E-PRISM: Phase II Trial of Elotuzumab Lenalidomide and Dexamethasone in High-Risk Smoldering Multiple Myeloma

Phase 2

Completed

Conditions: Smoldering Myeloma
Smoldering Multiple Myeloma

Interventions: Drug: Elotuzumab
Drug: Lenalidomide
Drug: Dexamethasone

Registration Number: NCT02279394

Lead Sponsor: Dana-Farber Cancer Institute

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 51

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 exclusion criteria. Bisphosphonates are not excluded
Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational. Prior therapy with bisphosphonate is allowed. Prior radiation therapy to a solitary plasmacytoma is allowed. Prior clinical trials for smoldering MM or MGUS are allowed as long as the last therapy was at least 2 months prior and there was no improvement in M spike
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
Uncontrolled intercurrent illness
History of allergic reactions attributed to compounds of similar chemical or biologic composition to elotuzumab or lenalidomide
Known seropositive for or active viral infection with human immunodeficiency virus, hepatitis B virus or hepatitis C virus. Patients who are seropositive because of hepatitis B virus vaccine are eligible

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Elo / Len / Dex	Elotuzumab	•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
Elo / Len / Dex	Lenalidomide	•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
Elo / Len / Dex	Dexamethasone	•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
Elo / Len	Elotuzumab	•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
Elo / Len	Lenalidomide	•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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Time to Progression	From start of treatment up to +/- 60 months	Time from initiation of therapy to progression defined by the IMWG criteria.
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
Overall Survival	From start of treatment up to +/- 60 months	Time from initiation of therapy to death

Trial Locations

Locations (9): Barbara Ann Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
University of Maryland
🇺🇸
Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
St Francis Hospital and Medical Center
🇺🇸
Hartford, Connecticut, United States
Colorado Blood Cancer Institute
🇺🇸
Denver, Colorado, United States
University of Chicago
🇺🇸
Chicago, Illinois, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
Eastern Maine Medical Center
🇺🇸
Brewer, Maine, United States