Lenalidomide or Observation in Treating Patients With Asymptomatic High-Risk Smoldering Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01169337
First received: July 23, 2010
Last updated: July 18, 2014
Last verified: June 2014
  Purpose

This phase II/III trial studies how well lenalidomide works and compares it to observation in treating patients with asymptomatic high-risk 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.


Condition Intervention Phase
Light Chain Deposition Disease
Smoldering Multiple Myeloma
Drug: lenalidomide
Other: clinical observation
Other: laboratory biomarker analysis
Other: quality-of-life assessment
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase III Trial of Lenalidomide Versus Observation Alone in Patients With Asymptomatic High-Risk Smoldering Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Incidence of grade 3 or higher toxicities based on Cancer Therapy Evaluation Program-Adverse Event Reporting System expedited reporting (Phase II) [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]
  • PFS (Phase III) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    PFS in each of the arms will be estimated using the method of Kaplan and Meier. PFS between the two arms will be compared using a stratified log-rank test. Cox proportional hazards model will be used to assess PFS outcome in multiple regression analyses of established prognostic factors.


Secondary Outcome Measures:
  • Response rate (complete and partial response) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Calculated with a 95% confidence interval.

  • Duration of response [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.

  • Incidence of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
    Adverse events will be monitored on all patients and summarized by arm. The difference in rates of all grade 3 or higher toxicities will be evaluated for all randomized patients using the Fisher's Exact test.

  • Overall survival (OS) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan and Meier. OS between the two arms will be compared using stratified log-rank test. Cox proportional hazards model will be used to estimate the hazard rate between arms.


Other Outcome Measures:
  • Mean change of the FACT-FWB+PWB score [ Time Frame: Baseline to up to 24 months ] [ Designated as safety issue: No ]
    A two-sided t-test will be used.

  • Change in FACT-FWB+PWB mean scores between patients that experience disease progression (PD) and patients who do not experience PD [ Time Frame: Baseline to up to 48 months ] [ Designated as safety issue: No ]
    Assessed using mixed effects model.

  • Sensitivity for patients that did experience PD during the interval with respect to change in QOL in QOL status since last QOL assessment [ Time Frame: Up to 48 months ] [ Designated as safety issue: No ]
  • Reliability of PACT-FWB+PWB [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Descriptive statistics will be provided and Chronbach's alpha will be calculated to assess reliability.

  • Reliability of MMS [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Descriptive statistics will be provided and Chronbach's alpha will be calculated to assess reliability.

  • Differences in the MMS between the two arms [ Time Frame: At 24 months ] [ Designated as safety issue: No ]
  • Validity of FACT-PWB+FWB [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Patients will be segmented into clinical groups such as ECOG performance status 0-1 vs 2 that are expected to have significantly different scores and these relationships will be analyzed with 1-way multivariate analysis of variance (MANOVA). When MANOVA is significant then a univariate analysis of variance is done on each dependent variable.

  • Validity of MMS [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Patients will be segmented into clinical groups such as ECOG performance status 0-1 vs 2 that are expected to have significantly different scores and these relationships will be analyzed with 1-way MANOVA. When MANOVA is significant then a univariate analysis of variance is done on each dependent variable.

  • Change in gene expression profiling [ Time Frame: Baseline to up to 10 years ] [ Designated as safety issue: No ]
    Exploratory analyses will be performed to examine the underlying distributions using box plots, density plots, scatter plots, etc. Differential expression analysis of the two groups (baseline vs. off-study) will be performed.

  • Change in immune expression [ Time Frame: Baseline to up to 10 years ] [ Designated as safety issue: No ]
    Changes in immune expression will be evaluated only by descriptive statistics for hypothesis generation.

  • Presence of focal lesions on baseline MRI [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The data about the presence of focal lesions on baseline MRI studies will be analyzed and correlated with clinical outcome. The difference in response rates will be analyzed using the Fisher's exact test assuming a target overall response rate of 25% and 5% level of significance.

  • Prevalence of cytogenetic abnormalities [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    There will be 80% power with the logrank test to detect a hazard ratio comparing high-risk vs. standard-risk cytogenetic groups.


Estimated Enrollment: 380
Study Start Date: October 2010
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (lenalidomide)
Patients receive lenalidomide PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Active Comparator: Arm B (observation)
Patients undergo observation until progression to symptomatic myeloma.
Other: clinical observation
Undergo observation
Other Name: observation
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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/mm^3
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • 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
  • Human immunodeficiency virus (HIV) infection is not excluded; HIV+ patients must meet the following criteria:

    • Cluster of differentiation (CD)4 cell count >= 350/mm^3
    • No history of acquired immune deficiency syndrome (AIDS)-related illness
    • Not currently prescribed zidovudine or stavudine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01169337

  Show 340 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Sagar Lonial ECOG-ACRIN Cancer Research Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01169337     History of Changes
Other Study ID Numbers: NCI-2011-02057, NCI-2011-02057, ECOG-E3A06, CDR0000682012, E3A06, E3A06, U10CA180820, U10CA021115
Study First Received: July 23, 2010
Last Updated: July 18, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Lenalidomide
Thalidomide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014