Phase 2 Trial of Leflunomide in Patients With High-Risk Smoldering Multiple Myeloma
Overview
- Phase
- Phase 2
- Intervention
- Leflunomide
- Conditions
- Smoldering Plasma Cell Myeloma
- Sponsor
- City of Hope Medical Center
- Locations
- 1
- Primary Endpoint
- Overall survival
- Status
- Withdrawn
- Last Updated
- 6 years ago
Overview
Brief Summary
This phase II trial studies how well leflunomide works in treating patients with high-risk smoldering multiple myeloma. Leflunomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the anti-myeloma activity of leflunomide, when given as a single agent, as assessed by freedom from progression at 2-years. 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 QLQ-C30) 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) 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 every 28 days.
Investigators
Eligibility Criteria
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)
- •Platelet count \>= 50,000/uL. Platelet transfusions are not allowed within 14 days of platelet assessment
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 \< 40 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, computer 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%
Arms & Interventions
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.
Intervention: Leflunomide
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.
Intervention: Quality-of-Life Assessment
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.
Intervention: Questionnaire Administration
Outcomes
Primary Outcomes
Overall survival
Time Frame: Up to 2 years
Overall survival will be estimated using the product-limit method of Kaplan and Meier.
Progression to multiple myeloma
Time Frame: Up to 2 years
Progression to multiple myeloma in the absence of increased calcium level, renal dysfunction, anemia, and destructive bone lesions (CRAB) features, orto symptomatic multiple myeloma that requires therapy will be assessed.
Secondary Outcomes
- Incidence of adverse events (AEs)(Up to 30 days post treatment)
- Overall response rate (ORR)(Up to 2 years)
- Freedom from progression(Up to 2 years)
- Change in quality of life(Baseline up to 2 years)