|- candidate number||14096|
|- NTR Number||NTR3750|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||14-dec-2012|
|- Secondary IDs||2012-003141-16 EudraCT|
|- Public Title||A trial to investigate the efficacy and feasibility of treatment with dose adjusted EPOCH-R (DA-EPOCH-R), adapted to risk profile in patients with newly diagnosed Burkitt lymphoma.|
|- Scientific Title||Efficacy and feasibility of first-line treatment with risk-adapted dose-adjusted EPOCH-R (DA-EPOCH-R) in patients with Burkitt lymphoma. A phase II clinical trial. |
|- ACRONYM||DA-EPOCH-R trial|
|- hypothesis||The DA-EPOCH-R regimen represents a major paradigm shift for the treatment of BL. Whereas standard treatment relies on dose density and intensity based on methotrexate and cytarabin to achieve adequate cell kill, DA-EPOCH-R relies on a pharmacodynamic based infusional schedule to improve the therapeutic index of chemotherapy. Based on the pilot results presented by Dunleavy at ICML 2011, DA-EPOCH- R appears to provide a high rate of cure with significantly lower treatment toxicity and tumor lysis syndrome compared to standard treatment. As such, DA-EPOCH-R may provide a major treatment advance in BL by lowering morbidity, mortality, and cost, while maintaining or possibly improving efficacy. The current protocol is aims to confirm the results obtained with DA-EPOCH-R in BL in Dutch general hematology practice, as this protocol has been conducted primarily by the NIH.|
|- Healt Condition(s) or Problem(s) studied||Burkitt lymphoma|
|- Inclusion criteria||1. First diagnosis of Burkitt lymphoma, histological confirmed according to the WHO classification 2008;|
2. Age ≥ 18 years;
3. No prior treatment except local radiation or short course steroids ≤ 1 mg/kg for acute symptoms;
4. All disease stages;
5. HIV negative or positive;
6. ECOG-WHO status 0-3, status 4 only if disease related;
7. Written informed consent.
|- Exclusion criteria||1. All histopathological diagnoses other than BL according to the WHO classification 2008, irrespective of the presence of MYC rearrangement;|
2. Inadequate renal function or creatinine clearance < 50 ml/min unless lymphoma related;
3. Inadequate hepatic function: bilirubin > 2 * ULN (total) except patients with Gilbert’s syndrome as defined by > 80% unconjugated;
4. Inadequate hematological function ANC < 1x109/l and platelets < 75x109 /l unless lymphoma related;
5. leukemic Burkitt lymphoma, defined as >30% blasts in bone-marrow and/or peripheral blood, without significant lympadenopathy;
6. Female subject of child-bearing potential not willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and one year beyond treatment completion;
7. Female subject pregnant or breast-feeding;
8. Male subject unwilling to use an acceptable method for contraception for the duration of the study and one year beyond treatment completion;
9. History of a prior invasive malignancy in past 5 years;
10. Active symptomatic ischemic heart disease, myocardial infarction, or congestive heart failure within the past year. If echo is obtained the LVEF should exceed 40%;
11. Serious concomitant medical illnesses that would jeopardize the patient's ability to receive the regimen with reasonable safety;
12. HIV positive patients not willing to suspend HAART therapy during the treatment period of the protocol.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, non-randomized|
|- planned startdate ||1-nov-2012|
|- planned closingdate||1-nov-2017|
|- Target number of participants||22|
|- Interventions||1. Low risk patients (3 cycles of Dose Adjusted EPOCH with 2xRituximab);|
2. High risk patients (6 cycles of DA-EPOCH-Rituximab).
EPOCH is Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin.
Low risk patients with a positive PET-CTscan after 2 cycles of DA-EPOCH-RR will receive 4 cycles of DA-EPOCH-R.
|- Primary outcome||1. 2 years overall survival (OS; time from registration. Patients still alive or lost to follow up are censored at the date they were last known to be alive) and progression free survival (PFS; i.e. time from registration to progression or death from any cause, whichever comes first);|
2. Number of cycles of the DA-EPOCH-R scheme completed on an out-patient –clinic basis.
|- Secondary outcome||Negative predictive value of low dose PET/CT scan after 2 cycles of DA-EPOCH-R on OS and PFS.|
|- Timepoints||Total expected study duration is 5 years.|
Study start (FPFV): Nov 2012;
Recruitment end (LPFV): Nov 2015;
Study end (LPLV): Nov 2017;
Completion of Clinical Study Report (CSR): June 2018;
Publication date: June 2018.
|- Trial web site||www.hematologie.nl|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||Dr. M.E.D. Chamuleau|
|- CONTACT for SCIENTIFIC QUERIES||Dr. M.E.D. Chamuleau|
|- Sponsor/Initiator ||VU University Medical Center|
(Source(s) of Monetary or Material Support)
|VU University Medical Center|
|- Brief summary||Study phase: Phase II.
Patients with newly diagnosed Burkitt lymphoma ≥ 18years.
To asses efficacy (PFS and OS at 2 years) and feasibility (defined as number of cyles administered on an out-patient-clinic basis) of risk-adapted DA-EPOCH-R in patients with newly diagnosed Burkitt lymphoma
A prospective, monocenter, open label, non-randomized clinical trial:
1. Low risk patients will receive 3 cycles of DA-EPOCH-RR;
2. High risk patients will receive 6 cycles of DA-EPOCH-R;
3. CSF cytology will be done in all patients;
4. High Risk patients with CSF negative will receive prophylactic intrathecal treatment;
5. Low risk patients with CSF negative (1 normal LP and no clinical suspicion) will not receive prophylactic intrathecal treatment;
6. All patients with CSF positive will receive active intrathecal treatment;
7. FDG-PET/CT pre- and post-cycle 2 in all patients. Low risk patients with positive low-dose PET/CT (positive defined as a score ≥ 3 according to Deauville criteria (appendix B1) after 2 cycles will receive 6 cycles of DA-EPOCH-R;
8. A total of 22 patients will be enrolled in the protocol.
|- Main changes (audit trail)|
|- RECORD||14-dec-2012 - 4-jan-2013|