Aggressive Smoldering Curative Approach Evaluating Novel Therapies (ASCENT): A Phase 2 Trial of Induction Consolidation and Maintenance in Subjects With High Risk Smoldering Multiple Myeloma (SMM)

R
Rafat Abonour, MD

Primary Investigator

Overview

This study evaluates the use of carfilzomib, lenalidomide, daratumumab, and dexamethasone in subjects with high-risk smoldering multiple myeloma (SMM).

Description

This study is a multi-center phase 2 study of carfilzomib, lenalidomide, daratumumab, and dexamethasone in subjects with high-risk smoldering multiple myeloma (SMM). Myeloma remains incurable with the current approaches. The typical natural history of myeloma is one of repeated relapses, accompanied by genetic evolution and development of new abnormalities, which are often responsible for drug resistance. The presence of a precursor phase of smoldering myeloma, and the ability to identify those at the highest risk of progression, sets the stage to examine the possibility that we can cure the disease through early intervention. In order to potentially achieve this, we need to develop a highly effective combination that includes the most active drugs from different classes. Carfilzomib in combination with lenalidomide and dexamethasone results in high response rates and deep responses in subjects with newly diagnosed myeloma. Daratumumab in combination with lenalidomide results in high response rates in relapsed refractory disease. All these drugs are well tolerated and subjects are able to stay on them long term as a maintenance treatment. The combination of the carfilzomib, lenalidomide, daratumumab and dexamethasone presents the potential to enhance the effectiveness of the regimens. We hypothesize that this combination will lead to deep response including a higher proportion of minimal residual disease (MRD) negative disease among those with high risk smoldering myeloma and may translate into cure or long term disease quiescence.

Eligibility

You may be eligible for this study if you meet the following criteria:

  • Conditions:
    smoldering multiple myeloma,Smoldering Multiple Myeloma
  • Age: Between 18 Years - 80 Years
  • Gender: All

Inclusion Criteria
High risk smoldering myeloma, which is untreated
Measurable disease
Previously untreated
Negative pregnancy test
Exclusion Criteria
Monoclonal gammopathy of undetermined significance (MGUS), standard risk smoldering myeloma, symptomatic myeloma, or light chain amyloidosis with organ involvement
Diagnosed or treated for another malignancy less than or equal to 2 years before trial enrollment or previously diagnosed with another malignancy and have any evidence of residual disease
Pregnant women
Nursing women
Men or women of childbearing potential who are unwilling to employ adequate contraception
Other concurrent chemotherapy, or any ancillary therapy considered investigational
Evidence of current uncontrolled cardiovascular conditions, including hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
Known human immunodeficiency virus (HIV) positive
Known hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients or known sensitivity to mammalian-derived products
Known allergies, hypersensitivity, or intolerance to trial drugs


Additional Information:
Participants will not be paid for their participation.

Updated on 20 Nov 2022. Study ID: 1801025157 (ASCENT-BS001)

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