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

NCT ID: NCT02279394

Last Updated: 2023-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-11
• Study Completion Date: 2022-01-26

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.

Conditions

Smoldering Myeloma; Smoldering Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Elotuzumab

Intervention Type: DRUG

10 mg/kg IV; Days 1, 8,15, 22 Cycles 1-2 10 mg/kg IV; Days 1 \& 15 Cycles 3-8

Lenalidomide

Intervention Type: DRUG

25 mg Oral; Days 1-21 days Cycles 1-24

Dexamethasone

Intervention Type: DRUG

40 mg Oral; Days 1, 8, 15, 22 Cycles 1-2 40 mg Oral; Days 1, 8, 15 Cycles 3-8

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

Group Type: EXPERIMENTAL

Elotuzumab

Intervention Type: DRUG

10 mg/kg IV; Days 1, 8,15, 22 Cycles 1-2 10 mg/kg IV; Days 1 \& 15 Cycles 3-8

Lenalidomide

Intervention Type: DRUG

25 mg Oral; Days 1-21 days Cycles 1-24

Interventions

Elotuzumab

10 mg/kg IV; Days 1, 8,15, 22 Cycles 1-2 10 mg/kg IV; Days 1 \& 15 Cycles 3-8

Intervention Type: DRUG

Lenalidomide

25 mg Oral; Days 1-21 days Cycles 1-24

Intervention Type: DRUG

Dexamethasone

40 mg Oral; Days 1, 8, 15, 22 Cycles 1-2 40 mg Oral; Days 1, 8, 15 Cycles 3-8

Intervention Type: DRUG

Other Intervention Names

HuLuc63; REVLIMID; Decadron

Eligibility Criteria

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Celgene

INDUSTRY

Sponsor Role: collaborator

Blood Cancer Research Partnership

OTHER

Sponsor Role: collaborator

Multiple Myeloma Research Consortium

NETWORK

Sponsor Role: collaborator

The Leukemia and Lymphoma Society

OTHER

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Irene Ghobrial, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Irene Ghobrial, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Colorado Blood Cancer Institute

Denver, Colorado, United States

St Francis Hospital and Medical Center

Hartford, Connecticut, United States

University of Chicago

Chicago, Illinois, United States

Eastern Maine Medical Center

Brewer, Maine, United States

University of Maryland

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

Countries

United States

References

Kazandjian D, Diamond B, Papadimitriou M, Hill E, Sklavenitis-Pistofidis R, Ziccheddu B, Blaney P, Chojnacka M, Durante M, Maclachlan K, Young R, Usmani S, Davies F, Getz G, Ghobrial I, Korde N, Morgan G, Maura F, Landgren O. Genomic Profiling to Contextualize the Results of Intervention for Smoldering Multiple Myeloma. Clin Cancer Res. 2024 Oct 1;30(19):4482-4490. doi: 10.1158/1078-0432.CCR-24-0210.

Reference Type: DERIVED

PMID: 38652812 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

14-338

Identifier Type: -

Identifier Source: org_study_id