Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Interferons

Peginterferon α-2b 35 μg, weekly, subcutaneous (SC), until disease progression or relapse, or for up to a maximum of 5 years.

Participants will be observed and will receive no treatment.

Peginterferon

This study aims to assess the efficacy of peginterferon α-2b, compared to a control arm not receiving any maintenance treatment, in adult subjects with multiple myeloma who have responded to a prior induction therapy. Peginterferon α-2b will be given once weekly as an injection until disease progression or relapse, or for up to a maximum of 5 years (whichever occurs first).

Peginterferon α-2b as a Maintenance Therapy in Participants With Multiple Myeloma Who Responded to Induction Therapy (P01972-AM7)

Phase III Randomized, Prospective Multi-center Trial of PEG-Interferon α-2b as a Maintenance Therapy, Compared to Observation, in Patients With Multiple Myeloma Who Responded to Induction Therapy (Protocol No P01972)

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php

PFS was defined as response duration while on maintenance therapy. It was the length of time during and after treatment in which a participant was living with the cancer that did not get worse.

PFS was calculated from the date of randomization to the date of the first documented tumor progression or relapse.

OS was calculated from the date of randomization to the date of death for any

cause. Participants alive at the end of study were censored at the last date they were known to be alive. Participants who were still living at the end of the study were censored on the last date they were known to be alive.

CR was defined as:

* Absence of the original monoclonal paraprotein in serum and urine by immunofixation, maintained for a minimum of 6 weeks;
* \<5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy, if biopsy was performed.
* No increase in size or number of lytic bone lesions (development of a compression fracture did not include response);
* Disappearance of soft tissue plasmocytomas.

PR was defined as:

* At least 50% reduction in the level of the serum monoclonal paraprotein, maintained for a minimum of 6 weeks;
* Reduction in 24-hour urinary light chain excretion either by ≥ 90% or to \< 200 mg, maintained for a minimum of 6 weeks;
* For patients with non-secretory myeloma only, ≥ 50% reduction in plasma cells in a bone marrow aspirate and on a trephine biopsy, if biopsy was performed, maintained for a minimum of 6 weeks;
* At least 50% reduction in the size of soft tissue plasmacytomas;
* No increase in size or number of lytic bone lesions.

MR was defined as:

* A 25-49% reduction in the level of the serum monoclonal paraprotein maintained for a minimum of 6 weeks;
* Reduction in the 24-hour urinary light chain excretion, which still exceeded 200mg/24 hours, maintained for a minimum of 6 weeks;
* For patients with non-secretory myeloma only, 25-49% reduction in plasma cells in a bone marrow aspirate and on a trephine biopsy, if biopsy was performed, maintained for a minimum of 6 weeks;
* A 25-49% reduction in the size of soft tissue plasmacytomas;
* No increase in the size or number of lityc lesions.

PD (for patients not in CR) required one or more of the following:

* 25% increase in serum monoclonal paraprotein level, 24-hour urinary light chain excretion, or plasma cells;
* Increase in size of existing or development of new bone lesions/soft tissue plasmacytomas;
* Development of hypercalcemia.

Relapse from CR required at least one of the following:

* Reappearance of serum or urinary paraprotein;
* \>5% plasma cells;
* Development of new lytic bone lesions or soft tissue plasmacytomas or increase in the size of residual bone lesions;
* Development of hypercalcemia.

Participants were given the Europen Organization for Research in Cancer Therapy Quality of Life Questionnaire (EORTC QLQ), version 2.0, which consisted of 30 questions. The questionnaire evaluated global health/quality of life and incorporated five functional scales (Physical; Role; Emotional; Cognitive; Social). All of the scales ranged in score from 0 (worst) to 100 (best).

Merck Sharp & Dohme LLC

Tables contain both treatment-emergent events (events that occurred after receiving study drug) and non-treatment emergent events (events that occurred prior to receiving study drug).

Peginterferon α-2b

Participants were observed and received no treatment

No Treatment

Total

Age was for the intent-to-treat population (those who received at least one dose of study drug)

Age, Continuous

Gender was for the intent-to-treat population (those who received at least one dose of study drug)

Sex: Female, Male

Italy

Region of Enrollment

Senior Vice President, Global Clinical Development

Intent-to-treat population (those who received at least one dose of study drug)

Number of Days With Progression Free Survival (PFS)

Number of Days of Overall Survival (OS)

Month 9

Month 18

Number of Participants With Complete Response (CR) to Treatment

Number of Participants With Partial Response (PR) to Treatment

Number of Participants With Minimal Response (MR) to Treatment

Number of Participants With Progressive Disease(PD) or Relapse From CR

Global Score (baseline)

Global Score (last observation)

Global Score (change)

Physical Functioning Score (baseline)

Physical Functioning Score (last observation)

Physical Functioning Score (change)

Role Functioning Score (baseline)

Role Functioning Score (last observation)

Role Functioning Score (change)

Emotional Functioning Score (baseline)

Emotional Functioning Score (last observation)

Emotional Functioning Score (change)

Cognitive Functioning Score (baseline)

Cognitive Functioning Score (last observation)

Cognitive Functioning Score (change)

Social Functioning Score (baseline)

Social Functioning Score (last observation)

Social Functioning Score (change)

Intent-to-treat population (those who received at least one dose of study drug).

