Clinical trial NCT01066429: DA-EDOCH14-R in Poor-prognosis Diffuse Large B-cell Lymphoma
Official title: Treatment With Infusional Dose-adjusted Etoposide/Vincristine/Doxorubicin/Bolus Cyclophosphamide/Dexamethasone and Rituximab (DA-EDOCH14-R) in Patients With Poor-prognosis Diffuse Large B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Diffuse Large B-Cell Lymphoma (DLBCL)
Keywords: poor-prognosis diffuse large B-cell lymphoma
dose-adjusted
R-EDOCH-14
rituximab
age-adjusted IPI
toxicity
Lead sponsor: Hospital Universitario Principe de Asturias
Sponsor class: OTHER
First posted: 2010-02-10
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Poor prognosis dufuse large B-cell lymphoma (DLBCL) represents 50% of all DLBCL with overall cure rates ranging from 50-60% with modern dose-dense immunochemotherapy regimens such as R-CHOP14. Using an alternative strategy, as infusional and dose-adjusted R-EPOCH, the investigators have shown an 83% of complete responses (CR), with an estimated 5-year overall survival (OS) rate of 75% (García-Suárez et al. British Journal of Haematology 2007, 136:276). Despite this improvement in outcome, the search for new treatment strategies should continue. Therefore, compared with prior R-EPOCH the investigators decided to investigate whether the introduction of dexamethasone (40 mg IV on days 1-5) in place of prednisone (based upon data which demonstrated that the former was associated with enhanced Central Nervious System penetration) and the reduction of treatment intervals from 3 to 2 weeks would be feasible and might improve the outcome in this group of patients.

Detailed description: Medication, Dose and Method for Administration:

* Rituximab: 375 mg/m2, endovenous, according to the protocol of the service, day 1 (except in the first cycle, in which it will be on day 5).
* Etoposide: 50 mg/m2/day, in continuous 24-hour infusion, days 1 to 4.
* Adriamycin: 10 mg/m2/day, in continuous 24-hour infusion of, days 1 to 4.
* Vincristine: 0.4 mg/m2/day, in continuous 24-hour infusion, days 1 to 4
* Dexamethasone: 40 mg, endovenous, days 1 to 5. Followed by prednisone 30 mg (day +6), 20 mg (day +7), and 10 mg (day +8).
* Cyclophosphamide: 750 mg/m2, endovenous, in 30 minutes, day 5, after ending the continuous infusion of adriamycin, etoposide and vincristine.
* MESNA (If the dose of Cyclophosphamide is \> 1 g/m2

Eligibility criteria: Inclusion Criteria:

* Signing the Informed Consent.
* Histology: diffuse large B-cell lymphoma de novo (primary mediastinal B-cell lymphomas will be included provided that they have a mass greater than 7 cm in larger diameter) and follicular NHL grade 3b.
* aaIPI: 2-3.
* Age: Between 18 and 70 years.
* General Condition (ECOG/WHO): Proper organic function, defined by: FEVI ≥ 40%, serum creatinine \< 150 µmol/L, serum bilirubin \< 30 µmol/L, control of other medical conditions such as: infection, leukocytes ≥ 3.5 x 109/l and platelets ≥ 100 x 109/l (except if they are caused by lymphomatous infiltration of bone marrow or of the spleen).

Exclusion Criteria:

* HIV-positive.
* Pregnancy or breastfeeding.
* Serious disease compromising the performance of the therapeutic regimen.
* Recent history of another malignant disease (except skin cancer different from melanoma or carcinoma in-situ of the cervix), prior radiotherapy or chemotherapy, history of indolent lymphoma.
* CNS infiltration at diagnosis.

Primary outcomes:
measure: efficacy of the EDOCH14-R scheme at an adjusted dose
timeFrame: Between December 2009 and January 2012
Secondary outcomes:
measure: hematological and extra-hematological toxicity of the EDOCH14-R scheme
timeFrame: Between december 2009 and January 2012
Other outcomes:
Locations:
city: Alcala de Henares
country: Spain
facility: Principe de Asturias University Hospital
state: Madrid
Study officials:
affiliation: Service of Hematology, Principe de Asturias University Hospital,
name: Julio Garcia-Suarez, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Garcia-Suarez J, Flores E, Callejas M, Arribas I, Gil-Fernandez JJ, Olmedilla G, Curto N, Guillen H, Casco CR, Martin Y, Burgaleta C. Two-weekly dose-adjusted (DA)-EPOCH-like chemotherapy with high-dose dexamethasone plus rituximab (DA-EDOCH14-R) in poor-prognostic untreated diffuse large B-cell lymphoma. Br J Haematol. 2013 Feb;160(4):510-4. doi: 10.1111/bjh.12144. Epub 2012 Dec 11.