Multiple Myeloma
Conditions
Brief summary
The purpose of this study is to identify preventive treatments that can minimize the occurrence, severity, and duration of talquetamab-related taste changes (dysgeusia), during the prophylaxis (preventive) treatment phase, to better characterize the signs or symptoms of talquetamab-related taste changes and to better characterize the signs or symptoms of ramantamig-related taste changes.
Interventions
DRUGTalquetamab
Talquetamab will be administered subcutaneously.
DRUGProphylaxis A
Prophylaxis A will be administered orally.
DRUGProphylaxis B
Prophylaxis B will be administered orally.
DRUGProphylaxis C
Prophylaxis C will be administered orally.
DRUGProphylaxis D
Prophylaxis D will be administered topically.
DRUGRamantamig
Ramantamig will be administered subcutaneously.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Multiple myeloma (MM) according to IMWG diagnostic criteria * Were triple-class exposed (received prior treatment with a PI, an IMiD, and anti CD38 mAb) * Documented evidence of progressive disease based on investigator's determination of response by IMWG criteria on or after their last regimen * Have an Eastern Cooperative Oncology Group-performance status (ECOG-PS) of 0 or 1 at screening. Participants with ECOG-PS 2 or 3 are eligible for the study if the ECOG-PS score is related to stable physical limitations (e.g., wheelchair-bound due to prior spinal cord injury) and not related to multiple myeloma or associated therapy * Be willing and able to adhere to the lifestyle restrictions specified in the protocol
Exclusion criteria
* Contraindications or life-threatening known allergies, hypersensitivity, or intolerance to any study drug or its excipients * Stroke, transient ischemic attack, or seizure within 6 months prior to screening * Any of the following within 6 months prior to the first dose of study treatment: severe or unstable angina, myocardial infarction; major thromboembolytic event (e.g., pulmonary embolism, cerebrovascular accident), clinically significant ventricular arrythmia or heart failure New York Heart Association functional classification Class III or IV. Uncomplicated deep vein thrombosis is not considered exclusionary * Major surgery or had significant traumatic injury within 2 weeks prior to the start of administration of study treatment, or will not have fully recovered from surgery, or has major surgery planned during the time the participant is expected to be treated in the study or within 2 weeks after administration of the last dose of study treatment * A WETT score indicating severe dysgeusia at screening and confirmed prior to randomization. Also unresolved/severe dysgeusia referred by the participant or a finding in the physical examination/oral cavity inspection. Some examples include leukoplakia, prior mouth cancers, extensive dental caries, severe periodontitis, active oral infections, candidiasis, parotic gland removal, or radiotherapy with resultant xerostomia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Occurrence of Dysgeusia as Assessed by the Total Waterless Empirical Taste Test (WETT) Testing Score During the Prophylaxis Treatment Phase | Up to 12 months | Dysgeusia is defined as total WETT score of 25th percentile or below according to the Normative WETT-SA53 percentile table. Taste assessment will be performed using taste strips (WETT). Four concentrations (4=lowest concentration, 1=highest concentration) will be used for each taste quality: sweet, sour, salty, bitter, and umami. Each test kit contains 53 taste strips distributed in 4 packs; and each taste strip is numbered (1 through 53). Participants will use each strip sequentially and record the flavor on a score card provided. The test will result in a maximum (that is, best) total score of 53. The score will be graded by a qualified site staff into a normative percentile score using a provided chart. |
| Percentage of Participants With Occurrence of Severe Dysgeusia During the Prophylaxis Treatment Phase | Up to 12 months | Severe Dysgeusia is defined as a total WETT score of 10th percentile or below according to the normative WETT-SA53 percentile table. Taste assessment will be performed using taste strips (WETT). Four concentrations (4=lowest concentration, 1=highest concentration) will be used for each taste quality: sweet, sour, salty, bitter, and umami. Each test kit contains 53 taste strips distributed in 4 packs; and each taste strip is numbered (1 through 53). Participants will use each strip sequentially and record the flavor on a score card provided. The test will result in a maximum (that is, best) total score of 53. The score will be graded by a qualified site staff into a normative percentile score using a provided chart. |
| Time to the First Onset of Severe Dysgeusia During the Prophylaxis Treatment Phase | Up to 12 months | Time to the first onset of severe dysgeusia is defined as time from the first dose date of talquetamab to the first onset date of severe dysgeusia according to the total WETT score. For participants without severe dysgeusia, time to the first onset will be censored. Taste assessment will be performed using taste strips (WETT). Four concentrations (4=lowest concentration, 1=highest concentration) will be used for each taste quality: sweet, sour, salty, bitter, and umami. Each test kit contains 53 taste strips distributed in 4 packs; and each taste strip is numbered (1 through 53). Participants will use each strip sequentially and record the flavor on a score card provided. The test will result in a maximum (that is, best) total score of 53. The score will be graded by a qualified site staff into a normative percentile score using a provided chart. |
