Smoldering Plasma Cell MyelomaEarly Phase 1NCT04370483
Leflunomide for the Treatment of High-Risk Smoldering Multiple Myeloma
A Early Phase 1 study testing Leflunomide and Quality-of-Life Assessment in people with Smoldering Plasma Cell Myeloma, run by City of Hope Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Smoldering Plasma Cell Myeloma
- What is being tested?
- Leflunomide and Quality-of-Life Assessment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Oct 2020to 10 Nov 2026
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
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- 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
Who cannot join
- 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)
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- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
City of Hope Medical Center
Duarte, California, 91010
About this study
Official title: Pilot Trial of Leflunomide in Patients With High-Risk Smoldering Multiple Myeloma
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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 QLQ-C30) Score version (v)3.0.
EXPLORATORY OBJECTIVES:
- 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.
- Conditions
- Smoldering Plasma Cell Myeloma
- Being tested
- Leflunomide, Quality-of-Life Assessment
- Medical subject headings
- Smoldering Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LeflunomideDrug
Also called Arava, SU101
Gievn PO
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (leflunomide) | Experimental | Patients receive leflunomide PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Leflunomide; Other: Quality-of-Life Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progressive disease
Will be defined by International Myeloma Working Group (IMWG) criteria. Progression to overt multiple myeloma is always considered progressive disease.
Measured: Up to 48 months
Secondary outcomes (5)
Incidence of adverse events
Will be defined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5 to grade toxicities. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.
Measured: Up to 30 days after end of treatment
Incidence of toxicities
Will be defined using the NCI CTCAE version 5 to grade toxicities. Will assess toxicities by type, frequency, severity, attribution, time course and duration. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.
Measured: Up to 30 days after the end of treatment
Overall response rate
The overall response rate and 95% Clopper Pearson binomial confidence interval (CI) will be calculated. Response rates will also be explored based on number/type of prior therapy(ies). Response rate (CR, VGPR, PR, or MR), based on the IMWG 2016 criteria will be calculated as the percent of evaluable patients that have confirmed CR/VGPR/PR or MR.
Measured: 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
Overall survival will be estimated using the product-limit method of Kaplan and Meier.
Measured: From start date of therapy to date of death from any cause, assessed up to 48 months
Quality of life Questionnaire
The Quality of Life Questionnaire Core 30 (QLQ-C30) scales (five functional scales, three symptom scales, a global health status / quality of life (QoL) scale, and six single items) will be summarized using descriptive statistics. Changes in reported QOL over time from baseline will also be summarized.
Measured: At baseline and every 6 cycles thereafter up to 36 cycles (end of treatment), length of one complete cycle is 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2020
- Study start8 Oct 2020
- Primary completion10 Nov 2026 (estimated)
- Study completion10 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Smoldering Plasma Cell MyelomaStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Michael A Rosenzweig, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04370483
- Sponsor's protocol ID
- 19456
- Other IDs
- NCI-2020-01505, 19456
- Status last verified
- Dec 2025
- First submitted
- 30 Mar 2020
- Last updated
- 5 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Trial of Leflunomide in Patients With High-Risk Smoldering Multiple Myeloma
- ClinicalTrials.gov ID
- NCT04370483
- Acronym / sponsor ID
- 19456
- Conditions
- Smoldering Plasma Cell Myeloma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 8 Oct 2020 (actual)
- Primary completion
- 10 Nov 2026 (estimated)
- Study completion
- 10 Nov 2026 (estimated)
- First posted
- 1 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- 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:
- 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 QLQ-C30) Score version (v)3.0.
EXPLORATORY OBJECTIVES:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (leflunomide) | Experimental | Drug: Leflunomide, Other: Quality-of-Life AssessmentPatients receive leflunomide PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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:
- 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)
Key exclusion criteria (27 listed)
- 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:
- Any one or more of the following biomarkers of malignancy:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LeflunomideAlso: Arava, SU101Gievn PO | Drug | Treatment (leflunomide) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Treatment (leflunomide) |
Primary outcome
Progressive disease
Time frame: Up to 48 months
Will be defined by International Myeloma Working Group (IMWG) criteria. Progression to overt multiple myeloma is always considered progressive disease.
5 secondary outcomes
Incidence of adverse events
Time frame: Up to 30 days after end of treatment
Incidence of toxicities
Time frame: Up to 30 days after the end of treatment
Overall response rate
Time frame: 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
Time frame: From start date of therapy to date of death from any cause, assessed up to 48 months
Quality of life Questionnaire
Time frame: At baseline and every 6 cycles thereafter up to 36 cycles (end of treatment), length of one complete cycle is 28 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael A Rosenzweig principal investigator
City of Hope Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Leflunomide and Quality-of-Life Assessment in people with Smoldering Plasma Cell Myeloma, run by City of Hope Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 5 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progressive disease (time frame: Up to 48 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2026.