No registrations found.
ID
Source
Brief title
Health condition
Non-hodgkin lymphoma, Burkitt lymphoma
Burkitt lymfoom
Sponsors and support
P/a HOVON Data Center
Erasmus MC Cancer Institute, Clinical Trial Center
P.O. Box 2040
3000 CA Rotterdam
Tel: 010 4391568
Fax: 010 4391028
e-mail: hdc@erasmusmc.nl
- KWF
Intervention
Outcome measures
Primary outcome
2 year PFS; defined as time from
randomisation 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.
Secondary outcome
- ORR end-of-treatment
- EFS and OS at 2 years
- Rate of severe (CTCAE grade ≥3) toxicities
- Number of hospitalisation days
Background summary
Study phase: phase III
Study objectives:
Primary 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.
Secondary objectives:
- To evaluate Overall Response Rate (ORR) end-of-treatment, Event Free Survival (EFS)
and Overall Survival (OS) at 2 years
- To evaluate both regimens with respect to CTCAE grade ≥3 toxicity
- To evaluate both regimens with respect to hospitalisation
days
Patient population: Patients with newly diagnosed high risk Burkitt lymphoma 18 -75 years
Study design: prospective, multi-center, randomized
Duration of treatment: Arm A: 16 weeks, Arm B: 18 weeks
Study objective
The hypothesis to be tested is that the outcome in arm B is better than in arm A.
Study design
At entry, at mid treatment (after cycle 2 in arm A, after cycle 3 in arm B), at end of treatment, during follow-up (every 3 months until 6 months after completion of therapy, then every 6 months until 24 months after therapy, and then annually until 5 years after registration)
Intervention
Arm A: R-CODOX-M/R-IVAC
2 cycles of R-CODOX-M and 2 cycles R-IVAC
(alternately) total of 16 weeks (4 weeks per cycle)
R-CODOX-M consists of:
- rituximab i.v. (day 1,9: 375 mg/m^2/d)
- cyclophosphamide i.v. (day 1: 800 mg/m^2, day 2-5: 200 mg/m^2/d)
- vincristine i.v. (day 1,8: 1.5 mg/d)
- doxorubicin i.v. (day 1: 40 mg/m^2)
- methotrexate i.v.(day 10: 3000 mg/m^2 (<= 65 y), 1000 mg/m^2 (> 65 y))
R-IVAC consists of:
- rituximab i.v. (day 3,7: 375 mg/m^2/d)
- ifosfamide (day 1-5: 1500 mg/m^2/d (<=65 y), 1000 mg/m^2/d (>65 y))
- etoposide i.v. (day 1-5: 60 mg/m^2/d)
- cytarabine i.v. (day 1,2: 4000 mg/^2/d (<=65 y), 2000 mg/m^2/d (>65 y)
Both regimens also include supportive care and i.t. prophylaxis.
Arm B: DA-EPOCH-R
6 cycles, 3 weeks per cycle, total of 18 weeks
- etoposide i.v. (day 1-4: 50-124.4 mg/m^2/d continuous infusion, dose adjustment possible at every cycle)
- prednisolone p.o. (day 1-5 : 120 mg/m^2/d)
- vincristine i.v. (day 1-4: 0.4 mg/m^2/d continuous infusion)
- cyclophosphamide i.v. (day 5: 480-1866 mg/m^2/d dose adjustment possible at every cycle)
- doxorubicin i.v. (day 1-4 : 10-24.8 mg/m^2/d continuous infusion, dose adjustment possible at every cycle)
- rituximab i.v. (day 1,5: 375 mg/m^/d)
Also with supportive care and i.t. prophylaxis.
Dpt of Hematology<br>
De Boelelaan 1117
M.E.D. Chamuleau
Amsterdam 1081 HV
The Netherlands
+31 (0)20 4442604
m.chamuleau@vumc.nl
Dpt of Hematology<br>
De Boelelaan 1117
M.E.D. Chamuleau
Amsterdam 1081 HV
The Netherlands
+31 (0)20 4442604
m.chamuleau@vumc.nl
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.
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 localisation 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) for acute symptoms;
- 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
jeopardise the patient's ability to receive the
regimen with reasonable safety, including active hepatitis B
(HBV) or hepatitis C (HCV) infection;
- Current participation in another clinical trial if interfering
with HO127;
- Any psychological, familial, sociological and geographical
condition potentially hampering compliance with the study
protocol and follow-up schedule.
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL4429 |
| NTR-old | NTR4602 |
| Other | HOVON : HO127 |