Smoldering Multiple Myeloma, Smoldering Myeloma
Conditions
Keywords
Smoldering myeloma, Smoldering Multiple Myeloma
Brief summary
This research study is aimed to determine the proportion of high risk smoldering multiple myeloma patients who are progression free at 2 years after receiving elotuzumab, lenalidomide and dexamethasone combination therapy.
Detailed description
This research study is a Phase II clinical trial, which tests the effectiveness of the investigational drugs elotuzumab, lenalidomide and dexamethasone in smoldering multiple myeloma. Recent research studies have shown that early treatment of smoldering multiple myeloma may delay or prevent the progression to active multiple myeloma. The purpose of this research study is to learn whether the combination of elotuzumab, lenalidomide and dexamethasone works in treating smoldering multiple myeloma.
Interventions
DRUGElotuzumab
10 mg/kg IV; Days 1, 8,15, 22 Cycles 1-2 10 mg/kg IV; Days 1 & 15 Cycles 3-8
DRUGLenalidomide
25 mg Oral; Days 1-21 days Cycles 1-24
DRUGDexamethasone
40 mg Oral; Days 1, 8, 15, 22 Cycles 1-2 40 mg Oral; Days 1, 8, 15 Cycles 3-8
Sponsors
Bristol-Myers Squibb
Celgene
Blood Cancer Research Partnership
Multiple Myeloma Research Consortium
The Leukemia and Lymphoma Society
Dana-Farber Cancer Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Must have smoldering myeloma with high risk markers based on the Mayo OR the Spanish criteria as described below * \>10% plasma cells in the bone marrow and any one or more of the following: * Serum M protein of 3 g/dL or greater * IgA SMM * Immunoparesis with reduction of two uninvolved immunoglobulin isotypes * Serum involved/uninvolved free light chain ratio ≥8 (but less than 100) * Progressive increase in M protein level (Evolving type of SMM)† * Bone marrow clonal plasma cells 50-60% * Abnormal plasma cell immunophenotype (≥95% of bone marrow plasma cells are clonal) and reduction of one or more uninvolved immunoglobulin isotypes * t (4;14) or del 17p or 1q gain * Increased circulating plasma cells * MRI with diffuse abnormalities or 1 focal lesion * PET-CT with focal lesion with increased uptake without underlying osteolytic bone destruction † Increase in serum monoclonal protein by ≥25% on two successive evaluations within a 6 month period * No evidence of CRAB (see below for details) criteria or new criteria of active multiple myeloma which including the following: * Increased calcium levels (corrected serum calcium \>0.25 mmol/dL above the upper limit of normal or \>.275 mmol/dL) * Renal insufficiency (attributable to myeloma) * Anemia (Hb 2g/dL below the lower limit of normal or \<10g/dL) * Bone lesions (lytic lesions or generalized osteoporosis with compression fractures) * No evidence of the following new criteria for active MM including the following: Bone marrow plasma cells ≥ 60%, Serum involved/uninvolved FLC ratio ≥100, and MRI with more than one focal lesion * Participants with CRAB criteria that are attributable to conditions other than the disease under study may be eligible * ECOG Performance Status (PS) 0, 1, or 2 (Appendix A) * The following laboratory values obtained ≤ 14 days prior to registration: * ANC ≥1000/µL * PLT ≥ 50,000/µL * Total bilirubin ≤ 2.0 mg/dL (If total is elevated check direct and if normal patient is eligible.) * AST ≤ 3 x institutional upper limit of normal (ULN) * ALT ≤ 3 x institutional upper limit of normal (ULN) * Estimated creatinine clearance ≥ 60mL/min or a creatinine ≤ 2.2 mg/dL * Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care * Females of childbearing potential\* must have a negative serum or urine pregnancy test * Men must agree to use a latex condom during sexual contact with a female of childbearing potential even if they have had a successful vasectomy * Ability to understand and the willingness to sign a written informed consent. *
Exclusion criteria
* Symptomatic Multiple Myeloma or any evidence of CRAB criteria including the new criteria for overt myeloma. Any prior therapy for active Myeloma should also be excluded. Prior therapy for smoldering myeloma is not an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Patients Who Are Progression Free at 2 Years | 2 Years | Percent of patients who are alive and without documented progression after at least 2-years of follow-up. All patients who receive study treatment are assessed including those who have died or lost to follow-up prior to 2-years. Progression was defined as an increase in SPEP \[25% and an absolute increase of 0.5g/d\] or UPEP \[25% and an absolute increase of 200mg/24hours\] on 2 successive evaluations as determined by the IMWG response criteria or documented progression by the FreeLite progressive disease criteria in the absence of serum or urine involvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Percent | 2 Years from start of treatment | Percent of patients with objective response defined as partial response or better based on the International Myeloma Working Group Response (IMWG) criteria |