The number of participants analyzed varied depending on the number of observations available for each category.

Quality of Life

Overall Study

Digestive System Diseases

Infections

Symptoms and General Pathology

Carcinoma

Carcinoma, Hepatocellular

Hepatitis A

Hepatitis

Hepatitis B

Hepatitis B, Chronic

Liver Neoplasms

Hepatitis, Chronic

Liver Diseases

Gastrointestinal Diseases

Hepatitis, Viral, Human

Virus Diseases

Communicable Diseases

Enterovirus Infections

Picornaviridae Infections

RNA Virus Infections

Blood-Borne Infections

Hepadnaviridae Infections

DNA Virus Infections

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Hematinics

Amino Acids

Liver Extracts

Peginterferon alfa-2b

Antiviral Agents

Alanine

Peginterferon alfa-2b Injection combined Nucleos (t) ide Analogue therapy

1.Peginterferon alfa-2b injection: 180μg, subcutaneously inject, once a week, from week 1 to Week 48.

2, NAs: Dose please follow the approved dosage, once daily, from the first day until when discontinuation is indicated.

NAs Discontinuation Criteria: A total course of treatment is recommended for at least 4 years, and discontinuation may be considered if HBV DNA is below the lower limit of detection, Alanine aminotransferase renormalization, and HBeAg serological conversion, and remain unchanged (test every 6 months) during a consolidation therapy for at least 3 years. However, a prolonged course of treatment may reduce relapse.

Peginterferon alfa-2b Injection, Nucleos (t) ide Analogue

NAs: Dose please follow the approved dosage, once daily, from the first day until when discontinuation is indicated.

NAs Discontinuation Criteria: A total course of treatment is recommended for at least 4 years, and discontinuation may be considered if HBV DNA is below the lower limit of detection, Alanine aminotransferase renormalization, and HBeAg serological conversion, and remain unchanged (test every 6 months) during a consolidation therapy for at least 3 years. However, a prolonged course of treatment may reduce relapse.

Nucleos(t)ide analogue

Qing Xie, Ph.D

Yilan Zeng

Yi Li

Yuan Guo

Qing Xie

Jie Xu

Qin Zhang

Chuanwu Zhu

Lijuan Ouyang

Weifeng Zhao

China's new cases and deaths of hepatocellular carcinoma (HCC) rank first in the world. hepatocellular carcinoma is the third most morbid, second-most mortal malignancy in China. Up to 80% of hepatocellular carcinoma patients caused by HBV infection. Antiviral therapy can significantly reduce the incidence and mortality of hepatocellular carcinoma in patients with chronic hepatitis B (CHB), hinder the progression of liver disease, and effectively control the disease. However, studies in recent years have found that long-term therapy with Nucleos(t)ide analogue (NAs) cannot completely eliminate the risk of liver cancer in patients with chronic hepatitis B. In addition, a number of retrospective studies at home and abroad have shown that compared with long-term oral NAs, peginterferon can significantly reduce the risk of hepatocellular carcinoma in patients with chronic hepatitis B. However, there is limit prospective studies.

This multicenter, randomized, open-label, controlled trial study is aim to evaluate the pegylated interferon alfa-2b injection in comparing to NAs in reducing the incidence of hepatocellular carcinoma, to provide evidences for new management and treatment strategy options for improving clinical outcomes for the chronic hepatitis B patients. About 267 chronic hepatitis patients with intermediate to high risk of liver cancer who are now receiving nucleoside therapy will be enrolled. Subjects will be randomized into the peginterferon combined NAs group and the NAs monotherapy group at a ratio of 2:1. Level of HBsAg, proportion of patients with HBsAg clearance and seroconversion, incidence of liver cirrhosis and hepatocellular carcinoma will be assessed.

