions
- Patients with CD20+ diffuse large B cell lymphoma (DLBCL) with low intermediate, high intermediate, or high risk disease or low risk disease with bulky tumour (> 7.5 cm) who are considered fit and eligible for high dose chemotherapy (HDCT) with Z-BEAM ( Zevalin - BEAM ( BCNU(BCNU is Carmustine), etoposide, ara-C (ara-C is Cytarabine), melphalan) and autologous stem cell transplantation (ASCT).Cancer - Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
- Registration Number
- ACTRN12609001077257
- Lead Sponsor
- Australasian Leukaemia and Lymphoma Group (ALLG)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 162
Inclusion criteria
1.Age 18 - 70 years
2.Male and female patients
3.Diagnosis of CD20-positive diffuse large B-cell lymphoma on biopsy
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
5. Low-intermediate, high-intermediate, high risk, or low risk disease with bulk (>7.5 cm)
6. Previously untreated (except for corticosteroids if required)
Patients considered suitable for dose-intense chemotherapy with R-CHOP-14 with Pegfilgrastim support
Eligible and fit for high dose chemotherapy with Z-BEAM and autologous stem-cell transplantation
Signed informed consent form
A positive baseline fluorodeoxyglucose(FDG) positron emission tomography(PET)
Exclusion criteria
1.Life-expectancy < 3 months
2.Transformed NonHodgkin lymphoma (NHL) or types of NHL other than DLBCL
3.Primary Central Nervous System (CNS) or gastrointestinal Mucosa-Associated Lymphoid Tissue (MALT)lymphoma
4.CD20-negative NHL
5. Documented Human Immunodeficiency Viris (HIV)
6. Seropositivity for Hepatitis B [Either 1. HbsAg (surface antigen) positive or 2. HbcAb (core antibody) positive and HbsAb (surface antibody) titre of < 100 iu/ml] unless clearly due to vaccination
7.Patients with good prognosis low risk disease (IPI = 0, 1) plus absence of bulk (= 7.5 cm).
8.Hypersensitivity to components of Zevalin including ibritumomab tiuxetan, Yttrium chloride, other murine proteins, or to any exipients
9.Pregnant woman
10.Previously treated lymphoma
11.Any serious active disease or co-morbid medical condition (according to investigator’s decision)
12.Non-compensated cardiac failure
13.Chronic lung disease with hypoxaemia
14.Severe psychiatric disease
15.Poor renal function (creatinine > 150 micromol/L), poor hepatic function (total bilirubin level > 30 mmol/L, transaminases > 2.5 maximum normal level) unless abnormalities are related to the lymphoma
16.Poor bone marrow reserve as defined by neutrophils < 1.5 x 109/L or platelets < 100 x 109/L, unless related to bone marrow infiltration
17.Any history of cancer during the last 5 years, with the exception of non-melanoma skin tumours or stage 0 (in situ) cervical carcinoma
18.Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary objective and endpoint:<br>The primary objective is to demonstrate an absolute improvement of 25% in two-year progression-free survival (PFS) from 20% to 45% in those patients with advanced stage DLBCL who have been identified with a positive interim-treatment PET/CT scan and switched to early treatment intensification using R-ICE chemotherapy followed by HDCT/ASCT in comparison with historical outcomes.<br><br>The primary endpoint for this trial is progression-free survival (PFS).[progression-free survival (PFS). PFS is defined as the time from the interim PET/CT scan (after the 4th cycle of R-CHOP-14) to the first observation of disease progression or death from any cause.]
- Secondary Outcome Measures
Name Time Method Secondary objectives and endpoints:<br>Event-free survival (EFS). measured for all patients who have a positive interim PET/CT scan after the 4th cycle of treatment. Also using complete metabolic response(CMR), or non-CMR or partial metabolic response, using qualative and semi-qualitative analysis[2 years post completion of treatment regimen];Complete remission rates. disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy by a PET scan[2 years post completion of treatment regimen];Relapse rates. by a PET scan[2 years post completion of treatment regimen];Overall survival rates.[2 years post completion of treatment regimen]