Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma

NCT04370483 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: 19456NCI-2020-01505
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot trial studies how well leflunomide works for the treatment of patients with high-risk smoldering plasma cell myeloma, for the delay of disease progression. Anti-inflammatory drugs, such as leflunomide lower the body's immune response and are used with other drugs in the treatment of some types of cancer. The information learned from this study will help researchers to learn more about the anti-myeloma activity of leflunomide, and whether it may delay the onset of symptomatic multiple myeloma in patients with high-risk smoldering multiple myeloma.

Conditions

Smoldering Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Progressive disease

  Will be defined by International Myeloma Working Group (IMWG) criteria. Progression to overt multiple myeloma is always considered progressive disease.

  Up to 48 months

Secondary Outcomes (5)

• Incidence of adverse events

  Up to 30 days after end of treatment

• Incidence of toxicities

  Up to 30 days after the end of treatment

• Overall response rate

  From the date of first documented response (confirmed complete response [CR], very good partial response [VGPR], partial response [PR] or minor response [MR]) to documented disease relapse, progression or death, assessed up to 48 months

• Overall survival

  From start date of therapy to date of death from any cause, assessed up to 48 months

• Quality of life Questionnaire

  At baseline and every 6 cycles thereafter up to 36 cycles (end of treatment), length of one complete cycle is 28 days

Study Arms (1)

Treatment (leflunomide)

EXPERIMENTAL

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

Drug: Leflunomide; Other: Quality-of-Life Assessment

Interventions

Leflunomide DRUG

Gievn PO

Also known as: Arava, SU101

Treatment (leflunomide)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

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 have a life expectancy of \> 3 months
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• 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
• 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)
• Within 5 years of a diagnosis of high-risk smoldering multiple myeloma (MM)
• Platelet count \>= 50,000/uL. Platelet transfusions are not allowed within 14 days of platelet assessment
• Absolute neutrophil count (ANC) \>= 1000/mm\^3
• Aspartate transaminase (AST) and alanine transferase (ALT) \< 2.0 x upper limit of normal (ULN)
• Total bilirubin \< 1.5 x ULN
• Calculated creatinine clearance (CrCl) \>= 30 mL/min per 24-hour urine collection or the Cockcroft-Gault formula

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 calcium (elevated), renal failure, anemia, and bone lesions (CRAB) criteria that are attributable to conditions other than the disease under study may be eligible
• Prior diagnosis of rheumatoid arthritis
• Prior allogeneic transplant
• Acute active infection requiring systemic therapy within 2 weeks prior to enrollment

Sponsors & Collaborators

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

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Smoldering Multiple Myeloma

Interventions

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)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Michael A Rosenzweig

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2020
• First Posted: May 1, 2020
• Study Start: October 8, 2020
• Primary Completion (Estimated): November 10, 2026
• Study Completion (Estimated): November 10, 2026
• Last Updated: January 5, 2026

Record last verified: 2025-12

Locations

US (1)