E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Asymptomatic High-Risk Smoldering Multiple Myeloma |
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E.1.1.1 | Medical condition in easily understood language |
High-risk asymptomatic myeloma, a type of blood cell cancer that has not yet damaged body tissue and organs to the point where symptoms are noticeable. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
SECONDARY -To determine & compare the response rate,time to progression,1-year PFS probability & overall survival between patients randomized to receive lenalidomide or observation in the setting of asymptomatic myeloma. -To estimate the incidence of AE’s in patients receiving lenalidomide therapy for early-stage MM.
CORRELATIVE -To evaluate the impact of therapy within GEP-defined risk groups and GEP as a prognostic marker. -To study the effects of lenalidomide on laboratory markers of immune function. -To study the prognostic value of MRI detected asymptomatic bone disease on clinical outcome. -To evaluate the prognostic effect of baseline high-risk cytogenetic abnormalities on clinical outcome.
QUALITY OF LIFE ASSESSMENT
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age ≥ 18 years.
- Patients must be diagnosed with asymptomatic high-risk smoldering multiple myeloma (SMM) within the past 60 months, as confirmed by both of the following: 1) Bone marrow plasmacytosis or 2) Abnormal serum free light chain ratio
- 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
- Patients must have no lytic lesions on skeletal surveys and no hypercalcemia (i.e., > 11 mg/dL).
- The following laboratory levels must be obtained within four weeks prior to randomization: Hemoglobin ≥ 11 g/dL / Platelet count ≥ 100,000 cells/mm3 / Absolute neutrophil count ≥ 1500 cells/mm3 / Calculated creatinine clearance ≥ 30 mL/min / Bilirubin ≤ 1.5 mg/dL / SGPT (ALT) and SGOT (AST) ≤ 2.5 times the upper limit of normal.
- 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.
- ECOG performance status 0, 1, or 2.
- 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 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.
- 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.
- HIV infection is not excluded. HIV+ patients must meet the following criteria: * CD4 cell count > 350/mm3 * No history of AIDS-related illness * Not currently prescribed zidvoudine or stavudine
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E.4 | Principal exclusion criteria |
- 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.
- 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.
- 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 should not have New York Heart Association classification III or IV heart failure.
- Patients should not be felt to have an immediate need for chemotherapy.
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E.5 End points |
E.5.1 | Primary end point(s) |
The most clinically relevant endpoint for this high-risk SMM population is progression free survival (PFS) as defined by the ASH FDA consensus panel, where failure is defined as death or the appearance of symptomatic myeloma indicating treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
This design incorporates 5 interim analyses and one final analysis for the PFS comparison. The final analysis will occur at full information (124 patients progressed/died). |
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E.5.2 | Secondary end point(s) |
Secondary endpoints for this study include response rate and duration of response among responders.
Overall Survival (OS) will also be assessed. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
OS will be evaluated at month 90/ year 7.5 when there is adequate power.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Bone Marrow&Peripheral Blood for Laboratory Studies:
Pharmacogenetic: The goal of the planned lab correlative studies is to better understand the impact of certain cytogenetic characteristics with differential risk of progression given respective treatments.Specifically,evaluation of the impact of the high-risk cytogenetics which includes patients with t(4;14)(p16;q32), t(14;16) (q32;q23)&those having 17p deletions,all of which they hypothesize will adversely affect the risk of progression. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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For this protocol, all patients, including those who discontinue protocol therapy early, will be followed for response until progression and for survival for 10 years from the date of randomization. All patients must also be followed through completion of all protocol therapy, and until PD, even if they initiate non-protocol therapy. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 13 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 13 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |