Large B-cell Diffuse Lymphoma of Testis
Conditions
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.
Interventions
DRUGRituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone, liposomal cytarabine, methotrexate
Weeks 1-15: * 6 cycles of CHOP on Days 1 to 5, to be repeated q21 Days * Rituximab 375 mg/m2 on Day 0 or Day 1 of every CHOP cycle * IT chemoth:Depocyte 50 mg on Day 0 of cycles 2,3,4&5 of R-CHOP Weeks 18-22: • Methotrexate 1.5 g/m2 q14 Days x 2 From Week 24: • Scrotal prophylactic radiotherapy or involved field radiotherapy(but can be planned concomitantly to R-CHOP in pts with bilateral disease)
Sponsors
International Extranodal Lymphoma Study Group (IELSG)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events Assessment | 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 | Number of patients who withdrew the treatment due to adverse event |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 5 Year Cumulative Incidence of Progressions | From the first documented response to relapse until 5 years from study entry | Percentage of patients with disease progression after achieving a remission |
| 5 Years Progression Free Survival (PFS) | From study entry until 5 years after | Percentage of patients free from disease progression after 5 years from study entry |
| 5 Years Overall Survival (OS) | From study entry until 5 years after | Percentage of patients alive after 5 years from study entry |
Countries
Italy, Switzerland
Participant flow
Recruitment details
Recruitment lasted from 27 September 2009 to 13 July 2017
Participants by arm
| Arm | Count |
|---|---|
| R-CHOP, Depocyte, Methotrexate Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone, liposomal cytarabine, methotrexate: Weeks 1-15:
* 6 cycles of CHOP on Days 1 to 5, to be repeated q21 Days
* Rituximab 375 mg/m2 on Day 0 or Day 1 of every CHOP cycle
* IT chemoth:Depocyte 50 mg on Day 0 of cycles 2,3,4&5 of R-CHOP
Weeks 18-22:
• Methotrexate 1.5 g/m2 q14 Days x 2
From Week 24:
• Scrotal prophylactic radiotherapy or involved field radiotherapy(but can be planned concomitantly to R-CHOP in pts with bilateral disease) | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Second malignancy | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | R-CHOP, Depocyte, Methotrexate | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 27 Participants | — |
| Age, Categorical Between 18 and 65 years | 27 Participants | — |
| Age, Continuous | 66 years | — |
| Ann Arbor stage Stage I | 32 Participants | — |
| Ann Arbor stage Stage II | 22 Participants | — |
| Bilateral testicular location Bilateral testicular location | 1 Participants | — |
| Bilateral testicular location No bilateral testicular location | 53 Participants | — |
| B symptoms No Presence of B symptoms | 52 Participants | — |
| B symptoms Presence of B symptoms | 2 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Italy | 47 participants | — |
| Region of Enrollment Switzerland | 7 participants | — |
| Serum Beta2-microglobulin </= normal upper value | 40 Participants | — |
| Serum Beta2-microglobulin > normal upper value | 8 Participants | — |
| Serum Beta2-microglobulin Not recorded | 6 Participants | — |
| Serum lactate dehydrogenase (LDH) </= normal upper value | 47 Participants | — |
| Serum lactate dehydrogenase (LDH) > normal upper value | 7 Participants | — |
| Sex: Female, Male Female | 0 Participants | — |
| Sex: Female, Male Male | 54 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 12 / 54 | 0 / 54 | 0 / 48 |
| other Total, other adverse events | 47 / 54 | 47 / 54 | 17 / 48 |
| serious Total, serious adverse events | 19 / 54 | 17 / 54 | 3 / 48 |
Outcome results
Primary
Adverse Events Assessment
Number of patients who withdrew the treatment due to adverse event
Time frame: 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
Population: Weeks 1 -15 All patients treated with 6 cycles of R-CHOP (CHOP21) on days 0/1 to 5, to be repeated every 21 days Intratecal (IT) Chemotherapy: liposomal cytarabine on day 0 of cycles 2, 3, 4 and 5 of R-CHOP Weeks 18 - 22 High Dose (HD) Methotrexate (MTX) Days 0 - 4 of two 14 days cycles From Week 25 Scrotal prophylactic radio therapy (RT) to the contralateral testis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| R-CHOP, Depocyte, Methotrexate | Adverse Events Assessment | 6 Participants |
| R-CHOP + Lyposomal Cytarabine | Adverse Events Assessment | 3 Participants |
| HD-MTX | Adverse Events Assessment | 3 Participants |
Secondary
5 Year Cumulative Incidence of Progressions
Percentage of patients with disease progression after achieving a remission
Time frame: From the first documented response to relapse until 5 years from study entry
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R-CHOP, Depocyte, Methotrexate | 5 Year Cumulative Incidence of Progressions | 6 percentage of participants |
Secondary
5 Years Overall Survival (OS)
Percentage of patients alive after 5 years from study entry
Time frame: From study entry until 5 years after
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R-CHOP, Depocyte, Methotrexate | 5 Years Overall Survival (OS) | 92 percentage of participants |
Secondary
5 Years Progression Free Survival (PFS)
Percentage of patients free from disease progression after 5 years from study entry
Time frame: From study entry until 5 years after
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R-CHOP, Depocyte, Methotrexate | 5 Years Progression Free Survival (PFS) | 91 percentage of participants |