| Percentage of Participants Who Report Resolution/Improvement of Dysgeusia During the Prophylaxis Treatment Phase | End of Month 3 | Resolution/improvement is defined as 2 potential scenarios: 1) A dysgeusia downgraded to dysgeusia-free, that is (i.e.,) total WETT score of 25th percentile or below at visits prior to the end of month 3 becomes total WETT score above 25th percentile at the end of month 3. 2) Severe dysgeusia downgraded to non-severe dysgeusia, i.e., total WETT score of 10th percentile or below prior to the end of month 3 becomes total WETT score above 10th percentile at the end of month 3. Taste assessment will be performed using taste strips (WETT). Four concentrations will be used for each taste quality: sweet, sour, salty, bitter, \& umami. Each test kit contains 53 taste strips; numbered (1 through 53). Participants will use each strip sequentially and record flavor on score card provided. Test will result in maximum (i.e., best) total score of 53. Score will be graded by qualified staff into normative percentile score using provided chart. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in WETT Testing Score Over Time | Baseline up to 36 months | Taste assessment will be performed using taste strips (WETT). Four concentrations (4=lowest concentration, 1=highest concentration) will be used for each taste quality: sweet, sour, salty, bitter, and umami. Each test kit contains 53 taste strips distributed in 4 packs; and each taste strip is numbered (1 through 53). Participants will use each strip sequentially and record the flavor on a score card provided. The test will result in a maximum (that is, best) total score of 53. |
| Percentage of Time with Dysgeusia During the Prophylaxis Treatment Phase | Up to 12 months | Time with dysgeusia is defined as the accumulative days a participant had dysgeusia according to the total WETT score divided by the total days of talquetamab exposure. Taste assessment will be performed using taste strips (WETT). Four concentrations (4=lowest concentration, 1=highest concentration) will be used for each taste quality: sweet, sour, salty, bitter, and umami. Each test kit contains 53 taste strips distributed in 4 packs; and each taste strip is numbered (1 through 53). Participants will use each strip sequentially and record the flavor on a score card provided. The test will result in a maximum (that is, best) total score of 53. The score will be graded by a qualified site staff into a normative percentile score using a provided chart. |
| Percentage of Participants with Treatment-Emergent Oral Toxicities (Dysgeusia, Oral Mucositis, Dysphagia, and Xerostomia) During the Prophylaxis Treatment Phase | Up to 12 months | Oral toxicity including dysgeusia, oral mucositis, dysphagia, and xerostomia will be graded (including Grade 0 for dysgeusia) based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5.0. Severity has 5 grades based on CTCAE criteria: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening consequences; and Grade 5: Death. |
| Percentage of Participants with Treatment-Emergent Oral Toxicities (Dysgeusia, Oral Mucositis, Dysphagia, and Xerostomia) During the Study | Up to 30 days after the last dose of study treatment (that is, approximately up to 36 months) | Oral toxicity including dysgeusia, oral mucositis, dysphagia, and xerostomia will be graded (including Grade 0 for dysgeusia) based on NCI-CTCAE, Version 5.0. Severity has 5 grades based on CTCAE criteria: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening consequences; and Grade 5: Death. |
| Time to the First Onset of Treatment-Emergent Oral Toxicities (Dysgeusia, Oral Mucositis, Dysphagia, and Xerostomia) | Up to 36 months | Time to the first onset of treatment-emergent dysgeusia, oral mucositis, dysphagia, or xerostomia, will be reported. |
| Duration of Treatment-emergent Oral Toxicities (Dysgeusia, Oral Mucositis, Dysphagia, and Xerostomia) | Up to 36 months | Duration of treatment-emergent oral toxicities including dysgeusia, oral mucositis, dysphagia, and xerostomia will be reported in this outcome measure. |
| Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 items (EORTC-QLQ-C30) Domains Scores Over Time | From Baseline, up to 12 months (Cohorts A to E); up to 24 months (for Cohort F) | The EORTC-QLQ-C30 includes 30 items that make up 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, and nausea/vomiting), and 5 single symptom items (dyspnea, insomnia, appetite loss, constipation, and diarrhea) and a single impact item (financial difficulties). The recall period is 7 days, and responses are reported using verbal and numeric rating scales. The item and scale scores are transformed to a 0 to 100 scale. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning and a high score for the global health status represents high health related quality of life (HRQoL), but a high score for a symptom scale/item represents a high level of symptomatology/problems. |
| Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Oral Health (EORTC-QLQ-OH15) Domains Scores Over Time | From Baseline, up to 12 months (Cohorts A to E); up to 24 months (for Cohort F) | The EORTC module QLQ-OH15 is a 15-item, well-accepted, and validated assessment tool focusing on oral problems and quality of life. The recall period for symptoms is 7 days and response options include 'not at all', "a little', 'quite a bit', and 'very much'. All of the items' measures range in score from 0 to 100. A high score for the symptom items represents a high level of symptomatology or problems. |
| Percentage of Participants Reporting Oral Symptoms Using the Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) | Up to 12 months (Cohorts A to E); Up to 24 months (for Cohort F) | PRO-CTCAE is a patient-reported item custom survey used to evaluate symptomatic treatment-emergent adverse events in participants on cancer clinical trials. The PRO-CTCAE custom survey consists of 18 items. Responses are provided on a 5-point Likert scale that ranges from 0 to 4. The recall period for symptoms is 7 days. Higher scores indicating greater severity/impact. |
| Percentage of Participants Reporting Oral Symptoms Using the Short Xerostomia Inventory (SXI) Score | Up to 12 months (Cohorts A to E); Up to 24 months (for Cohort F) | SXI is a validated questionnaire that explores how the participant experiences dry mouth (xerostomia) with 5 questions extracted from the original XI. Respondents are asked to choose 1 of 5 responses ("1-Never; 2-Hardly ever; 3-Occasionally; 4-Fairly often; and 5-Very often") to specific statements referring to the preceding 4 weeks. Each individual's responses are scored and summed to give a single XI score. Higher scores represent more severe symptoms. |
| Percentage of Participants Reporting Oral Symptoms Using the Epstein Taste Survey (ETS) | Up to 12 months (Cohorts A to E); Up to 24 months (for Cohort F) | The Epstein Taste Survey (ETS) consists of 17 items PRO instrument, specific to taste and smell changes. The ETS was developed for use in participants with head and neck cancer. This instrument will be used to measure treatment-related symptoms associated with talquetamab. |
| Percentage of Participants Reporting Oral Symptoms Using the Scale of Subjective Total Taste Acuity (STTA) | Up to 12 months (Cohorts A to E); Up to 24 months (for Cohort F) | The STTA is a tool to assess the overall acuity of taste based on a 4-point scale, where 0 reflects no change and 4 represents almost complete loss of taste function. Higher score indicating severity. |
| Change from Baseline in Body Weight Over Time | From Baseline up to 36 months | Change from baseline in body weight will be reported. |
| Change from Baseline in Body Mass Index (BMI) Over Time | From Baseline up to 36 months | Change from baseline in BMI will be reported. |
| Percentage of Participants With Dose Reductions, Interruptions, and Discontinuations For Talquetamab and Ramantamig | Up to 12 months (Cohorts A to E); Up to 24 months (for Cohort F) | Percentage of participants with dose reductions, dose interruptions, and dose discontinuations will be reported. |
| Change from Baseline in Smell Identification Test Score | Baseline (Day 1 Cycle 1), Day 1 Cycle 2 (each cycle duration=28-days) | Smell identification testing will be performed using 4 booklets each containing 10 labels that will release a distinctive scent when scraped with a pencil. Participants will choose the appropriate scent from the associated options. The minimum possible score is a 0 and the maximum is a 40. A higher score indicates better smell/outcome. |
| Percentage of Participants With Overall Response Rate | Up to 36 months | Overall response rate is defined as the participants with a partial response (PR) or better according to the International Myeloma Working Group (IMWG) criteria. |
| Percentage of Participants With Complete Response (CR) or Better Response | Up to 36 months | CR or better response is defined as the participants who achieve a CR or better response according to the IMWG criteria. |
| Percentage of Participants With Very Good Partial Response (VGPR) or Better Response | Up to 36 months | VGPR or better response is defined as the percentage of participants who achieve a VGPR or better response according to the IMWG criteria. |
| Duration of Response (DOR) | Up to 36 months | Duration of response is defined as time from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria, or death due to any reason, whichever occurs first. |
| Time to Response (TTR) | Up to 36 months | Time to response is defined as the time between date of first dose of talquetamab or ramantamig and the first efficacy evaluation at which the participant has met all criteria for PR or better. |
| Progression-free Survival (PFS) | Up to 36 months | PFS is defined as the time from the date of first dose of talquetamab or ramantamig to the date of first documented disease progression, as defined in the IMWG criteria, or death due to any cause, whichever occurs first. |
| Number of Participants with Treatment-emergent Adverse Event (TEAEs) | Up to 36 months | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Any AE occurring at or after the initial administration of study treatment through the day of last dose plus 30 days, or if beyond 30 days from last dose but is study treatment-related, is considered to be treatment-emergent. |
Countries
Brazil, Netherlands, Puerto Rico, South Korea, Spain, United Kingdom, United States
Contacts
CONTACTStudy Contact
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed