Alpe d'Huez Study: A Parallel Two-Cohort Study of Linvoseltamab in Addition to Lenalidomide (L2) During Maintenance Therapy of NDMM to Deepen Responses or Redrive MRD Negativity After Relapse
The purpose of this study is to determine whether giving linvoseltamab with lenalidomide during maintenance treatment to participants with multiple myeloma will: 1. Get rid of any residual multiple myeloma cells in participants' bodies which is known as minimal residual disease negative (MRD-) status. For participants that start the study with residual multiple myeloma cells in participants' bodies: to determine how long you remain MRD-. 2. Increase the length of time that participants' disease is controlled. For participants with relapsed disease, to determine whether participants can re-attain MRD- status. 3. Increase the length of time that participants' disease responds to treatment. The researchers also want to find out the effects that linvoseltamab has on participants and participants' condition.
• Diagnosis of newly-diagnosed multiple myeloma (NDMM) per International Myeloma Working Group (IMWG) documented initially prior to any treatment (Kumar et al., 2016).
• Documentation of having received a triplet or quadruplet based initial combination therapy containing at least two of the following: Immunomodulatory drug (IMiD), proteosome inhibitor (PI), and/or anti-cluster of differentiation 38 (anti-CD38).
• Documentation of receiving induction therapy with or without high-dose melphalan with autologous stem cell transplant (HDM-ASCT) and receiving lenalidomide maintenance therapy ≤ 12 months.
‣ Cohort 1: at the time of assessment, the patient's current response is a partial response (PR), very good partial response (VGPR), or complete response (CR) but MRD+ by the FDA-cleared next-generation sequencing (NGS) Adaptive clonoseq assay.
⁃ Cohort 2: at the time of assessment, the patient has a relapse from their initial complete response (CR) (\<CR response are ineligible) post induction but do not meet criteria for IMWG progression (eg, patients who no longer meet criteria for CR but whose M-protein is ≤ 0.5 g/dL and/or immunofixation has turned positive, and/or have converted to MRD+ by the FDA-cleared NGS Adaptive clonoseq assay).
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 3 (Appendix A)
• Adequate organ function
‣ Absolute neutrophil count (ANC) ≥ 1000/microlitre (unless patient has ethnic neutropenia)
⁃ Platelets ≥ 50,000/microlitre
⁃ Hemoglobin ≥ 8 g/dL (transfusions permitted)
⁃ Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN) or direct bilirubin ≤ ULN for patients with total bilirubin levels \> 1.5 ULN (except patients with Gilbert's syndrome who must have a total bilirubin of \< 3 X ULN)
⁃ Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SGPT)) ≤ 3 X ULN
⁃ Serum creatinine ≤ 1.5 X ULN (except if due to myeloma) or calculated estimated glomerular filtration rate (eGFR)/creatinine clearance (CrCl) (by Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease, or Cockcroft-Gault) ≥ 15 mL/min/1.73 m2
• Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 90 days following the last dose of study treatment.
• Willing and able to provide written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.
• Willing and able to comply with clinic visits and study-related procedures.