Clinical trial NCT00945724: Safety and Feasibility Study of Combination of State of Art Chemoimmunotherapy, Intensive Central Nervous System Prophylaxis and Scrotal Irradiation to Treat Primary Diffuse Large B-cell Lymphoma of Testis
Official title: A Phase II Study of R-CHOP With Intensive CNS Prophylaxis and Scrotal Irradiation in Patients With Primary Testicular Diffuse Large B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Large B-cell Diffuse Lymphoma of Testis
Lead sponsor: International Extranodal Lymphoma Study Group (IELSG)
Sponsor class: OTHER
First posted: 2009-07-24
Enrollment: 54
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial is a phase II non-comparative study aimed to determine the feasibility and toxicity of the R-CHOP regimen in combination with intrathecal liposomal cytarabine and systemic intermediate-dose methotrexate followed by loco-regional radiotherapy.


Eligibility criteria: Inclusion Criteria:

1. Patients with primary testicular lymphoma at diagnosis. Histological subtype included into the study is only Diffuse Large B Cell Lymphoma (Attachment 2: WHO classification of lymphoma).
2. Orchiectomy is mandatory, before enrolment of the patient into the study.
3. Orchiectomy should be performed within 2 months before study entry.
4. Age 18-80
5. Untreated patients
6. Ann Arbor Stage IE and IIE. Bilateral testicular involvement at presentation will not be considered Stage IV. These patients may be included into the study and the final Ann Arbor stage (I or II) will be determined by the extent of nodal disease.
7. Bidimensionally measurable or evaluable disease. Patients who have had all disease removed by surgery are eligible.
8. Adequate haematological counts: ANC \> 1.0 x 109/L and PLTs count \> 75 x 109/L
9. Cardiac ejection fraction ≥ 45% by MUGA scan or echocardiography
10. Non peripheral neuropathy or any active non-neoplastic CNS disease.
11. No other major life-threatening illnesses that may preclude chemotherapy
12. Conjugated bilirubin ≤ 2 x ULN.
13. Alkaline phosphatase and transaminases ≤ 2 x ULN.
14. Creatinine clearances ≥ 45 ml/min.
15. HIV negativity
16. HBV negativity or patients with HBVcAb +, HbsAg -, HBs Ab+/- with HBV-DNA negative
17. HCV negativity with the exception of patients with no signs of active chronic hepatitis histologically confirmed
18. Life expectancy \> 6 months.
19. Performance status \< 2 according to ECOG scale.
20. No psychiatric illness that precludes understanding concepts of the trial or signing informed consent
21. Written informed Consent

Exclusion Criteria:

1. Has known or suspected hypersensitivity or intolerance to rituximab
2. History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances
3. Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug)
4. Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 5, NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
5. History of clinically relevant hypotension
6. CNS involvement (meningeal and/or brain involvement by lymphoma)
7. Evolving malignancy within 3 years with the exception of localized non-melanomatous skin cancer
8. HIV positivity
9. HBV positivity with the exception of patients with HBVcAb +, HbsAg -, HBs Ab+/- with HBV-DNA negative
10. HCV positivity with the exception of patients with no signs of active chronic hepatitis histologically confirmed
11. Active opportunistic infection
12. Receipt of extensive radiation therapy, systemic chemotherapy, or other antineoplastic therapy
13. Exposure to Rituximab prior study entry
14. Have received an experimental drug or used an experimental medical device within 4 weeks before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study.
15. Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent

Primary outcomes:
measure: Adverse Events Assessment
timeFrame: From treatment start until the last drug administration, up to week 22 for the 'R-CHOP, Depocyte, Methotrexate' Group, up to 15 weeks (Weeks 1-15) for the 'R-CHOP + Lyposomal Cytarabine' Group, and from week 18-22 for the 'HD-MTX' Group
Secondary outcomes:
measure: 5 Year Cumulative Incidence of Progressions
timeFrame: From the first documented response to relapse until 5 years from study entry
measure: 5 Years Progression Free Survival (PFS)
timeFrame: From study entry until 5 years after
measure: 5 Years Overall Survival (OS)
timeFrame: From study entry until 5 years after
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: A.O. SS. Antonio e Biagio e Cesare Arrigo
city: Brescia
country: Italy
facility: Spedali Civili
city: Cagliari
country: Italy
facility: Ematologia Ospedale Businco
city: Genova
country: Italy
facility: S. Martino Hospital
city: Milan
country: Italy
facility: European Institute of Oncology
city: Milan
country: Italy
facility: San Raffaele H Scientific Institute
city: Modena
country: Italy
facility: Policlinico
city: Monza
country: Italy
facility: A.O. San Gerardo
city: Novara
country: Italy
facility: AOU Maggiore della Carità
city: Pavia
country: Italy
facility: S. Matteo
city: Piacenza
country: Italy
facility: Ospedale Civile
city: Ravenna
country: Italy
facility: U.O. Ematologia AUSL Ravenna
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova
city: Roma
country: Italy
facility: IFO Regina Elena
city: Roma
country: Italy
facility: Policlinico Universitario Campus Biomedico
city: Rome
country: Italy
facility: Università La Sapienza
city: Rozzano
country: Italy
facility: Humanitas
city: Sassari
country: Italy
facility: Azienda Ospedaliero-Universitaria
city: Terni
country: Italy
facility: A.O. S. Maria
city: Torino
country: Italy
facility: A.O.U. San Giovanni Battista-Molinette, S.C. Ematologia 2
city: Varese
country: Italy
facility: Ospedale di Circolo Fondazione Macchi
city: Bellinzona
country: Switzerland
facility: IOSI
Study officials:
affiliation: IOSI
name: Emanuele Zucca, MD
role: STUDY_CHAIR
References: