A Phase II Single Arm Study of the use of CODOX-M/IVAC with Rituximab (R-CODOX-M/IVAC) in the treatment of patients with Diffuse Large B-Cell Lymphoma (DLBCL) or Burkitt's Lymphoma (BL) of International Prognostic Index (IPI) High or High-Intermediate Risk - R-CODOX-M/IVAC
- Conditions
- Diffuse large B-cell lymphoma Burkitt's lymphomaMedDRA version: 13.1 Level: PT Classification code 10006595 Term: Burkitt's lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 13.1 Level: PT Classification code 10012818 Term: Diffuse large B-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2005-003479-19-GB
- Lead Sponsor
- niversity College London
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 150
a) Age 18-65 years (inclusive)
b) Histologically proven diffuse large B cell non-Hodgkin’s lymphoma (DLBCL) and all morphological variants or Burkitt’s lymphoma, according to the current World Health Organisation classification1. The B cell nature of the proliferation must be verified by the positivity with an anti-CD20 antibody. All histology will be reviewed by a central Lymphoma Trials Office pathology panel.
c) IPI score high-intermediate (score=3) or high (score=4, 5). IPI defined as stage III or IV, raised LDH, > 1 extranodal site and poor performance status – WHO performance status >/= 2.
d) Patients with a positive serology for HIV
'There is increasing evidence of equivalent outcomes in HIV negative and positive individuals so it is no longer appropriate to exclude all patients who are HIV positive from entry into this study. However there are also grounds for believing that some HIV positive patients with poor immunological function and / or poor performance status may be put at risk with this very intensive programme of chemo-immunotherapy. Therefore for patients known to be HIV positive only patients with one or none of the following criteria will be eligible
1. CD4 cell count less than 100/_L,
2. Prior history of opportunistic infections,
3. Karnofsky performance score less than 60 or Eastern Cooperative Oncology Group score (ECOG) > 2
e) Disease stage II - IV
f) No previous chemotherapy, radiotherapy or other investigational drug for this indication (although pre-treatment with steroids is acceptable)
g) Adequate bone marrow function with platelets > 100x109/l; neutrophils > 1.5x109/l at the time of study entry unless attributed to bone marrow infiltration by lymphoma.
h) Serum creatinine < 150 micromol/l, serum bilirubin < 35micromol/l and transaminases < 2.5 x upper limit of institutional normal range unless attributed to lymphoma.
i) Normal MUGA or echocardiogram without areas of abnormal contractility and normal left ventricular ejection fraction (LVEF). (Only applicable if over 60 years of age, past history of diabetes, cardiac disease, hypertension or abnormal resting ECG).
j) No concurrent uncontrolled medical condition.
k) No active malignant disease other than basal or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix in the last 10 years.
l) Life expectancy > 3 months.
m) Adequate contraceptive precautions for all patients of childbearing potential.
n) Written, informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
a) Disease stage I
b) T-cell lymphoma.
c) Previous history of treated or non-treated indolent lymphoma. However, diffuse large B cell patients not previously diagnosed who have some small cell infiltration in bone marrow or lymph node may be included.
d) Past history of heart failure or uncontrolled angina pectoris.
e) Cardiac contra-indication to doxorubicin (abnormal contractility on echocardiography or nuclear medicine examination [MUGA]).
f) Neurological contra-indication to vincristine (e.g. pre-existing diabetic neuropathy).
g) Any other serious active disease.
h) General status that does not allow the administration of 2 cycles of CODOX-M/IVAC according to the investigator.
i) Patients with a positive serology for HIV not satisfying the inclusion criteria in section 5.3.1, Hepatitis B or Hepatitis C
j) Medical or psychiatric conditions that compromise the patient’s ability to give informed consent.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> Secondary Objective: Secondary Outcome Measure:<br> <br> (1)Complete Response rate (CR and CRu)<br> <br> (2) Toxicity<br> ;Primary end point(s): Progression Free Survival;<br> Timepoint(s) of evaluation of this end point: - At months 4 and 12 post trial treatment<br> - At follow up visits post trial treatment<br> ;<br> Main Objective: Does the combination of Rituximab and CODOX-M/IVAC improve the progression free survival in patients with newly diagnosed diffuse large B cell lymphoma or Burkitt's lymphoma of international prognostic index high or high-intermediate risk?<br> <br> <br>
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): Complete Response / Complete response uncertain<br> Toxicity<br> ;<br> Timepoint(s) of evaluation of this end point: - Within 1 month of completing trial treatment<br> - At months 4 and 12 post trial treatment<br>