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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT05014646
Recruitment Status : Recruiting
First Posted : August 20, 2021
Last Update Posted : April 13, 2022
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

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.

Condition or disease Intervention/treatment Phase
Smoldering Plasma Cell Myeloma Drug: Cholestyramine Drug: Leflunomide Phase 2

Detailed Description:


I. To evaluate the anti-myeloma activity of leflunomide, when given as a single agent, as assessed by freedom from progression at 2-years.

II. To evaluate the safety and tolerability of single agent leflunomide.


I. To summarize and assess toxicities by type, frequency, severity, attribution, time course and duration.

II. To estimate overall and progression-free survival probabilities. III. To estimate response rate and duration of response. IV. To describe the impact of treatment on quality of life, as assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score version (v)3.0.


I. To characterize the molecular evolution of the tumor cells. II. To evaluate whether specific genetic subtypes respond differently to leflunomide.

III. To evaluate the role of immune cells in the progression of smoldering multiple myeloma (SMM).

IV. To evaluate the role of leflunomide in modulating the immune system. V. To examine the relationship between immunological changes and disease progression.


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

After completion of study treatment, patients are followed up yearly.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Phase 2 Trial of Leflunomide in African-American and European-American Patients With High-Risk Smoldering Multiple Myeloma
Actual Study Start Date : March 7, 2022
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : December 31, 2024

Arm Intervention/treatment
Experimental: Treatment (leflunomide)
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
Given PO
Other Names:
  • Cholybar
  • Colestyramine
  • Duolite AP143 Resin
  • Questran
  • Questran Light

Drug: Leflunomide
Given PO
Other Names:
  • Arava
  • SU101

Primary Outcome Measures :
  1. Progression to multiple myeloma [ Time Frame: At 2 years ]
  2. Incidence of adverse events [ Time Frame: Up to 30 days after last dose ]
    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.

Secondary Outcome Measures :
  1. Overall survival [ Time Frame: From start of treatment to death, or last follow-up, whichever comes first, assessed up to 2 years ]
  2. Progression-free survival [ Time Frame: From randomization to progression or death or loss to follow up, whichever comes first, assessed up to 2 years ]
  3. Freedom-from progression [ Time Frame: From start of treatment to the first assessment showing symptomatic disease, assessed up to 2 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT05014646

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United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Michael A. Rosenzweig    626-256-4673 ext 62405   
Principal Investigator: Michael A. Rosenzweig         
United States, Michigan
Wayne State University/Karmanos Cancer Institute Not yet recruiting
Detroit, Michigan, United States, 48201
Contact: Jeffrey A. Zonder    800-527-6266   
Principal Investigator: Jeffrey A. Zonder         
United States, North Carolina
Atrium Health University City/LCI-University Not yet recruiting
Charlotte, North Carolina, United States, 28262
Contact: Saad Z. Usmani    980-442-4393   
Principal Investigator: Saad Z. Usmani         
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
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Principal Investigator: Michael A Rosenzweig City of Hope Comprehensive Cancer Center
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Responsible Party: City of Hope Medical Center Identifier: NCT05014646    
Other Study ID Numbers: 21049
NCI-2021-07263 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
21049 ( Other Identifier: City of Hope Medical Center )
P30CA033572 ( U.S. NIH Grant/Contract )
First Posted: August 20, 2021    Key Record Dates
Last Update Posted: April 13, 2022
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Smoldering Multiple Myeloma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Precancerous Conditions
Cholestyramine Resin
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anticholesteremic Agents
Hypolipidemic Agents
Lipid Regulating Agents