RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2022-03-07

Study Completion:2025-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05014646

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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)

Inclusion Criteria

Exclusion 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

* 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)

Contacts and Locations

Principal Investigator

Michael A Rosenzweig

PRINCIPAL_INVESTIGATOR

City of Hope Comprehensive Cancer Center

Study Locations (Sites)

City of Hope Medical Center

Duarte, California, 91010

United States

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

Atrium Health University City/LCI-University

Charlotte, North Carolina, 28204

United States

Collaborators and Investigators

Sponsor: City of Hope Medical Center

Michael A Rosenzweig, PRINCIPAL_INVESTIGATOR, City of Hope Comprehensive Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-03-07

Study Completion Date2025-12-31

Study Record Updates

Study Start Date2022-03-07

Study Completion Date2025-12-31

Terms related to this study

Additional Relevant MeSH Terms

Smoldering Plasma Cell Myeloma