Randomized Phase III Trial of Lenalidomide Versus Observation Alone in Patients With Asymptomatic High-Risk Smoldering Multiple Myeloma
Overview
- Phase
- Phase 3
- Status
- Active, not recruiting
- Enrollment
- 226
- Locations
- 1,214
- Primary Endpoint
- 2-year Progression-free Survival (PFS) Rate (Phase III Primary Endpoint)
Overview
Brief Summary
This randomized phase II/III trial studies how well lenalidomide works and compares it to observation in treating patients with asymptomatic high-risk asymptomatic (smoldering) multiple myeloma. Biological therapies such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Sometimes the cancer may not need treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether lenalidomide is effective in treating patients with high-risk smoldering multiple myeloma than observation alone.
Detailed Description
PRIMARY OBJECTIVES:
I. To study the risk of grade 3 adverse events that effect vital organ function (such as cardiac, hepatic or thromboembolic) or any grade 4 or higher non-hematologic adverse events among patients receiving lenalidomide as treatment for high-risk asymptomatic, smoldering multiple myeloma. (Phase II) II. To compare progression free survival where failure is defined as death or the development of symptomatic myeloma indicating treatment between patients receiving lenalidomide versus observation alone in high-risk asymptomatic, smoldering multiple myeloma. (Phase III)
SECONDARY OBJECTIVES:
I. To assess the response to therapy of patients treated with lenalidomide as treatment for asymptomatic, smoldering multiple myeloma. (Phase II) II. To determine and compare the response rate, time to progression, 1-year progression-free survival probability, and overall survival between patients randomized to receive lenalidomide or observation in the setting of asymptomatic myeloma. (Phase III) III. To estimate the incidence of adverse events in patients receiving lenalidomide therapy for early-stage multiple myeloma. (Phase III)
CORRELATIVE OBJECTIVES:
I. To describe the cohort in terms of gene expression profiling (GEP) and cytogenetic risk classification and evaluate baseline immune and magnetic resonance imaging (MRI) parameters. (Phase II) II. To evaluate the impact of therapy within GEP-defined risk groups and GEP as a prognostic marker. (Phase III) III. To study the effects of lenalidomide on laboratory markers of immune function. (Phase III) IV. To study the prognostic value of MRI-detected asymptomatic bone disease on clinical outcome. (Phase III) V. To evaluate the prognostic effect of baseline high-risk cytogenetic abnormalities on clinical outcome. (Phase III)
QUALITY OF LIFE ASSESSMENT OBJECTIVES:
I. To compare quality of life (QOL) change between treatment and observation arms based on the functional (FWB) and physical (PWB) well-being components of the Functional Assessment of Cancer Therapy (FACT)-General (G) patient-reported outcome (PRO) measure from registration (prior to initiation of treatment) up to cycle 24.
II. To examine the impact of differential treatment response (PFS), if observed, on QOL based on the FACT FWB+PWB up to cycle 48.
III. To obtain prospective data on myeloma specific QOL attributes, utilizing and evaluating the Multiple Myeloma Subscale (MMS).
OUTLINE:
PHASE II: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PHASE III: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients undergo observation until progression to symptomatic myeloma.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then every 12 months for 5 years.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients must be diagnosed with asymptomatic high-risk smoldering multiple myeloma (SMM) within the past 60 months, as confirmed by both of the following:
- •Bone marrow plasmacytosis with \>= 10% plasma cells or sheets of plasma cells at any time before initiating study treatment, including a marrow which must be obtained by bone marrow aspiration and/or biopsy within 4 weeks prior to randomization
- •Abnormal serum free light chain ratio (\< 0.26 or \> 1.65) by serum free light chain (FLC) assay; FLC assay must be performed within 28 days of randomization
- •Patients must have measurable levels of monoclonal protein (M-protein): \>= 1g/dL on serum protein electrophoresis or \>= 200 mg of monoclonal protein on a 24 hour urine protein electrophoresis which must be obtained within 4 weeks prior to randomization
- •Patients must have no lytic lesions on skeletal surveys and no hypercalcemia (i.e., \>= 11 mg/dL)
- •Hemoglobin \>= 11 g/dL within four weeks prior to randomization
- •Platelet count \>= 100,000/mm\^3 within four weeks prior to randomization
- •Absolute neutrophil count (ANC) \>= 1,500/mm\^3 within four weeks prior to randomization
- •Calculated creatinine clearance \>= 30 mL/min within four weeks prior to randomization
- •Bilirubin =\< 1.5 mg/dL within four weeks prior to randomization
Exclusion Criteria
- Not provided
Arms & Interventions
Arm A (lenalidomide)
Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Lenalidomide (Drug)
Arm A (lenalidomide)
Patients receive lenalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: Quality-of-Life Assessment (Other)
Arm B (observation)
Patients undergo observation until progression to symptomatic myeloma.
Intervention: Clinical Observation (Other)
Arm B (observation)
Patients undergo observation until progression to symptomatic myeloma.
Intervention: Quality-of-Life Assessment (Other)
Outcomes
Primary Outcomes
2-year Progression-free Survival (PFS) Rate (Phase III Primary Endpoint)
Time Frame: Assessed every 3 months for 2 years
PFS is defined as time from randomization to progression or death, whichever occurs first. Patients are considered to have progression if both of the following criteria are met. Kaplan-Meier method was used to estimate 2-year PFS rate. 1. Any of the following: * Increase in serum M-protein to ≥ 25% above the lowest response level with an absolute increase of at least 0.5g/dl to qualify as "progression" * Increase in urine M-protein to ≥ 25% above the lowest response level for 24-hour excretion with an absolute increase of at least 200mg/24 hours of urine M-protein to qualify as "progression" * Increase in bone marrow plasma cell percentage to ≥ 25% from lowest response value (the absolute % increase must be ≥ 10%) 2. Any of the following felt related to the underlying clonal plasma cell proliferative disorder: * Hypercalcemia (\> 11 mg/dL) * Decrease in hemoglobin of ≥ 2 gms/dL * Serum creatinine level ≥ 2mg/dL * Development of myeloma bone lesions or soft tissue plasmacytoma
Proportion of Patients With Grade 3 Adverse Events That Effect Vital Organ Function or Any Grade 4 or Higher Non-hematologic Adverse Events (Phase II Primary Endpoint)
Time Frame: Assessed every 4 weeks while on treatment up to 24 weeks
Proportion of patients with grade 3 adverse events that effect vital organ function (such as cardiac, hepatic or thromboembolic) or any grade 4 or higher non-hematologic adverse events
Secondary Outcomes
- Proportion of Participants With Response (Phase III Secondary Endpoint)(Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, then annually for years 6-10)
- 2-year Overall Survival (OS) Rate (Phase III Secondary Endpoint)(Assessed every 3 months for 2 years)
- Proportion of Participants With Response (Phase II Secondary Endpoint)(Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, then annually for years 6-10)
- 1-year Progression-free Survival (PFS) Rate (Phase III Secondary Endpoint)(Assessed every 3 months for one year)
- 2-year Progression-free Rate (Phase III Secondary Endpoint)(Assessed every 3 months for 2 years)