Ignite Creation Date:
2024-05-05 @ 4:34 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00262210
Status:
COMPLETED
Last Update Posted:
2005-12-06
First Post:
2005-12-05
Brief Title:
A Comparative Study for Non-Hodgkins Lymphoma in Hepatitis B Virus Carriers
Sponsor:
National Health Research Institutes Taiwan
Organization:
National Health Research Institutes Taiwan
Study Overview
Official Title:
A Comparative Study for Non-Hodgkins Lymphoma in Hepatitis B Virus Carriers
Status:
COMPLETED
Status Verified Date:
2005-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
AIMS OF THE STUDY
1 To test if steroid-free chemotherapeutic regimens decrease the risk of HBV reactivation and hepatitis development in HBsAg carriers
2 To compare the efficacy of steroid-free chemotherapeutic regimens with that of steroid-containing regimens in terms of lymphoma control
3 To study the change of activity of HBV and other hepatotropic viruses during the course of chemotherapy
1 To test if steroid-free chemotherapeutic regimens decrease the risk of HBV reactivation and hepatitis development in HBsAg carriers
2 To compare the efficacy of steroid-free chemotherapeutic regimens with that of steroid-containing regimens in terms of lymphoma control
3 To study the change of activity of HBV and other hepatotropic viruses during the course of chemotherapy
Detailed Description:
TREATMENT PLANS FOR FIRST-LINE AND SECOND LINE CHEMOTHERAPY
1 First-line Chemotherapy 11 PACE and ACE Treatment Scheme of PACE and ACE Cyclophosphamide 650 mgm2 iv Day 1 Epirubicin 60 mgm2 iv Day 1 Etoposide 55 mgm2d iv Day 1-3 Prednisolone 60 mgm2d po Day 1-7
For ACE prednisolone is omitted 12 Courses will be repeated every 21 days 13 For patients with CR give at least 2 additional courses for a minimum of 6 courses
14 For patients with PR or SD may change to second-line chemotherapy if no further tumor shrinkage between two consecutive coursesLocal radiotherapy is allowed for residual localized tumors
15 For patients with PD change to second-line chemotherapy
2 Second-line Chemotherapy For patients who have failed steroid-containing or steroid- free chemotherapy respective steroid-containing and steroid-free salvage chemotherapy should be used
21 VIMP and VIM Treatment Scheme of VIMP and VIM VP-16 100 mgm2d iv Day 135 Ifosfamide 1 gmm2d iv Day 1-5 MTX 30 mgm2d iv Day 15 Prednisolone 60 mgm2d PO Day 1-7
For VIM prednisolone is omitted Repeated every 21 days
Mesna for urinary tract protection is needed
Mesna 100 mgm2 is bolus injected immediately before the infusion of first-day ifosfamide and then 500mgm2day is infused for 5 day with ifosfamide
22 Infusional CDE P ICDE P and Infusional CDE ICDE Treatment Scheme of ICDEP and ICDE Cyclophosphamide 1875 mgm2d continuous iv infusion Day 1-4 Epirubicin 20 mgm2d continuous iv infusion Day 1-4 Etoposide 60 mgm2d continuous iv infusion Day 14 Prednisolone 60 mgm2d PO Day 1-7
For ICDE prednisolone is omitted Repeated every 21 days
Cyclophosphamide and epirubicin can be mixed in a 500ml of 5 DW and infused together Etoposide is dissolved in another 500ml of 5 DW and infused in a separate line
30 DOSE MODIFICATION 31 Hematological Toxicity
Drug administration is postponed one week if there is no full hematological recovery AGC 2000mm3 and Platelet 100000mm3 from prior course at scheduled treatment day Full doses will be given as soon as the hematological recovery is documented If after another one week ie two weeks after the due day recovery is still incomplete the treatment may be started and the dosage of the drugs be reduced according to the following schedule for all regimens
AGCmm3Plateletmm3 1500-200075000-100000 1000-149950000-74999 100050000 Cyclophosphamide 80 60 Epirubicin 80 60 VP-16 80 60 Ifosfamide 80 60 MTX 80 60
Growth factors G-CSF GM-CSF are allowed to be used for patients with prolonged myelosuppression but should not influence the schedule of dose- modification as illustrated above
Postpone for another week If the counts remain AGC 1000 or Platelet 50000 growth factors may be used at this juncture ie 2 weeks after due day Patients should be off study if still AGC 1000 or Platelet 50000 3 weeks after the due day
32 Hepatotoxicity For patients with normal or abnormal prechemotherapy serum ALT hepatitis or hepatitis flare-up is defined as a threefold or greater increase in serum ALT level that exceeds 100 IUL The hepatitis or hepatitis flare-up is attributed to reactivation of chronic hepatitis B when there is a sudden elevation 10-fold in serum HBV DNA level or reappearance of HBV DNA or HBeAg in the serum
Since serum HBV DNA data is not readily available in most hospitals all patients with hepatitis or hepatitis flare-up are considered as HBV reactivation until proved otherwise Cross-over to steroid-free arm for subsequent treatment is not allowed in this study For patients with only minor hepatic dysfunction Total Bilirubin 30 mgdl and ALT 200 IUL full-dose chemotherapy is recommended on the scheduled treatment date without delay For patients with more severe hepatic dysfunction total bilirubin 30 mgdl or ALT 200 IUL subsequent course is postponed for 1 week and the dosage modified as followings if the values remain abnormal after 1 week
Total Bilirubin mgdl 30 30 - 49 50 - 75 75 ALT IUL 200 200 - 399 400 - 800 800 Epirubicin 100 75 50
Wait until recovery with serum levels below these values Patients will be off study if Bil 75 or ALT 800 3 weeks after the due day
33 Gastrointestinal Toxicity In case of severe ECOG grade III anorexia nausea vomiting diarrhea stomatitis or abdominal pain all therapy should be delayed until improvement of symptoms to GrII
Patient will be off study if GrIII toxicity persists 3 weeks after due day Patients are allowed to use H3-blockers in the subsequent courses for severe nausea and vomiting If gastrointestinal toxicity is still Gr II during the next course doses of cyclophosphamide epirubicin and VP-16 should be reduced by 25 in the subsequent courses If no further episodes of severe reaction the doses can be escalated back to 100
34 Cardiotoxicity In case of ECOG grade II cardiotoxicity epirubicin should be reduced by 50 If cardiotoxicity resolved the dose may be carefully escalated ie increase 10-25 of dose each time in the subsequent courses If severe ECOG grade III cardiotoxicity develops epirubicin should be discontinued and should not be used again in the subsequent courses
35 In the event of multiple toxicities dose modification should be made based on the guideline that requires the greatest reduction of doses
4 CRITERIA FOR REMOVAL FROM STUDY
All patients who are still under or have completed protocol treatments 1st-line or 2nd-line should be continuously followed-up for all study end points Patients are removed from study if they have major violation of the protocol due to the following reasons
41 Refuse treatment 42 Unable to receive due treatments either because of severe toxicity or other reasons
43 Inadvertent cross-over to opposite arms steroid-containing or steroid-free of treatment
1 First-line Chemotherapy 11 PACE and ACE Treatment Scheme of PACE and ACE Cyclophosphamide 650 mgm2 iv Day 1 Epirubicin 60 mgm2 iv Day 1 Etoposide 55 mgm2d iv Day 1-3 Prednisolone 60 mgm2d po Day 1-7
For ACE prednisolone is omitted 12 Courses will be repeated every 21 days 13 For patients with CR give at least 2 additional courses for a minimum of 6 courses
14 For patients with PR or SD may change to second-line chemotherapy if no further tumor shrinkage between two consecutive coursesLocal radiotherapy is allowed for residual localized tumors
15 For patients with PD change to second-line chemotherapy
2 Second-line Chemotherapy For patients who have failed steroid-containing or steroid- free chemotherapy respective steroid-containing and steroid-free salvage chemotherapy should be used
21 VIMP and VIM Treatment Scheme of VIMP and VIM VP-16 100 mgm2d iv Day 135 Ifosfamide 1 gmm2d iv Day 1-5 MTX 30 mgm2d iv Day 15 Prednisolone 60 mgm2d PO Day 1-7
For VIM prednisolone is omitted Repeated every 21 days
Mesna for urinary tract protection is needed
Mesna 100 mgm2 is bolus injected immediately before the infusion of first-day ifosfamide and then 500mgm2day is infused for 5 day with ifosfamide
22 Infusional CDE P ICDE P and Infusional CDE ICDE Treatment Scheme of ICDEP and ICDE Cyclophosphamide 1875 mgm2d continuous iv infusion Day 1-4 Epirubicin 20 mgm2d continuous iv infusion Day 1-4 Etoposide 60 mgm2d continuous iv infusion Day 14 Prednisolone 60 mgm2d PO Day 1-7
