Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma in African-American and European-American Patients

NCT05014646 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 21049NCI-2021-07263P30CA033572
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 4

Brief Summary

This phase II trial studies the effects of leflunomide in treating African-American and European-American patients with high-risk smoldering multiple myeloma. Leflunomide is used to decrease the body's immune response and may delay the symptoms of multiple myeloma in patients of African-American and European decent.

Conditions

Smoldering Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (2)

• Progression to multiple myeloma

  At 2 years

• Incidence of adverse events

  Measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5. Will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, serum concentration of the active leflunomide metabolite, probable association with the study treatment and reversibility or outcome.

  Up to 30 days after last dose

Secondary Outcomes (3)

• Overall survival

  From start of treatment to death, or last follow-up, whichever comes first, assessed up to 2 years

• Progression-free survival

  From randomization to progression or death or loss to follow up, whichever comes first, assessed up to 2 years

• Freedom-from progression

  From start of treatment to the first assessment showing symptomatic disease, assessed up to 2 years

Study Arms (1)

Treatment (leflunomide)

EXPERIMENTAL

Patients receive leflunomide PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cholestyramine; Drug: Leflunomide

Interventions

Cholestyramine DRUG

Given PO

Also known as: Cholybar, Colestyramine, Duolite AP143 Resin, Questran, Questran Light

Treatment (leflunomide)

Leflunomide DRUG

Given PO

Also known as: Arava, SU101

Treatment (leflunomide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects must have the ability to understand and the willingness to sign a written informed consent
• Patients must be age \>= 18 years
• Patients must have a life expectancy of \> 24 months
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Patients must identify as African-American OR European-American
• Patients must have a diagnosis of high risk smoldering multiple myeloma, as defined below:
• The presence of \>= 2 of the following risk factors:
• Bone marrow plasma cell percentage (BMPC%) \> 20%
• Serum M-protein \> 2 g/dL
• Free light chain ratio (FLCr) \> 20
• A diagnosis of high-risk SMM must have been made within the last 3 years
• At least 2 weeks from prior therapy to time of start of treatment. Prior therapy includes steroids (except prednisone or equivalent - up to 10 mg per day is allowed)
• Platelet count \>= 50,000/uL. Platelet transfusions are not allowed within 14 days of platelet assessment
• Absolute neutrophil count (ANC) \>= 1000/mm\^3
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.0 x upper limit of normal (ULN)

You may not qualify if:

• Prior treatment with leflunomide
• Prior treatment for smoldering multiple myeloma
• Current or planned use of other investigational agents, or concurrent biological, chemotherapy, or radiation therapy during the study treatment period. Current or planned growth factor or transfusion support until after initiation of treatment. If growth factor or transfusion support is provided between screening and start of treatment, the participant will no longer be eligible
• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:
• Hypercalcemia: serum calcium \> 0.25 mmol/L (\> 1 mg/dL) higher than the upper limit of normal or \> 2.75 mmol/L (\> 11 mg/dL)
• Renal insufficiency: creatinine clearance \< 30 mL per min or serum creatinine \> 177 umol/L (\> 2 mg/dL)
• Anemia: hemoglobin value of \> 20 g/L below the lower limit of normal, or a hemoglobin value \< 10 g/dL
• Bone lesions: one or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)-CT
• Any one or more of the following biomarkers of malignancy:
• Clonal bone marrow plasma cell percentage \>= 60%
• Involved:uninvolved serum free light chain ratio \>= 100 (Involved free light chain must be \>= 100 mg/L)
• \>= 1 focal lesions on magnetic resonance imaging (MRI) studies (\>= 5 mm in size each)
• Participants with CRAB criteria that are attributable to conditions other than the disease under study may be eligible
• Prior diagnosis of rheumatoid arthritis
• Prior allogeneic transplant

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Atrium Health University City/LCI-University

Charlotte, North Carolina, 28204, United States

Location

MeSH Terms

Conditions

Smoldering Multiple Myeloma

Interventions

Cholestyramine Resin; Leflunomide

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Polystyrenes; Plastics; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Michael A Rosenzweig

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2021
• First Posted: August 20, 2021
• Study Start: March 7, 2022
• Primary Completion (Estimated): January 16, 2027
• Study Completion (Estimated): January 16, 2027
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

US (4)