We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT01169337
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01169337
Recruitment Status : Active, not recruiting
First Posted : July 26, 2010
Results First Posted : May 18, 2021
Last Update Posted : May 3, 2023
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Light Chain Deposition Disease Smoldering Plasma Cell Myeloma Other: Clinical Observation Drug: Lenalidomide Other: Quality-of-Life Assessment Phase 3

Show Show detailed description
Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 226 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Actual Study Start Date : January 24, 2011
Actual Primary Completion Date : January 25, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: 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.
 Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid

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: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. Proportion of Participants With Response (Phase II Secondary Endpoint) [ Time Frame: 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 ]

    Response is defined as complete response (CR), very good partial response (VGPR) or partial response (PR).

    CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <=5% plasma cells in bone marrow VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-component plus urine M-component < 100 mg per 24 hours

    PR:

    • ≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hours
    • If followed by free light chain (FLC) only, a ≥ 50% decrease in the difference between involved and uninvolved FLC levels
    • If unmeasurable disease by serum M-protein, urine M-protein, and serum FLC at baseline, a ≥50% reduction in plasma cells provided baseline bone marrow percentage was ≥ 30%
    • If present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas

  2. Proportion of Participants With Response (Phase III Secondary Endpoint) [ Time Frame: 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 ]

    Response is defined as complete response (CR), very good partial response (VGPR) or partial response (PR).

    CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <=5% plasma cells in bone marrow VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-component plus urine M-component < 100 mg per 24 hours

    PR:

    • ≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hours
    • If followed by free light chain (FLC) only, a ≥ 50% decrease in the difference between involved and uninvolved FLC levels
    • If unmeasurable disease by serum M-protein, urine M-protein, and serum FLC at baseline, a ≥50% reduction in plasma cells provided baseline bone marrow percentage was ≥ 30%
    • If present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas

  3. 1-year Progression-free Survival (PFS) Rate (Phase III Secondary Endpoint) [ Time Frame: Assessed every 3 months for one year ]

    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 1-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

  4. 2-year Progression-free Rate (Phase III Secondary Endpoint) [ Time Frame: Assessed every 3 months for 2 years ]

    TTP is defined as the time from randomization to progression. Patients are considered to have progression if both of the following criteria are met. Kaplan-Meier method was used to estimate 2-year progression-free 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 one or more 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

  5. 2-year Overall Survival (OS) Rate (Phase III Secondary Endpoint) [ Time Frame: Assessed every 3 months for 2 years ]
    Overall survival is defined as the time from randomization to death or date last known alive among all randomized patients in the phase III part of the study. Kaplan-Meier method was used to estimate the 2-year OS rate.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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 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
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) and serum glutamic oxaloacetic transaminase (SGPT) (aspartate aminotransferase [AST]) =< 2.5 times upper limit of normal within four weeks prior to randomization
  • 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/mm^3
    • No history of acquired immune deficiency syndrome (AIDS)-related illness
    • Not currently prescribed zidovudine or stavudine
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01169337


Locations
Show Show 613 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Sagar Lonial ECOG-ACRIN Cancer Research Group
  Study Documents (Full-Text)

Documents provided by National Cancer Institute (NCI):
Study Protocol and Statistical Analysis Plan  [PDF] September 26, 2019

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01169337    
Other Study ID Numbers: NCI-2011-02057
NCI-2011-02057 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ECOG-E3A06
CDR0000682012
E3A06 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
E3A06 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
U10CA021115 ( U.S. NIH Grant/Contract )
U24CA196172 ( U.S. NIH Grant/Contract )
First Posted: July 26, 2010    Key Record Dates
Results First Posted: May 18, 2021
Last Update Posted: May 3, 2023
Last Verified: November 2022
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Myeloma
Neoplasms, Plasma Cell
Smoldering Multiple Myeloma
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
Precancerous Conditions
Hypergammaglobulinemia
Lenalidomide
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents