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Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started

Description

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.

Official Title

Randomized Phase III Trial of Lenalidomide Versus Observation Alone in Patients With Asymptomatic High-Risk Smoldering Multiple Myeloma

Details

PRIMARY OBJECTIVES:

  1. 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:

  1. 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)

TERTIARY OBJECTIVES:

  1. 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)

QUATERNARY OBJECTIVES:

  1. 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. Courses 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. Courses 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.

Keywords

Light Chain Deposition Disease Smoldering Plasma Cell Myeloma Multiple Myeloma Neoplasms, Plasma Cell Lenalidomide Thalidomide

Eligibility

For people ages 18 years and up

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
  • Platelet count >= 100,000/mm3

  • Absolute neutrophil count (ANC) >= 1,500/mm3

  • Calculated creatinine clearance >= 30 mL/min
  • Bilirubin =< 1.5 mg/dL
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) and serum glutamic oxaloacetic transaminase (SGPT) (aspartate aminotransferase [AST]) =<2.5 times upper limit of normal
  • No prior or concurrent systemic or radiation therapy for the treatment of myeloma
  • Concurrent use of bisphosphonates is not permitted; however, prior bisphosphonates or once-a-year intravenous bisphosphonate given for the treatment of osteoporosis is permitted
  • Prior or concurrent use of erythropoietin is disallowed
  • Prior glucocorticosteroid therapy for the treatment of multiple myeloma is not permitted
  • Prior systemic glucocorticosteroid use for the treatment of non-malignant disorders is permitted; concurrent use after registration on the study should be restricted to the equivalent of prednisone 10 mg per day
  • Prior or concurrent topical or localized glucocorticosteroid therapy to treat non-malignant comorbid disorders is permitted
  • Patients must not have active, uncontrolled seizure disorder; patients must have had no seizures in the last 6 months
  • Patients must not have uncontrolled intercurrent illness including uncontrolled hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled cardiac arrhythmia, uncontrolled psychiatric illness or social situation that would limit compliance with the study, or a prior history of Stevens Johnson syndrome
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
  • Patients must not have baseline bone lesions or plasmacytomas
  • Patients with monoclonal gammopathy of undetermined significance are not eligible
  • Patients must not have grade 2 or higher peripheral neuropathy
  • Patients must not have active, uncontrolled infection
  • Patients may have a history of current or previous deep vein thrombosis or pulmonary embolism but are required to take some form of anti-coagulation as prophylaxis if they are not currently on full-dose anticoagulation
  • Patients should not have New York Heart Association classification III or IV heart failure
  • Patients with a history of prior malignancy are eligible provided they were treated with curative intent and have been free of disease for the time period considered appropriate for cure of the specific cancer; for most diseases this time frame is 5 years
  • Patients should not be felt to have an immediate need for chemotherapy
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting cycle 1 of lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; a FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2)has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure
  • Human immunodeficiency virus (HIV) infection is not excluded; HIV+ patients must meet the following criteria:
  • Cluster of differentiation (CD)4 cell count >= 350/mm3

  • No history of acquired immune deficiency syndrome (AIDS)-related illness
  • Not currently prescribed zidovudine or stavudine

Locations

  • California Pacific Medical Center-Pacific Campus
    San Francisco, California, 94115, United States
  • UCSF Medical Center-Mount Zion
    San Francisco, California, 94115, United States
  • UCSF Medical Center-Parnassus
    San Francisco, California, 94143, United States
  • Alta Bates Summit Medical Center-Herrick Campus
    Berkeley, California, 94704, United States
  • Mills-Peninsula Medical Center
    Burlingame, California, 94010, United States
  • Sutter Cancer Research Consortium
    Novato, California, 94945, United States
  • Palo Alto Medical Foundation Health Care
    Palo Alto, California, 94301, United States
  • Sutter Solano Medical Center/Cancer Center
    Vallejo, California, 94589, United States
  • Palo Alto Medical Foundation-Camino Division
    Mountain View, California, 94040, United States
  • Palo Alto Medical Foundation-Gynecologic Oncology
    Mountain View, California, 94040, United States
  • Palo Alto Medical Foundation-Sunnyvale
    Sunnyvale, California, 94086, United States
  • Sutter Pacific Medical Foundation
    Santa Rosa, California, 95403, United States
  • Palo Alto Medical Foundation-Santa Cruz
    Santa Cruz, California, 95065, United States
  • Sutter Medical Center Sacramento
    Sacramento, California, 95816, United States
  • Memorial Medical Center
    Modesto, California, 95355, United States
  • Sutter Auburn Faith Hospital
    Auburn, California, 95602, United States
  • Carson Tahoe Regional Medical Center
    Carson City, Nevada, 89703, United States
  • Reno Oncology Consultants
    Reno, Nevada, 89519, United States
  • Radiation Oncology Associates
    Reno, Nevada, 89509, United States
  • Renown Regional Medical Center
    Reno, Nevada, 89502, United States
  • Alpine Hematology-Oncology
    Reno, Nevada, 89503, United States
  • Saint Mary's Regional Medical Center
    Reno, Nevada, 89503, United States
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    Burbank, California, 91505, United States
  • Saint Jude Medical Center
    Fullerton, California, 92835, United States
  • UC Irvine Health/Chao Family Comprehensive Cancer Center
    Orange, California, 92868, United States
  • Comprehensive Cancer Centers of Nevada-Summerlin
    Las Vegas, Nevada, 89144, United States
  • Summerlin Hospital Medical Center
    Las Vegas, Nevada, 89144, United States
  • HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
    Las Vegas, Nevada, 89149, United States
  • Ann M Wierman MD LTD
    Las Vegas, Nevada, 89128, United States
  • Cancer and Blood Specialists-Tenaya
    Las Vegas, Nevada, 89128, United States
  • Comprehensive Cancer Centers of Nevada - Northwest
    Las Vegas, Nevada, 89128, United States
  • HealthCare Partners Medical Group Oncology/Hematology-Tenaya
    Las Vegas, Nevada, 89128, United States
  • Las Vegas Cancer Center-Medical Center
    Las Vegas, Nevada, 89148-2405, United States
  • 21st Century Oncology - Fort Apache
    Las Vegas, Nevada, 89148, United States
  • Comprehensive Cancer Centers of Nevada
    Las Vegas, Nevada, 89148, United States
  • Nevada Cancer Specialists-Fort Apache
    Las Vegas, Nevada, 89148, United States
  • HealthCare Partners Medical Group Oncology/Hematology-San Martin
    Las Vegas, Nevada, 89113, United States
  • University Medical Center of Southern Nevada
    Las Vegas, Nevada, 89102, United States
  • Cancer and Blood Specialists-Shadow
    Las Vegas, Nevada, 89106, United States
  • Nevada Cancer Research Foundation CCOP
    Las Vegas, Nevada, 89106, United States
  • Radiation Oncology Centers of Nevada Central
    Las Vegas, Nevada, 89106, United States
  • 21st Century Oncology - Vegas Tenaya
    Las Vegas, Nevada, 89182, United States
  • 21st Century Oncology
    Las Vegas, Nevada, 89109, United States
  • HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
    Las Vegas, Nevada, 89109, United States
  • Comprehensive Cancer Centers of Nevada - Central Valley
    Las Vegas, Nevada, 89169, United States
  • University Cancer Center
    Las Vegas, Nevada, 89169, United States
  • Radiation Oncology Centers of Nevada Southeast
    Las Vegas, Nevada, 89119, United States
  • Cancer and Blood Specialists-Henderson
    Henderson, Nevada, 89052, United States
  • Comprehensive Cancer Centers of Nevada - Henderson
    Henderson, Nevada, 89052, United States
  • Las Vegas Cancer Center-Henderson
    Henderson, Nevada, 89052, United States
  • Cancer Therapy and Integrative Medicine
    Las Vegas, Nevada, 89121, United States
  • 21st Century Oncology - Henderson
    Henderson, Nevada, 89074, United States
  • Comprehensive Cancer Centers of Nevada-Southeast Henderson
    Henderson, Nevada, 89074, United States
  • Eisenhower Medical Center
    Rancho Mirage, California, 92270, United States

Details

Status
in progress, not accepting new patients
Start Date
Sponsor
National Cancer Institute (NCI)
ID
NCT01169337
Phase
Phase 3
Lead Scientist
Study Type
Interventional
Last Updated
October 16, 2017