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

Smoldering Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02279394
• Other study ID #: 14-338
• Status: Completed
• Phase: Phase 2
• Start date: December 11, 2014
• Est. completion date: January 26, 2022

Study information

• Verified date: May 2023
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: January 26, 2022
• Est. primary completion date: December 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Smoldering Multiple Myeloma
• Smoldering Myeloma

Intervention

Drug:
• 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

Locations

Country	Name	City	State
United States	University of Maryland	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Eastern Maine Medical Center	Brewer	Maine
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University of Chicago	Chicago	Illinois
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	St Francis Hospital and Medical Center	Hartford	Connecticut

Sponsors (6)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Blood Cancer Research Partnership, Bristol-Myers Squibb, Celgene, Multiple Myeloma Research Consortium, The Leukemia and Lymphoma Society

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	2 Years
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	2 Years from start of treatment
Secondary	Time to Progression	Time from initiation of therapy to progression defined by the IMWG criteria.	From start of treatment up to +/- 60 months
Secondary	Overall Survival	Time from initiation of therapy to death	From start of treatment up to +/- 60 months