| Time to Progression | From start of treatment up to +/- 60 months | Time from initiation of therapy to progression defined by the IMWG criteria. |
| Overall Survival | From start of treatment up to +/- 60 months | Time from initiation of therapy to death |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Elo / Len / Dex •Drug: Elotuzumab 10 mg/kg IV; Days 1, 8,15, 22 Cycles 1-2 10 mg/kg IV; Days 1 & 15 Cycles 3-8
Other Name: HuLuc63
•Drug: Lenalidomide 25 mg Oral; Days 1-21 days Cycles 1-24
Other Name: REVLIMID
•Drug: Dexamethasone 40 mg Oral; Days 1, 8, 15, 22 Cycles 1-2 40 mg Oral; Days 1, 8, 15 Cycles 3-8
Other Name: Decadron
Elotuzumab: 10 mg/kg IV; Days 1, 8,15, 22 Cycles 1-2 10 mg/kg IV; Days 1 & 15 Cycles 3-8
Lenalidomide: 25 mg Oral; Days 1-21 days Cycles 1-24
Dexamethasone: 40 mg Oral; Days 1, 8, 15, 22 Cycles 1-2 40 mg Oral; Days 1, 8, 15 Cycles 3-8 | 40 |
| Elo / Len •Drug: Elotuzumab 10 mg/kg IV; Days 1, 8,15, 22 Cycles 1-2 10 mg/kg IV; Days 1 & 15 Cycles 3-8
Other Name: HuLuc63
•Drug: Lenalidomide 25 mg Oral; Days 1-21 days Cycles 1-24
Other Name: REVLIMID
Elotuzumab: 10 mg/kg IV; Days 1, 8,15, 22 Cycles 1-2 10 mg/kg IV; Days 1 & 15 Cycles 3-8
Lenalidomide: 25 mg Oral; Days 1-21 days Cycles 1-24 | 11 |
| Total | 51 |
Baseline characteristics
| Characteristic | Elo / Len / Dex | Elo / Len | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 17 Participants | 3 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 8 Participants | 31 Participants |
| Age, Continuous | 62 years | 62 years | 62 years |
| ECOG Performance Status 00 - Fully Active | 27 Participants | 7 Participants | 34 Participants |
| ECOG Performance Status 01 - Restricted | 12 Participants | 4 Participants | 16 Participants |
| ECOG Performance Status 02 - Ambulatory | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants | 11 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 31 Participants | 11 Participants | 42 Participants |
| Region of Enrollment United States | 40 participants | 11 participants | 51 participants |
| Sex: Female, Male Female | 26 Participants | 6 Participants | 32 Participants |
| Sex: Female, Male Male | 14 Participants | 5 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 40 | 0 / 11 |
| other Total, other adverse events | 40 / 40 | 11 / 11 |
| serious Total, serious adverse events | 8 / 40 | 1 / 11 |
Outcome results
Primary
Percent of Patients Who Are Progression Free at 2 Years
Percent of patients who are alive and without documented progression after at least 2-years of follow-up. All patients who receive study treatment are assessed including those who have died or lost to follow-up prior to 2-years. Progression was defined as an increase in SPEP \[25% and an absolute increase of 0.5g/d\] or UPEP \[25% and an absolute increase of 200mg/24hours\] on 2 successive evaluations as determined by the IMWG response criteria or documented progression by the FreeLite progressive disease criteria in the absence of serum or urine involvement.
Time frame: 2 Years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elo / Len / Dex | Percent of Patients Who Are Progression Free at 2 Years | 45.0 percentage of participants |
| Elo / Len | Percent of Patients Who Are Progression Free at 2 Years | 36.4 percentage of participants |
Secondary
Objective Response Percent
Percent of patients with objective response defined as partial response or better based on the International Myeloma Working Group Response (IMWG) criteria
Time frame: 2 Years from start of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Elo / Len / Dex | Objective Response Percent | 82.5 percentage of participants |
| Elo / Len | Objective Response Percent | 72.7 percentage of participants |
Secondary
Overall Survival
Time from initiation of therapy to death
Time frame: From start of treatment up to +/- 60 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Elo / Len / Dex | Overall Survival | 50.5 months |
| Elo / Len | Overall Survival | 60.2 months |
Secondary
Time to Progression
Time from initiation of therapy to progression defined by the IMWG criteria.
Time frame: From start of treatment up to +/- 60 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Elo / Len / Dex | Time to Progression | 56.1 months |
| Elo / Len | Time to Progression | 56.2 months |