Phase III study comparing R-CODOX-M/R-IVAC versus dose-adjusted EPOCH-R (DA-EPOCH-R) for patients with newly diagnosed high risk Burkitt lymphoma

Phase 1

Active, not recruiting

• Conditions: High risk Burkitt Lymphoma; MedDRA version: 20.0 Level: LLT Classification code 10006605 Term: Burkitt's tumor or lymphoma System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-004394-27-NL
• Lead Sponsor: HOVON Foundation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-03-26
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 260

Inclusion Criteria

• First diagnosis of high risk Burkitt lymphoma (sporadic and HIV associated), histologically confirmed according to the WHO classification 2008; Upon its availability the WHO 2016 classification should be used, to replace the WHO 2008 classification;
• High risk disease; i.e. any of following: elevated LDH, WHO performance status = 2 Ann Arbor stage III or IV , tumour mass >= 10 cm;
• Age 18-75 years inclusive;
• WHO performance status (PS) 0-3, WHO PS 4 only if disease related;
• 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 195
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 65

Exclusion Criteria

• All histopathological diagnoses other than Burkitt lymphoma according to the WHO classification 2008, irrespective of the presence of a MYC rearrangement;Upon its availability the WHO 2016 classification should be used, to replace the WHO 2008 classification;
• Patients with endemic Burkitt lymphoma;
• Patients with low risk Burkitt lymphoma (i.e. all of following: normal LDH, WHO performance status 0 or 1, Ann Arbor stage I or II, no tumour mass = 10 cm);
• Patients with CNS localization of Burkitt lymphoma;
• Prior treatment other than local radiation (max. 10 Gy) or short course (max 7 days) of steroids = 1 mg/kg or =100mg prednisolone (whichever is greater; or equivalent corticosteroid) or acute symptoms; or 1 cycle of R-CHOP
• Creatinine clearance < 50 ml/min unless lymphoma related;
• Inadequate hepatic function: bilirubin > 2.5 * ULN (total) except patients with Gilbert’s syndrome as defined by > 80% unconjugated;
• Inadequate haematological function ANC < 1x10^9/l and platelets < 75x10^9 /l unless lymphoma related;
• Severe pulmonary dysfunction (CTCAE grade 3-4);
• Severe neurological or psychiatric disease;
• Active symptomatic ischemic heart disease, myocardial infarction, or congestive heart failure within the past year. If an ultrasound or MUGA scan is obtained the LVEF should exceed 45%;
• All men and all women of child-bearing potential not willing or able to use an acceptable method of birth control for the duration of the study and one year beyond treatment completion;
• Female subject pregnant or breast-feeding;
• History of a prior invasive malignancy in the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma;
• Serious concomitant medical illnesses that would jeopardize the patient's ability to receive the regimen with reasonable safety, includig active hepatitis B (HBV) or hepatitis C (HCV) infection;
• Current participation in another clinical trial interfering with HO127;
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To confirm in a multicenter setting an improvement in PFS to 85% at 2 years of DA-EPOCH-R in patients with newly diagnosed high risk Burkitt lymphoma as compared to an expected PFS of 70% at 2 years for the control arm R-CODOX-M/R-IVAC;<br> Secondary Objective: - To evaluate Overall Response Rate (ORR) end-of- treatment, Event Free Survival (EFS) and Overall Survival (OS) at 2 years<br> - To evaluate both regimens with respect to CTCAE grade = 3 toxicity<br> - To evaluate both regimens with respect to hospitalization days<br> ;<br> Primary end point(s): - 2 years PFS; defined as time from registration to disease progression, relapse or death, whichever comes first. Patients still alive or lost to follow up are censored at the date they were last known to be alive<br> ;Timepoint(s) of evaluation of this end point: When data untill 2 years after registration of all patients are available

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): - ORR end-of-treatment<br> -EFS at 2 years; defined as time from registration to first event (death from any cause, no CR, relapse, whichever comes first).<br> -OS at 2 years; defined as time from registration until death from any cause; patients still alive or lost to follow up are censored at the date they were last known to be alive<br> - Rate of CTCAE grade =3 toxicities<br> - Number of hospitalization days<br> ;Timepoint(s) of evaluation of this end point: When data untill 2 years after registration of all patients are available