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)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00732641

Enrollment

244

Registered

2008-08-12

Start date

2000-12-31

Completion date

2010-11-30

Last updated

2017-04-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Multiple Myeloma

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).

Interventions

DRUGPeginterferon

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 85 Years

Healthy volunteers

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

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Number of Participants With Complete Response (CR) to Treatment	Month 9 & Month 18	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.
Number of Participants With Partial Response (PR) to Treatment	Month 9 & Month 18	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.
Number of Days of Overall Survival (OS)	Baseline and up to 5 years (or 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.
Number of Participants With Progressive Disease(PD) or Relapse From CR	Month 9 & Month 18	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.
Quality of Life	Screening and Last Observation (up to 5 years)	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).
Number of Participants With Minimal Response (MR) to Treatment	Month 9 & Month 18	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.

Participant flow

Participants by arm

Arm	Count
Peginterferon α-2b Peginterferon α-2b 35 μg, weekly, subcutaneous (SC), until disease progression or relapse, or for up to a maximum of 5 years.	122
No Treatment Participants were observed and received no treatment	121
Total	243

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Other	18	5
Overall Study	Physician Decision	6	0
Overall Study	Relapse or Progressive Disease	65	101
Overall Study	Serious Adverse Events	12	3
Overall Study	Unable to Complete	1	1
Overall Study	Withdrawal by Subject	4	2

Baseline characteristics

Characteristic	Peginterferon α-2b	No Treatment	Total
Age, Continuous	61.0 years STANDARD_DEVIATION 8.5	62.3 years STANDARD_DEVIATION 8.6	61.7 years STANDARD_DEVIATION 8.6
Region of Enrollment Italy	123 participants	121 participants	244 participants
Sex: Female, Male Female	53 Participants	60 Participants	113 Participants
Sex: Female, Male Male	69 Participants	61 Participants	130 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	94 / 123	63 / 121
serious Total, serious adverse events	27 / 123	21 / 121

Outcome results

Primary

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.

Time frame: Baseline and up to 5 years (or to the date of the first documented tumor progression or relapse)