Using leflunomide to treat high-risk smoldering multiple myeloma in African-American and European-American patients

Phase 2 Trial of Leflunomide in African-American and European-American Patients With High-Risk Smoldering Multiple Myeloma

This study is testing if leflunomide can help African-American and European-American patients with high-risk smoldering multiple myeloma avoid disease progression and improve their quality of life.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 56 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: City of Hope Medical Center (Academic / other)
• Drugs / interventions: chemotherapy, radiation, prednisone
• Locations: 4 sites (Duarte, California and 3 other locations)
• Trial ID: NCT05014646 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the effects of leflunomide, an immunomodulatory drug, on patients with high-risk smoldering multiple myeloma. The study aims to evaluate the drug's anti-myeloma activity by assessing freedom from disease progression over two years, as well as its safety and tolerability. Secondary objectives include analyzing treatment-related toxicities, overall survival rates, and quality of life impacts. Patients will receive leflunomide orally once daily for 28-day cycles, with follow-up assessments conducted yearly after treatment completion.

Who should consider this trial

Good fit: Ideal candidates are African-American or European-American adults aged 18 and older with a diagnosis of high-risk smoldering multiple myeloma.

Not a fit: Patients with low-risk smoldering multiple myeloma or those who do not identify as African-American or European-American may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could delay the progression of multiple myeloma in high-risk patients, potentially improving their quality of life and survival rates.

How similar studies have performed: While this approach is novel in its specific focus on high-risk smoldering multiple myeloma in these populations, similar studies using immunomodulatory treatments have shown promise in other contexts.

Eligibility criteria

Inclusion Criteria:

* 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)
* Total bilirubin \< 1.5 x ULN
* Calculated creatinine clearance (CrCl) \>= 30 mL/min per 24-hour urine collection or the Cockcroft-Gault formula
* Negative serum or urine beta-human chorionic gonadotropin (HCG) test (female patient of childbearing potential only), to be performed locally within the screening period
* Negative for tuberculosis antigen (e.g. T-Spot test)
* Negative for hepatitis A, B, or C infection
* Adequate pulmonary function as defined by forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) \>= 50% of predicted by pulmonary function testing
* Agreement by females of childbearing potential and sexually active males to use an effective method of contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for three months following duration of study participation. The effects of study treatment on a developing fetus have the potential for teratogenic or abortifacient effects. Should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately

  * A female of childbearing potential is defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months

Exclusion Criteria:

* 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
* Acute active infection requiring systemic therapy within 2 weeks prior to enrollment
* Pre-existing liver disease
* Known human immunodeficiency virus (HIV) infection
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to leflunomide and cholestyramine
* Non-hematologic malignancy within the past 3 years aside from the following exceptions:

  * Adequately treated basal cell or squamous cell skin cancer
  * Carcinoma in situ of the cervix
  * Prostate cancer \< Gleason grade 6 with a stable prostate specific antigen (PSA)
  * Successfully treated in situ carcinoma of the breast
* Clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or the patient's ability to give informed consent
* Pregnant women and women who are lactating. Leflunomide has potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is enrolled on this study
* Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc.
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Where this trial is running

Duarte, California and 3 other locations

• City of Hope Medical Center — Duarte, California, United States (Recruiting)
• Wayne State University/Karmanos Cancer Institute — Detroit, Michigan, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (Recruiting)
• Atrium Health University City/LCI-University — Charlotte, North Carolina, United States (Recruiting)

Study contacts

• Principal investigator: Michael A Rosenzweig — City of Hope Comprehensive Cancer Center

Conditions Smoldering Plasma Cell Myeloma