Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma

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City of Hope Medical Center

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Updated on 19 February 2024

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cancer

hysterectomy

platelet count

absolute neutrophil count

leflunomide

neutrophil count

oophorectomy

prednisone

multiple myeloma

beta-human chorionic gonadotropin

anti-inflammatory drugs

hepatitis

bilateral oophorectomy

tuberculosis

platelet transfusions

abortifacient

smoldering myeloma

spot test

removal of ovaries

smoldering multiple myeloma

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.

Description

PRIMARY OBJECTIVE:

I. To estimate the anti-myeloma activity of leflunomide, when given as a single agent, as assessed by 6-month progression-free response rate based on International Myeloma Working Group (IMWG) criteria.

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of single agent leflunomide. II. To summarize and assess toxicities by type, frequency, severity, attribution, time course and duration.

III. To estimate overall and progression-free survival probabilities. IV. To estimate response rate and duration of response. V. 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 QLQC30) Score version (v)3.0.

EXPLORATORY OBJECTIVES:

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.

OUTLINE

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

After the completion of study treatment, patients are followed up at 30 days, every 28 days until an alternative myeloma therapy has commenced or until disease progression, and then up to 6 months.

Details

Condition	Smoldering Plasma Cell Myeloma
Age	18-100 years
Treatment	Quality-of-Life Assessment, Leflunomide
Clinical Study Identifier	NCT04370483
Sponsor	City of Hope Medical Center
Last Modified on	19 February 2024

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Eligibility		Yes	No	Not Sure
Inclusion Criteria
	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
	Negative serum or urine beta-human chorionic gonadotropin (B-HCG) test (female patient of childbearing potential only), to be performed locally within the screening period
	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
	Has not undergone a hysterectomy or bilateral oophorectomy
	Has not been naturally postmenopausal for at least 24 consecutive months
	Negative for tuberculosis antigen (e.g. T-Spot test)
	Negative for hepatitis A, B, or C infection
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 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
	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)

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Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma