A Study Comparing Teclistamab Monotherapy versus Pomalidomide, Bortezomib, Dexamethasone (PVd) or Carfilzomib, Dexamethasone (Kd) in Participants with Relapsed or Refractory Multiple Myeloma

JRCT ID: jRCT2041220125

Registered date:22/01/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Relapsed or Refractory Multiple Myeloma
• Date of first enrollment: 26/05/2023
• Target sample size: 590
• Countries of recruitment: Australia,Japan,Belgium,Japan,Brazil,Japan,Czechia,Japan,Germany,Japan,Denmark,Japan,Spain,Japan,France,Japan,Greece,Japan,India,Japan,Israel,Japan,Italy,Japan,Malaysia,Japan,Netherlands,Japan,Poland,Japan,Sweden,Japan
• Study type: Interventional

Intervention(s)

Teclistamab: Participants will receive teclistamab monotherapy.Teclistamab will be administered subcutaneously.
Pomalidomide, Bortezomib and Dexamethasone (PVd) or Carfilzomib and Dexamethasone (Kd): Participants will receive either PVd or Kd based on principal investigator's choice.
Pomalidomide: Pomalidomide will be administered orally.
Bortezomib: Bortezomib will be administered subcutaneously.
Dexamethasone: Dexamethasone will be administered orally in PVd and intravenously or orally in Kd.
Carfilzomib: Carfilzomib will be administered intravenously.

Outcome(s)

Primary Outcome

Progression-free Survival (PFS)
Up to 9 years
PFS is defined as the time from the date of randomization to the date of first documented disease progression, as defined in the International myeloma working group (IMWG) 2016 response criteria, or death due to any cause, whichever occurs first.

Secondary Outcome

Overall Response (Partial Response [PR] or Better)
Up to 9 years
Overall response (PR or better) is defined as participants who have a PR or better prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 criteria.

Very Good Partial Response (VGPR) or Better Response
Up to 9 years
VGPR or better (Stringent Complete Response [sCR]+Complete Response [CR]+VGPR) is defined as participants who achieve a VGPR or better response prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 criteria.

Complete Response (CR) or Better Response
Up to 9 years
CR or better response is defined as participants who achieve a CR or better response prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 criteria.

Duration of Response (DOR)
Up to 9 years
DOR is defined as the time interval between the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG 2016 response criteria or death due to any cause, whichever occurs first.

Time to Next Treatment (TTNT)
Up to 9 years
TTNT is defined as the time from randomization to the start of subsequent antimyeloma treatment.

Progression-free Survival on Next-line Therapy (PFS2)
Up to 9 years
PFS2 is defined as the time interval between the date of randomization and date of event, which is defined as progressive disease as assessed by investigator on the first subsequent line of antimyeloma therapy, or death from any cause, whichever occurs first.

Overall Survival (OS)
Up to 9 years
OS is defined as the time from the date of randomization to the date of the participant's death due to any cause.

Number of Participants with Adverse Events (AEs) by Severity
Up to 9 years
Number of participants with AEs by Severity will be reported.

Number of Participants with Serious Adverse Events (SAEs) by Severity
Up to 9 years
Number of participants with SAEs by Severity will be reported.

Number of Participants with Abnormal Laboratory Results
Up to 9 years
Number of participants with abnormal laboratory results (such as hematology and chemistry) will be reported.

Serum Concentrations of Teclistamab
Up to 9 years
Serum concentrations of teclistamab will be reported.

Number of Participants with Anti-drug Antibodies (ADAs) to Teclistamab
Up to 9 years
Number of participants with ADAs to teclistamab will be reported.

Change from Baseline in Symptoms, Functioning, and Overall Health-related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30)
Baseline up to 9 years
Change from baseline in symptoms, functioning, and overall HRQoL assessed by EORTC QLQ-C30 score version 3 will be reported. The EORTC- QLQ-C30 Version 3 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 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The item and scale scores are transformed to a 0 to 100 scale. A high scale score represents a higher response level. Thus, 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 HRQoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.

Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) Scale Score
Baseline up to 9 years
Change from baseline in symptoms, functioning, and overall HRQoL assessed by MySIm-Q will be reported. The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items resulting in a symptom subscale and an impact subscale. The recall period is the 'past 7 days', and responses are reported on a 5-point verbal rating scale.

Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Baseline up to 6 months
Change from baseline in symptoms, functioning, and overall HRQoL assessed by PRO-CTCAE will be reported. The National Cancer Institute's (NCI's) PRO-CTCAE is an item library of common adverse events experienced by people with cancer that are appropriate for self-reporting of treatment tolerability. Each symptom selected for inclusion can be rated by up to 3 attributes characterizing the presence/frequency, severity, and/or interference of the AEs. It ranges from 0 to 4 with higher scores indicating higher frequency or greater severity/impact.

Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L)
Baseline up to 9 years
Change from baseline in symptoms, functioning, and overall HRQoL assessed by EQ-5D-5L will be reported. The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression plus a visual analog scale rating 'health today' with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).

Time to Worsening in Symptoms, Functioning, and Overall HRQoL
Up to 9 years
Time to worsening in symptoms, functioning, and overall HRQoL will be measured as the interval from the date of randomization to the start date of meaningful change.

PFS in Participants in High-risk Molecular Features
Up to 9 years
PFS in participants in high-risk molecular features will be reported. PFS is defined as the time from the date of randomization to the date of first documented disease progression, as defined in the IMWG 2016 response criteria, or death due to any cause, whichever occurs first.

Depth of Response in Participants in High-risk Molecular Features
Up to 9 years
Depth of response in participants in high-risk molecular features will be reported.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Documented diagnosis of multiple myeloma as defined by the criteria below:
(a)Multiple myeloma diagnosis according to International Myeloma Working Group (IMWG) diagnostic criteria (b) Measurable disease at screening as defined by any of the following: (1) Serum M-protein level greater than or equal to (>=)0.5 grams per deciliter (g/dL) (central laboratory); or (2) Urine M-protein level >=200 milligrams (mg)/24 hours (central laboratory); or (3) Serum immunoglobulin free light chain >=10 milligrams per deciliter (mg/dL) (central laboratory) and abnormal serum immunoglobulin kappa lambda free light chain ratio
- Received 1 to 3 prior lines of antimyeloma therapy including a minimum of 2 consecutive cycles of an anti- cluster of differentiation 38 (CD38) monoclonal antibody at the approved dosing regimen in any prior line and 2 consecutive cycles of lenalidomide in any prior line
- Documented evidence of progressive disease or failure to achieve a response to last line of therapy based on investigator's determination of response by International myeloma working group (IMWG) criteria
- Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2
- A female participant must agree not to be pregnant, breast-feeding, or plan to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment
- Must be willing and able to adhere to the lifestyle restrictions specified in this protocol

Exclude criteria

- Received any prior B cell maturation antigen (BCMA)-directed therapy
-A participant is not eligible to receive PVd as control therapy if any of the following are present: (1) Received prior pomalidomide therapy, (2) Does not meet criteria for bortezomib retreatment (3) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to pomalidomide or bortezomib, (4) Grade 1 peripheral neuropathy with pain or Grade greater than or equal to (>=) 2 peripheral neuropathy as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, (5) Received a strong cytochrome P (CYP) 3A4 inducer within 5 half-lives prior to randomization; A participant is not eligible to receive Kd as control therapy if any of the following are present:(1) Received prior carfilzomib therapy, (2) Uncontrolled hypertension, defined as an average systolic blood pressure greater than (>)159 millimeters of mercury (mmHg) or diastolic blood pressure >99 mmHg despite optimal treatment (3) Grade 2 peripheral neuropathy with pain or Grade >=3 peripheral neuropathy as defined by NCI-CTCAE Version 5.0, (4) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to carfilzomib (intolerance defined as prior therapy discontinued due to any adverse event [AE] related to carfilzomib)
- Central nervous system (CNS) involvement or clinical signs of meningeal involvement of multiple myeloma.
- Received a live, attenuated vaccine within 4 weeks before randomization
- Plasma cell leukemia at the time of screening, Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, M-protein (POEMS) syndrome and skin changes, or primary amyloid light chain amyloidosis
- Received a maximum cumulative dose of corticosteroids of >=140 mg of prednisone or equivalent within 14 days prior to randomization

Related Information

• Primary Sponsor: Nishikawa Kazuko
• Secondary ID(s): NCT05572515