None listed
Conditions
Interventions
Drug : Talquetamab
Cycle 1 Day 1 0.01mg/kg
Cycle 1 Day 3 0.06mg/kg
Cycle 1 Day 5 0.4mg/kg
Cycle 1 Day 8 0.8mg/kg
Cycle 2 -24 Day 1 1 0.8mg/kg
Lenalidomide
Cycle 1 -24 Day 1 - 28 once daily 5-10mg
Sponsors
Chonnam National University Hwasun Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 6.1 Inclusion Criteria 6.1.1 Age =18 years. 6.1.2 Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. 6.1.3 Diagnosis of multiple myeloma according to the International Myeloma Working Group (IMWG) criteria.¹?,¹¹ 6.1.4 Patients who have completed induction therapy, high-dose therapy, and autologous hematopoietic stem cell transplantation and have received lenalidomide maintenance therapy for either 2 or 3 years. Patients must be receiving lenalidomide monotherapy at a dose of 5–10 mg. 6.1.5 Response and MRD status Patients must maintain a very good partial response (VGPR) or better according to the IMWG criteria, without evidence of relapsed or progressive disease. Patients must be confirmed as MRD-positive by EuroFlow multiparameter flow cytometry at a sensitivity threshold of 10?5. MRD positivity during lenalidomide maintenance therapy is defined as MRD positivity confirmed by at least one MRD assessment performed after 2 years (±3 months) or 3 years (±3 months) of lenalidomide monotherapy maintenance. 6.1.6 Adequate organ function, defined as follows: Absolute neutrophil count (ANC) =0.75 × 10?/L Platelet count =50 × 10?/L; for patients with bone marrow involvement by multiple myeloma, a platelet count =30 × 10?/L is permitted Hemoglobin =8 g/dL Creatinine clearance (CrCl) =30 mL/min (see Appendix 20-3) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3 × the upper limit of normal (ULN); patients with clinically significant liver disease or immune-mediated hepatitis are excluded Total serum bilirubin =1.5 × ULN; exceptions may be permitted at the investigator’s discretion when a clearly established nonmalignant cause unrelated to hepatic injury, such as Gilbert syndrome, is present 6.1.7 No clinically significant extramedullary disease associated with multiple myeloma, including central nervous system involvement. 6.1.8 Ability to receive medications orally or subcutaneously. 6.1.9 Any toxicities resulting from prior therapy must have completely resolved or stabilized at Grade 1 or lower. 6.1.10 No clinically uncontrolled bleeding. 6.1.11 Each patient must sign an informed consent form indicating that the patient understands the purpose of the clinical trial and the required procedures and voluntarily agrees to participate. The patient must also be willing and able to comply with the prohibitions and restrictions specified in this treatment guideline, as described in the informed consent form. 6.1.12 Women of childbearing potential, including premenopausal women and women who have been amenorrheic or menopausal for no more than 1 year, must have a negative serum or urine pregnancy test before study initiation and agree to use effective contraception throughout the study and for a specified period after study completion. Male participants must also agree to comply with the contraceptive requirements during the study and for a specified period after study completion.
Exclusion criteria
Exclusion criteria: 6.2 Exclusion Criteria 6.2.1 Relapsed or progressive disease according to the International Myeloma Working Group (IMWG) criteria. 6.2.2 Prior treatment with any GPRC5D-targeted therapy. 6.2.3 Any active or clinically uncontrolled infection. Patients for whom the investigator considers the addition of talquetamab inappropriate because of severe or recurrent infections will also be excluded. 6.2.4 Baseline neurological abnormalities that would interfere with the assessment of neurotoxicity. Patients will be excluded if the investigator determines that they are at increased risk of neurological toxicity associated with talquetamab because of uncontrolled epilepsy, severe cognitive impairment, dementia, significant ataxia or gait disturbance, or another comparable neurological condition. 6.2.5 Clinically significant comorbidities, including any of the following: Myocardial infarction within the previous 6 months, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, or a history of severe coronary artery disease Cardiac arrhythmia of Grade 2 or higher according to the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0, or a clinically significant electrocardiographic abnormality Baseline QT interval corrected using Fridericia’s formula (QTcF) >470 ms on a 12-lead electrocardiogram at screening; patients with a pacemaker may be enrolled Left ventricular ejection fraction (LVEF) <40% as assessed by echocardiography or multigated acquisition (MUGA) scan, or another clinically significant abnormal cardiac finding Uncontrolled hypertension, defined as a mean systolic blood pressure =160 mmHg or a mean diastolic blood pressure =100 mmHg despite adequate medical management Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <60% of the predicted value or a history of asthma within the previous 2 years. Patients with known or suspected COPD must undergo pulmonary function testing at screening. 6.2.6 Surgery requiring general anesthesia within 2 weeks before screening. 6.2.7 A history of malignancy other than multiple myeloma within the previous 5 years. However, patients with nonmelanoma skin cancer or carcinoma in situ of the cervix, breast, or gastrointestinal tract that has been treated with curative intent may be enrolled. Patients with a malignancy diagnosed within the previous 3 years that has been cured or is considered to have a minimal risk of recurrence may also be enrolled. 6.2.8 A serious medical or psychiatric condition, an active uncontrolled viral infection, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection, or another serious illness that, in the opinion of the treating physician, would make participation inappropriate. This includes the following: Active hepatitis B without appropriate antiviral prophylaxis or management: Positive hepatitis B surface antigen (HBsAg) without ongoing antiviral prophylaxis; or Detectable HBV DNA without antiviral treatment or an appropriate monitoring plan Uncontrolled HBV replication: Persistently detectable and uncontrolled HBV DNA at the time of enrollment despite antiviral therapy An excessive risk of HBV reactivation during immunotherapy, as determined by the investigator: The risk of HBV reactivation during talquetamab-based immunotherapy is considered clinically unacceptable, even when antiviral prophylaxis or preemptive treatment is f
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Measurable residual disease (MRD) negativity rate assessed by EuroFlow multiparameter flow cytometry at a sensitivity of 10?5 | — |
Secondary
| Measure | Time frame |
|---|---|
| Measurable residual disease (MRD) negativity rate at Cycle 6, assessed by EuroFlow multiparameter flow cytometry at a sensitivity of 10?6 among participants evaluable for MRD at Cycle 6;Proportion of participants who achieve MRD negativity at Cycle 6 at a sensitivity of 10?5 and remain MRD-negative at all scheduled assessments for 1 year thereafter;Progression-free survival (PFS), defined as the time from initiation of talquetamab treatment to IMWG-defined disease progression or death from any cause, whichever occurs first;Overall survival (OS), defined as the time from initiation of talquetamab treatment to death from any cause;Time to best MRD response, defined as the time from initiation of talquetamab treatment to the date on which the deepest MRD response is first documented;Incidence and severity of adverse events graded according to NCI-CTCAE Version 5.0, including infections, cytokine release syndrome (CRS), neurotoxicity including ICANS, hypogammaglobulinemia, skin reactions, nail disorders, oral and taste-related adverse events, and weight loss;QOL evaluation : Health-related quality-of-life scores and changes from baseline assessed using the Korean Version 3.0 of the EORTC QLQ-C30, Changes from baseline in immunotherapy-related symptoms, functional impairment, and quality of life assessed using the Immunotherapy-Related Symptom and Quality of Life Assessment (IRS-QoL) | — |
Countries
Korea, Republic of
Contacts
Public ContactSUNG-HOON JUNG
Chonnam National University Hwasun Hospital
Outcome results
None listed