For ICDE prednisolone is omitted Repeated every 21 days
Cyclophosphamide and epirubicin can be mixed in a 500ml of 5 DW and infused together Etoposide is dissolved in another 500ml of 5 DW and infused in a separate line
30 DOSE MODIFICATION 31 Hematological Toxicity
Drug administration is postponed one week if there is no full hematological recovery AGC 2000mm3 and Platelet 100000mm3 from prior course at scheduled treatment day Full doses will be given as soon as the hematological recovery is documented If after another one week ie two weeks after the due day recovery is still incomplete the treatment may be started and the dosage of the drugs be reduced according to the following schedule for all regimens
AGCmm3Plateletmm3 1500-200075000-100000 1000-149950000-74999 100050000 Cyclophosphamide 80 60 Epirubicin 80 60 VP-16 80 60 Ifosfamide 80 60 MTX 80 60
Growth factors G-CSF GM-CSF are allowed to be used for patients with prolonged myelosuppression but should not influence the schedule of dose- modification as illustrated above
Postpone for another week If the counts remain AGC 1000 or Platelet 50000 growth factors may be used at this juncture ie 2 weeks after due day Patients should be off study if still AGC 1000 or Platelet 50000 3 weeks after the due day
32 Hepatotoxicity For patients with normal or abnormal prechemotherapy serum ALT hepatitis or hepatitis flare-up is defined as a threefold or greater increase in serum ALT level that exceeds 100 IUL The hepatitis or hepatitis flare-up is attributed to reactivation of chronic hepatitis B when there is a sudden elevation 10-fold in serum HBV DNA level or reappearance of HBV DNA or HBeAg in the serum
Since serum HBV DNA data is not readily available in most hospitals all patients with hepatitis or hepatitis flare-up are considered as HBV reactivation until proved otherwise Cross-over to steroid-free arm for subsequent treatment is not allowed in this study For patients with only minor hepatic dysfunction Total Bilirubin 30 mgdl and ALT 200 IUL full-dose chemotherapy is recommended on the scheduled treatment date without delay For patients with more severe hepatic dysfunction total bilirubin 30 mgdl or ALT 200 IUL subsequent course is postponed for 1 week and the dosage modified as followings if the values remain abnormal after 1 week
Total Bilirubin mgdl 30 30 - 49 50 - 75 75 ALT IUL 200 200 - 399 400 - 800 800 Epirubicin 100 75 50
Wait until recovery with serum levels below these values Patients will be off study if Bil 75 or ALT 800 3 weeks after the due day
33 Gastrointestinal Toxicity In case of severe ECOG grade III anorexia nausea vomiting diarrhea stomatitis or abdominal pain all therapy should be delayed until improvement of symptoms to GrII
Patient will be off study if GrIII toxicity persists 3 weeks after due day Patients are allowed to use H3-blockers in the subsequent courses for severe nausea and vomiting If gastrointestinal toxicity is still Gr II during the next course doses of cyclophosphamide epirubicin and VP-16 should be reduced by 25 in the subsequent courses If no further episodes of severe reaction the doses can be escalated back to 100
34 Cardiotoxicity In case of ECOG grade II cardiotoxicity epirubicin should be reduced by 50 If cardiotoxicity resolved the dose may be carefully escalated ie increase 10-25 of dose each time in the subsequent courses If severe ECOG grade III cardiotoxicity develops epirubicin should be discontinued and should not be used again in the subsequent courses
35 In the event of multiple toxicities dose modification should be made based on the guideline that requires the greatest reduction of doses
4 CRITERIA FOR REMOVAL FROM STUDY
All patients who are still under or have completed protocol treatments 1st-line or 2nd-line should be continuously followed-up for all study end points Patients are removed from study if they have major violation of the protocol due to the following reasons
41 Refuse treatment 42 Unable to receive due treatments either because of severe toxicity or other reasons
43 Inadvertent cross-over to opposite arms steroid-containing or steroid-free of treatment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None