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

Study Overview
=================
Brief Summary
-----------------
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).

Official Title
-----------------
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)

Conditions
-----------------
Multiple Myeloma

Intervention / Treatment
-----------------
* Drug: Peginterferon


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Must demonstrate willingness to participate in the study and to adhere to dose and visit schedules Must be ≤85 years of age of either sex, and any race Must have stage II or III multiple myeloma with a histological confirmation consistent with the diagnosis of multiple myeloma (by biopsy of an osteolytic or soft tissue tumour composed of plasma cells or bone marrow aspirate and/or biopsy demonstrating ≥ 10% plasmacytosis). The histological confirmation should have been obtained prior to the induction chemotherapy or bone marrow transplant chemotherapy May not have received prior interferon for the treatment of multiple myeloma Must confirm that he/she is practicing adequate contraception If a female volunteer of childbearing potential, must have a negative serum pregnancy test at Screening/Visit 1 -Must be free of any clinically relevant disease (other than multiple myeloma) that would, in the principal investigator's and/or sponsor's opinion, interfere with the conduct of the study or study evaluations Must be able to adhere to the dosing and visit schedules Clinical laboratory tests (complete blood chemistry [CBC], blood chemistries, urinalysis) must be consistent with adequate hepatic and renal function, defined as <2 times upper limit of any laboratory normal (ULN) and adequate hematological functions defined as platelets > 50,000/mm^3, Hemoglobin ≥9.0 g/dL, white blood count (WBC) count ≥2000/mm^3 -Must have a complete, partial or minimal response after either one induction chemotherapy regimen or one myelosuppressive chemotherapeutic treatment followed by peripheral blood stem cell infusion as a first line treatment. Any type of pre-transplant chemotherapy and conditioning regimen is allowed -Performance Status Karnofsky score of ≥60% at time of randomization Exclusion Criteria: Is a female who is pregnant, or intends to become pregnant during the study Is nursing, or intends to be nursing during the study Has used any investigational product within 30 days prior to enrollment Have any of the following clinical conditions: Pre existing psychiatric condition, especially depression, or a history of severe psychiatric disorder, such as major psychoses, suicidal ideation and/or suicidal attempt. Subjects with a history of mild depression may be considered for entry into the protocol provided that a pre-treatment assessment of the subject's mental status indicates that the subject is clinically stable and that there is ongoing evaluation of the patient's mental status during the study Central Nervous System (CNS) trauma or active seizure disorders requiring medication Significant cardiovascular dysfunction within the previous 6 months before the study starts (eg, angina, congestive heart failure, recent myocardial infarction, severe hypertension or significant arrhythmia) or patient with multigated acquisition (MUGA) or echocardiogram < 40%; History of prior malignant disease within the previous 5 years before the study starts, except for surgically cured squamous cell or basal cell skin carcinoma or Stage I cervical carcinoma or cervical carcinoma in situ; Known severe coagulation disorders, thrombophlebitis or pulmonary embolism or decompensate liver disease; Uncontrolled diabetes mellitus or thyroid dysfunction (not responsive to therapy); Severe chronic pulmonary disease (eg, chronic obstructive pulmonary disease); Has active and/or uncontrolled infection Is in a situation or condition that, in the opinion of the investigator, may interfere with optimal participation in the study Is participating in any other clinical study Is on the staff, affiliated with, or a family member of the staff personnel directly involved with this study Is allergic to or has sensitivity to the study drug or its excipients

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Peginterferon α-2b<br>Peginterferon α-2b 35 μg, weekly, subcutaneous (SC), until disease progression or relapse, or for up to a maximum of 5 years. | Drug: Peginterferon<br>* Peginterferon α-2b 35 μg, weekly, subcutaneous (SC), until disease progression or relapse, or for up to a maximum of 5 years.<br>|
| No Intervention: No Treatment<br>Participants will be observed and will receive no treatment. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Days With Progression Free Survival (PFS) | 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. | Baseline and up to 5 years (or to the date of the first documented tumor progression or relapse) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Days of Overall Survival (OS) | 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. | Baseline and up to 5 years (or to the date of the first documented tumor progression or relapse) | 
| Number of Participants With Complete Response (CR) to Treatment | 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. | Month 9 & Month 18 | 
| Number of Participants With Partial Response (PR) to Treatment | 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. | Month 9 & Month 18 | 
| Number of Participants With Minimal Response (MR) to Treatment | 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. | Month 9 & Month 18 | 
| Number of Participants With Progressive Disease(PD) or Relapse From CR | 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. | Month 9 & Month 18 | 
| Quality of Life | 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). | Screening and Last Observation (up to 5 years) |