A Prospective Study to Evaluate Peginterferon in Reducing the Incidence of HCC in CHB Patients

A Prospective, Randomized, Open-label, Multicenter Study to Evaluate the Peginterferon, Comparing to Nucleos(t)Ide Analogues, in Reducing the Incidence of HCC in Chronic Hepatitis B Patients With Intermediate to High Liver Cancer Risks

Qing XIe

Director of Department of Infectious Disease, Rui Jin Hospital

Hepatitis C

Hepatitis C, Chronic

Neoplasms, Glandular and Epithelial

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Flaviviridae Infections

Ribavirin

Peginterferon alfa-2a

Antimetabolites

100 naïve CHC patients concomitant with hepatocellular carcinoma without clinical evidence of HCC recurrence more than 3 months after curative treatments.

100 naïve CHC patients without malignancy

They received peginterferon alpha-2a (180 μg/week) and weight-based ribavirin 1000-1200 mg/day, with a 24-week follow-up period.

peginterferon alpha-2a and ribavirin

Wan-Long Chuang, MD

Combination therapy with pegylated interferon-alpha plus ribavirin has greatly improved the treatment efficacy and is the mainstream of treatment for chronic hepatitis C infection. The efficacy and safety of pegylated interferon-alpha plus ribavirin combination therapy and its impact on the outcome in chronic hepatitis C patients concomitant with hepatocellular carcinoma deserve to be elucidated.

The purposes of this study are:

1. To evaluate the efficacy and safety of pegylated interferon-alpha 2a plus ribavirin combination therapy in chronic hepatitis C patients concomitant with hepatocellular carcinoma.
2. To investigate the role of baseline and on-treatment factors on the response to pegylated interferon-alpha 2a plus ribavirin combination therapy in chronic hepatitis C patients concomitant with hepatocellular carcinoma.

A prospective, hospital-based study enrolling 100 chronic hepatitis C patients concomitant with hepatocellular carcinoma and other sex- and age-matched 100 chronic hepatitis C patients without malignancy will be conducted. The 100 chronic hepatitis C patients concomitant with hepatocellular carcinoma will receive pegylated interferon-alpha 2a plus ribavirin combination therapy at remission phase after oncological treatments and/or interventions. The other 100 chronic hepatitis C patients without malignancy receiving the same antiviral therapy will serve as controls. The primary outcome measurement is sustained virological response and safety, whilst the secondary measurement is rapid virological and early virological response.

Peginterferon Plus Ribavirin for Hepatitis C Patients Concomitant With Hepatocellular Carcinoma

The Response and Outcomes of Pegylated Interferon Plus Ribavirin Combination Therapy for Chronic Hepatitis C Patients Concomitant With Hepatocellular Carcinoma

Kaohsiung Medical University Chung-Ho Memorial Hospital

Wan-Long Chuang, MD.

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Myeloproliferative Disorders

Bone Marrow Diseases

Myeloid Leukemia

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Tin Fluorides

Mitogens

Tyrosine Kinase Inhibitors

Tyrosine

Subcutaneous peginterferon-α-2a (PEGASYS®) starting at 180µg weekly for one year

Stop tyrosine kinase inhibitor that was on and no active medication that might affect CML, for example any immune-modulatory agents, traditional herbs or medications, chemotherapeutic agents, growth factors, or colony stimulating factors is allowed during the trial period.

Subcutaneous peginterferon-α-2a (PEGASYS®) starting at 180µg weekly for one year.

Peginterferon-α-2a

Kian Meng Chang, FRCP(London)

To compare administration of peginterferon-α-2a for 1 year versus observation after stopping tyrosine kinase inhibitor (TKI) in chronic myeloid leukemia (CML) patients with deep MR ≥ 2 years.

Chronic myeloid leukemia (CML) is a chronic myeloproliferative neoplasm signified by the presence of Philadephia chromosome, which is the derivative of chromosome 22 after translocation between chromosome 9 and 22. The Philadephia chromosome will produce the mutated tyrosine kinase (BCR-ABL1), which will initiate the pathogenesis of the disease.

Imatinib is the first tyrosine kinase inhibitor (TKI), which has changed the treatment paradigm of CML since its approval from U.S. Food and Drug Administration in 2001 for the treatment of CML. It signifies a new era of oncological treatment using targeted therapy. Subsequent generation TKIs have been marketed as a more potent therapy for CML. Tyrosine kinase inhibitor is conventionally thought not able to cure CML and it has to be taken for life. It is able to induce a very deep molecular response (MR) in about 10% of CML patients as evidenced by persistent undetectable or ≤0.0032% (International Scale IS) BCR-ABL1 transcript in quantitative polymerase chain reaction (PCR) test on current molecular assays, which is labelled as MR4.5 or more. However these patients have to continue taking their TKIs as per recommendations from the European Leukaemia Net and this is the current practice in our institution and in Malaysia. Long term treatment is cumbersome, there is a concern of chronic side effects with long term tyrosine kinase inhibition and it is a financial burden on most countries' health budget as these drugs are very expensive.

