A Randomized Study in Non-Hodgkin's Lymphoma Patients Carrying Hepatitis B Surface Antigen
|First Received Date ICMJE||September 12, 2005|
|Last Updated Date||September 13, 2005|
|Start Date ICMJE||September 2001|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||We expect to enter 33 patients per year. Taking into account 10﹪dropout rate, we may finish accrual of patients within 3 years.|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT00201318 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||A Randomized Study in Non-Hodgkin's Lymphoma Patients Carrying Hepatitis B Surface Antigen|
|Official Title ICMJE||A Randomized Study of Lamivudine Prophylaxis or Treatment Against Hepatitis B Reactivation in Non-Hodgkin's Lymphoma Patients Carrying Hepatitis B Surface Antigen|
* AIMS OF THE STUDY (STUDY OBJECTIVES)
(Study end-points: The major end-point: hepatitis B reactivation in NHL patients---defined by higher than 10-fold increase of serum HBV DNA level and/or reappearance of HBeAg in the serum during and within 6 months after chemotherapy. The minor end-point I : events of hepatic failure and death---defined by jaundice with hepatic encephalopathy. The minor end-point II: the response rate and survival rate in HBsAg-positive NHL patients receiving lamivudine prophylaxis and treatment.)
3.2 Hepatotoxicity For patients with normal prechemotherapy serum ALT, hepatitis flare-up is defined as ALT elevation greater than 1.5 fold of upper normal limit. For patients with abnormal prechemotherapy serum ALT, hepatitis flare-up is defined as 2.0 fold or greater increase of serum ALT level. The hepatitis or hepatitis flare-up is attributed to reactivation of HBV when there is a sudden elevation (＞10-fold) in serum HBV DNA level or reappearance of HBV DNA and/or HBeAg in the serum.
Since results of our previous study has indicated that nearly all clinical hepatitis developed in HBV carrier during chemotherapy is caused by HBV reactivation, and serum HBV DNA data are not readily available in most hospitals, all patients with hepatitis flare-up are considered HBV reactivation until proved otherwise. For patients in the second arm, biochemical hepatitis will prompt a start of daily lamivudine, even before a definite documentation of 10-fold increase of HBV DNA. For patients with only minor hepatic dysfunction (total bilirubin ＜3.0 mg/dl and ALT ＜200 I.U./L), full-dose chemotherapy is recommended on the scheduled treatment day without delay. For patients with more severe hepatic dysfunction (total bilirubin ≧ 3.0 mg/dl or ALT ≧ 200 I.U./L), subsequent course is postponed for 1 week and the dosage modified as followings if the values remain abnormal after 1 week:
Total Bilirubin (mg/dl) ＜3.0 3.0 ~ 4.9 5.0 ~ 7.5 ＞7.5 ALT (I.U./L) ＜200 200 ~ 399 400 ~ 800 ＞800 Doxorubicin 100% 75% 50% *
3.3 Gastrointestinal Toxicity In case of severe (≧ NCI Gr III) anorexia, nausea, vomiting, diarrhea, stomatitis or abdominal pain, all therapy should be delayed until improvement of symptoms to ≦ GrII.
Patients will be off study if ≧ Gr III 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 III during the next course, doses of cyclophosphamide and doxorubicin should be reduced by 25% in the subsequent courses. If no further episodes of severe reaction, the doses can be escalated, 12.5% each time, and back to 100%.
3.4 Cardiotoxicity In case of NCI grade II cardiotoxicity, doxorubicin should be reduced by 50%. If cardiotoxicity is resolved, the dose may be carefully deescalated, 12,5% each time, in the subsequent courses. If severe (≧ NCI grade III) cardiotoxicity develops, doxorubicin should be discontinued and should not be used again in the subsequent courses.
3.5 Multiple Toxicity In the event of multiple toxicity, dose modification should be based on the guideline that requires the greatest reduction of doses.
4.0 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:
5.0 MEASUREMENT OF EFFECT ： Authorized physicians or research nurses must call Ms. Yueh-Ling Ho at the TCOG Operations Office (Tel: 02-26534401 ext 6655) for patients registration and randomization.
A permuted block randomization will be used to generate the list by the Statistical Center housed at the Division of Biostatistics, NHRI. Treatment assignment is given only when the patient passes the eligibility check.
6.0 REPORT OF ADVERSE EFFECT : Adverse effect of treatments should be reported to TCOG Operations Office at 02-26534401 ext 6655, 6657, 6658 and FAX: 02-2782-3755, within 48 hours. See appendix for the TCOG ADR (Adverse Drug Reaction) Form of reporting adverse effect.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Condition ICMJE||Non-Hodgkin's Lymphoma|
|Intervention ICMJE||Drug: Cyclophosphamide Doxorubicin Vincristine Lamivudine|
|Study Arm (s)||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||October 2005|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||20 Years to 70 Years|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||Taiwan|
|NCT Number ICMJE||NCT00201318|
|Other Study ID Numbers ICMJE||T1401|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Health Research Institutes, Taiwan|
|Information Provided By||National Health Research Institutes, Taiwan|
|Verification Date||September 2005|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP