Viewing Study NCT00201318



Ignite Creation Date: 2024-05-05 @ 12:00 PM
Last Modification Date: 2024-10-26 @ 9:18 AM
Study NCT ID: NCT00201318
Status: COMPLETED
Last Update Posted: 2005-09-20
First Post: 2005-09-12

Brief Title: A Randomized Study in Non-Hodgkins Lymphoma Patients Carrying Hepatitis B Surface Antigen
Sponsor: National Health Research Institutes Taiwan
Organization: National Health Research Institutes Taiwan

Study Overview

Official Title: A Randomized Study of Lamivudine Prophylaxis or Treatment Against Hepatitis B Reactivation in Non-Hodgkins Lymphoma Patients Carrying Hepatitis B Surface Antigen
Status: COMPLETED
Status Verified Date: 2005-09
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 STUDY OBJECTIVES

1 To test the effect of daily lamivudine 100 mg in reducing the risk of HBV reactivation and hepatitis development in HBsAg NHL patients
2 To test the efficacy of daily lamivudine in preventing and treating hepatitis B reactivation and in circumventing hepatic failure and death
3 To test whether lamivudine can improve the overall outcome of NHL patients who are HBV carriers

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 andor 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
Detailed Description: TREATMENT PLANS

1 Systemic chemotherapy with CHOP regimen Schedule and Dose for CHOP Cyclophosphamide 750 mgm2 iv Day 1 Doxorubicin 50 mgm2 iv Day 1 Vincristine 14 mgm2d iv Day 1 Prednisolone 60 mgm2d po Day 1-7 11 Courses will be repeated every 21 days 12 For patients with CR give at least 2 additional courses for a minimum of 6 courses

13 For patients with maximal response as PR or SD change to second-line chemotherapy The regimens for second-line chemotherapy are at the discretion of the investigators Local radiotherapy is allowed for residual localized 14 For patients with PD change to second-line chemotherapy The regimens of the latter are at the discretion of the investigators

21 Arm I Patients take lamivudine 100 mg PO qd starting from Day 1 of the first course of CHOP and until 2 months after the completion of chemotherapy Lamivudine is to be maintained no matter hepatitis occurred or not during chemotherapy If second-line chemotherapy is used lamivudine with the same dose and schedule will be continued until 2 months after completion of the second-line chemotherapy

If third-line chemotherapy is needed the use of lamivudine will be at the 22 Arm II Patients are treated with CHOP alone If the patients develop clinical hepatitis as defined in section 72 lamivudine 100 mg PO qd will be given and continued until hepatitis is resolved Prophylactic lamivudine is not to be given in subsequent chemotherapy Our previous study has indicated that nearly all clinical hepatitis developed in HBV carriers during systemic chemotherapy is caused by HBV reactivation Therefore for practical reason the investigators are not advised to wait for the results of HBV DNA serology examination before starting lamivudine treatment

30 DOSE MODIFICATION 31 Hematological Toxicity Drug administration is postponed 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 two weeks after the due day recovery is still incomplete the treatment may be started and the dosage be reduced according to the following

schedule

AGCmm3Plateletmm3 1500-200075000-100000 1000-149950000-74999 100050000 Cyclophosphamide 80 60 Doxorubicin 80 60
G-CSF is allowed to be used prophylactically for older 60 years old patients and for patients with previous or ongoing prolonged myelosuppression

Postpone for another week If the counts remain AGC1500 or Platelet 75000 three weeks after the due day patients should be off study

32 Hepatotoxicity For patients with normal prechemotherapy serum ALT hepatitis flare-up is defined as ALT elevation greater than 15 fold of upper normal limit For patients with abnormal prechemotherapy serum ALT hepatitis flare-up is defined as 20 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 andor 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 30 mgdl and ALT 200 IUL full-dose chemotherapy is recommended on the scheduled treatment day 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 Doxorubicin 100 75 50

Wait until recovery with serum levels below these values Patients will be off study if Bil 75 mgdl or ALT 800 IUL 3 weeks after the due day

33 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 125 each time and back to 100

34 Cardiotoxicity In case of NCI grade II cardiotoxicity doxorubicin should be reduced by 50 If cardiotoxicity is resolved the dose may be carefully deescalated 125 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

35 Multiple Toxicity In the event of multiple toxicity dose modification should be based on the guideline that requires the greatest reduction of doses

40 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

1 Completion of assigned therapy and observation
2 Progressive of disease
3 Excessive of complication or toxicity
4 Patient death
5 Patient withdrawal or refusal

50 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

60 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 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