A Protocol to Assess the Safety, Efficacy, and Pharmacokinetics of Continuous Subcutaneous Administration of Low-dose Lenalidomide (STAR-LLD) for the Treatment of Multiple Myeloma (MM)
Primary Objective • Assess the safety and tolerability of low-dose lenalidomide administered by continuous subcutaneous (SC) infusion (STAR-LLD) in combination with dexamethasone and a proteasome inhibitor (PI). Secondary Objectives * • To establish the pharmacokinetic (PK) profile of STAR-LLD at a defined infusion rate targeting steady-state blood concentrations. * • Evaluate changes in efficacy indicators including objective response rate (ORR), progression-free survival (PFS), and duration of response (DOR). Exploratory Objective * To assess the impact of STAR-LLD on patient reported symptoms and outcomes. Primary Endpoints * The grade, frequency, and relationship of treatment-emergent adverse events (TEAEs) including adverse events of special interest (AESIs): (gastrointestinal \[GI\] toxicity, fatigue, hematologic toxicity, rash (non-infusion site). * The observation of dose-limiting toxicities (DLTs) of STAR-LLD during Cycle 1. Secondary Endpoints •• Blood concentrations of lenalidomide at on Day 1 and at steady state. * Changes in biomarkers during treatment. * Rate of complete response, very good partial response (VGPR), partial response (PR), stable disease (SD), and progressive disease. * Determination of ORR, PFS, and DOR
• Male or female ≥18 years at the time of informed consent.
• Autologous stem cell transplant (ASCT) ineligible.
• SARS -CoV2 virus (COVID)-19 negative.
• A prior diagnosis of MM as defined by International Myeloma Working Group (IMWG) criteria (Appendix 7).
• Documented measurable disease following first line therapy defined as:
‣ Serum monoclonal protein ≥1.0 g/dL by protein electrophoresis.
⁃ ≥200 mg/24 hours of monoclonal protein in the urine on 24-hour electrophoresis.
⁃ Serum free light chain (SFLC) ≥10 mg/dL AND abnormal serum kappa to lambda free light chain (FLC) ratio.
• Intended to be treated in 2nd line or greater with lenalidomide, dexamethasone, and a PI.
• Proteasome inhibitor sensitive defined as progression free for \> 6 months from cessation of PI or never received a prior PI.
• Progression per IMWG criteria on the most recent line of therapy.
• Eastern Cooperative Oncology Group (ECOG-Appendix 1) performance status ≤2 (patients with a performance status of 3 based solely on bone pain secondary to MM may be eligible following consultation and approval by the Medical Monitor).
⁃ Willing to comply with the protocol defined Lenalidomide Pregnancy Risk Minimization Plan for the prevention of pregnancy (Appendix 5). Females of childbearing potential (FCBP) must have a medically supervised negative serum or urine pregnancy test 4-14 days prior to planned start of treatment and again 24 hours prior to initiation of study medication. All FCBP must agree to either commit to continued abstinence from sexual intercourse or begin TWO acceptable methods of birth control AT THE SAME TIME, at least 28 days before receiving the first dose of STAR-LLD. FCBP must also agree to ongoing pregnancy testing. Males must agree to use a latex or synthetic condom during sexual contact with a FCBP from the time of starting study treatment through 28 days after the last dose, even if they have had a vasectomy.
⁃ Able to take anti-thrombotic prophylaxis.
⁃ The following laboratory results must be met during screening:
∙ ANC ≥1,000 cells/mm3 (1.0 x 109/L).
‣ Platelet count ≥75,000 cells/mm3 (75 x 109/L).
‣ Hemoglobin ≥8.0 g/dL (red blood cell (RBC) transfusions are permitted prior to initiation of study drug if hemoglobin is stable for 72 hours).
‣ Total bilirubin ≤1.5 x upper limit of normal (ULN), or patient diagnosed with Gilberts syndrome with a total bilirubin \<5.0 x ULN that has been reviewed and approved by the Medical Monitor.
‣ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 x ULN.
‣ Calculated creatinine clearance ≥60 mL/min. Appendix 4
‣ Negative pregnancy test for FCBP (must be obtained within 4-14 days before the initiation of study drug.
⁃ The following criteria must be met within 72 hours prior to first administration of continuous infusion STAR-LLD:
∙ ANC ≥1,000 cells/mm3 (1.0 x 109/L).
‣ Platelet count ≥75,000 cells/mm3 (75 x 109/L).
‣ Hemoglobin ≥8.0 g/dL (RBC transfusions are permitted prior to initiation of study drug if hemoglobin is stable for 72 hours).
‣ Calculated creatinine clearance ≥60 mL/min. Appendix 4
‣ Negative pregnancy test for FCBP (must be obtained within 24 hours of first dose of study drug).
⁃ Able and willing to receive percutaneous ambulatory therapy.
⁃ Has an in-home care partner willing to receive training from a nurse for assistance with pump management.