Current available data showed that 40% of CML patients with prior stable MR4.5 for 2 years or more will be able to stay imatinib-free for at least 2 years. About 13% of patients without confirmed molecular relapse by the study criteria have low persistent BCR-ABL1 but remain imatinib-free for median follow-up of 22 months (range 6 - 35). A few patients with confirmed molecular relapse by study criteria remained drug free on follow-up. This postulates a component of immunity suppressing the leukemic clone.

Interferon is the standard treatment of CML before the era of TKI. As a single agent, it induces complete cytogenetic response (CCR) in about 20%, and non-sustainable deep MR in about 10% of patients in early chronic phase. These are much smaller figures compared to TKI. Imatinib at the dose of 400mg daily induces CCR in about 70% and deep MR in about 10% of patient in chronic phase after one year of treatment. However, interferon-responded patients may indeed retain the response once interferon was withdrawn via interferon-induced immunity towards the leukemic clone, which leads to longer drug free period compared to TKI. Hence, it is logical to postulate the use of interferon after TKI was stopped when patients have attained deep MR for more than two years will increase the percentage of patients remain TKI-free on follow-up. Unfortunately, there are not many studies concerning this matter. Carella et al described a case series of five patients with deep MR ranging from 12 to 41 months, were put on interferon with follow-up ranging from three to 16 months. Recently, there was a study from Japan, nine out of 12 analyzable patients including 3 patients with previous treatment of interferon, who stopped TKI, was put on interferon remained in deep MR after median follow-up of 23 months (6-27 months). In regards to peginterferon, there is a small studies by Hardan I et al describing 11 CML patients with various responses after imatinib (from complete cytogenetic response N=3, major molecular response N=6, deep MR N=2) were put on peginterferon-α-2a for nine months together with imatinib, then imatinib was stopped and continued with peginterferon-α-2a for another three months. It is difficult to draw any conclusion from this paper because of the small number of subjects, only two subjects have achieved deep MR (with unknown duration) before study entry, and peginterferon-α-2a was combined with imatinib for nine months which will cloud the true effect of peginterferon-α-2a after imatinib was stopped.

So far, there is no randomized study comparing interferon administered for fix duration after TKI was stopped versus observation to see whether the percentage and duration of CML patient who remains TKI-free can be increased and prolonged with interferon, respectively. It will be of interest to see how long the group which was given interferon remains TKI-free. If they remain TKI-free for a long duration, it not only suggests the interferon-induced immunity, but also suggests the interferon-induced immunity can be induced when only a very low level of leukemic cells present. Economical wise, TKI-free certainly give a big relief on the limited health budget of the on-growing CML population.

Malaysia Stop Tyrosine Kinase Inhibitor Trial

A Randomized Control Trial Comparing Peginterferon-α-2a Versus Observation After Stopping Tyrosine Kinase Inhibitor in Chronic Myeloid Leukemia With Deep Molecular Response for at Least Two Years

Relapse is defined as either i. Loss of MMR, which is a reading of \> 0.1% IS, which need to be confirmed by a second analysis point if no previous increasing trend of PCR result, or ii. Positivity of BCR-ABL1 transcripts in quantitative PCR, as confirmed by a second analysis point, indicating the increase (at least 1 log) in relation to the first analysis point at two successive assessments.

The number of patients who developed adverse side-effects of interferon vs observation arm.

The success rate of reattaining deep MR after restarting TKI in those patients who relapse.

Defined as time of relapse to the first time point, after restarting whatever treatment, patient has deep MR confirmed by second analysis point.

Assessed by questionnaire from INTERNATIONAL PROJECT ON QUALITY OF LIFE IN CHRONIC MYELOID LEUKEMIA.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Peginterferon α-2b as a Maintenance Therapy in Participants With Multiple Myeloma Who Responded to Induction Therapy (P01972-AM7)	NCT00732641	Multiple Myelom...	Peginterferon	18 Years - 85 Years	Merck Sharp & Dohme LLC
A Prospective Study to Evaluate Peginterferon in Reducing the Incidence of HCC in CHB Patients	NCT05671315	Chronic Hepatit... Intermediate to...	Peginterferon a... Nucleos(t)ide a...	18 Years - 60 Years	Ruijin Hospital
Peginterferon Plus Ribavirin for Hepatitis C Patients Concomitant With Hepatocellular Carcinoma	NCT00834860	Chronic Hepatit... Hepatocellular ...	peginterferon a...	18 Years -	Kaohsiung Medical University Chung-Ho Memorial Hospital
Malaysia Stop Tyrosine Kinase Inhibitor Trial	NCT02381379	Leukemia, Chron...	Peginterferon-α...	18 Years -	Ministry of Health, Malaysia

Spots Global Cancer Trial Database for peginterferon