A Study of Teclistamab in Combination With Daratumumab Subcutaneously (SC) (Tec-Dara) Versus Daratumumab SC, Pomalidomide, and Dexamethasone (DPd) or Daratumumab SC, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT05083169
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to compare the efficacy of teclistamab daratumumab (Tec-Dara) with daratumumab subcutaneously (SC) in combination with pomalidomide and dexamethasone (DPd) or daratumumab SC in combination with bortezomib and dexamethasone (DVd).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 587
- Documented multiple myeloma as defined by the criteria: a. multiple myeloma diagnosis according to the 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 gram per deciliter (g/dL); or 2) urine M-protein level >=200 milligrams (mg)/24 hours; or 3) serum immunoglobulin free light chain >=10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
- Received 1 to 3 prior line(s) of antimyeloma therapy including a proteasome inhibitor (PI) and lenalidomide; a. participants who have received only 1 line of prior line of antimyeloma therapy must be lenalidomide refractory. Stable disease or progression on or within 60 days of the last dose of lenalidomide given as maintenance will meet this criterion
- 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 (ECOG) performance status score of 0, 1, or 2 at screening and prior to the start of administration of study treatment
- Have clinical laboratory values within the specified range
-
Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients. Additional exclusion criteria pertaining to specific study drugs include:
- A participant is not eligible to receive daratumumab subcutaneous (SC) in combination with pomalidomide and dexamethasone (DPd) as control therapy if any of the following are present: 1) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to pomalidomide, 2) Disease that is considered refractory to pomalidomide per IMWG,
- A participant is not eligible to receive daratumumab SC in combination with bortezomib and dexamethasone (DVd) as control therapy if any of the following are present: 1) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to bortezomib, 2) Grade 1 peripheral neuropathy with pain or Grade >= 2 peripheral neuropathy as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, 3) Disease that is considered refractory to bortezomib per IMWG, 4) Received a strong cytochromes P450 (CYP3A4) inducer within 5 half-lives prior to randomization
-
Received any prior B cell maturation antigen (BCMA)-directed therapy
-
Has disease that is considered refractory to an anti-cluster of differentiation 38 (CD38) monoclonal antibody per IMWG
-
Received a cumulative dose of corticosteroids equivalent to >=140 mg of prednisone within 14 days before randomization
-
Received a live, attenuated vaccine within 4 weeks before randomization
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Plasma cell leukemia at the time of screening, Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary amyloid light chain amyloidosis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Teclistamab-daratumumab (Tec-Dara) Daratumumab Participants will receive teclistamab and daratumumab by subcutaneous (SC) injection. Step-up doses of teclistamab will be given prior to the first full dose. Arm A: Teclistamab-daratumumab (Tec-Dara) Teclistamab Participants will receive teclistamab and daratumumab by subcutaneous (SC) injection. Step-up doses of teclistamab will be given prior to the first full dose. Arm B: DPd or DVd Daratumumab Participants will be randomized either to daratumumab, pomalidomide, dexamethasone (DPd) treatment to receive daratumumab SC injection; pomalidomide orally; dexamethasone orally or intravenously, or to Daratumumab, Bortezomib, Dexamethasone (DVd) treatment to receive daratumumab SC injection; bortezomib SC injection, and dexamethasone orally or intravenously. Arm B: DPd or DVd Pomalidomide Participants will be randomized either to daratumumab, pomalidomide, dexamethasone (DPd) treatment to receive daratumumab SC injection; pomalidomide orally; dexamethasone orally or intravenously, or to Daratumumab, Bortezomib, Dexamethasone (DVd) treatment to receive daratumumab SC injection; bortezomib SC injection, and dexamethasone orally or intravenously. Arm B: DPd or DVd Dexamethasone Participants will be randomized either to daratumumab, pomalidomide, dexamethasone (DPd) treatment to receive daratumumab SC injection; pomalidomide orally; dexamethasone orally or intravenously, or to Daratumumab, Bortezomib, Dexamethasone (DVd) treatment to receive daratumumab SC injection; bortezomib SC injection, and dexamethasone orally or intravenously. Arm B: DPd or DVd Bortezomib Participants will be randomized either to daratumumab, pomalidomide, dexamethasone (DPd) treatment to receive daratumumab SC injection; pomalidomide orally; dexamethasone orally or intravenously, or to Daratumumab, Bortezomib, Dexamethasone (DVd) treatment to receive daratumumab SC injection; bortezomib SC injection, and dexamethasone orally or intravenously.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) Up to 5 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) criteria, or death due to any cause, whichever occurs first.
- Secondary Outcome Measures
Name Time Method Very Good Partial Response (VGPR) or Better Up to 5 years VGPR or better is defined as participants who achieve a VGPR or better response per IMWG criteria.
Complete Response (CR) or Better Up to 5 years CR or better is defined as participants who achieve a CR or better response per IMWG criteria.
Minimal Residual Disease (MRD)-negativity Up to 5 years MRD-negativity is defined as participants who achieve MRD negativity at a threshold of 10\^-5 at any timepoint after the date of randomization and before disease progression or start of subsequent antimyeloma therapy.
Progression Free Survival on Next-line Therapy (PFS2) Up to 5 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 5 years OS is measured from the date of randomization to the date of the participant's death.
Time to Next Treatment (TTNT) Up to 5 years TTNT is defined as the interval time from randomization to the start of subsequent antimyeloma treatment.
Duration of Response Up to 5 years Duration of response will be calculated among responders (with a PR or better response) from 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 response criteria, or death due to any cause, whichever occurs first.
Number of Participants with Adverse Events (AEs) by Severity Up to 5 years Number of participants with AEs by Severity will be reported.
Serum Concentration of Teclistamab Up to 5 years Serum samples will be analyzed to determine concentrations of teclistamab using a validated, specific, and sensitive method.
Number of Participants with Anti-drug Antibodies (ADAs) to Teclistamab and Daratumumab Up to 5 years Number of participants with ADAs to teclistamab and daratumumab will be reported.
Time to Worsening of Symptoms Up to 5 years Time to worsening is measured as the interval from the date of randomization to the start date of meaningful change.
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 5 years The EORTC-QLQ-C30 Version 3 includes 30 items in 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 responses are reported using a 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. 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 5 years 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 Measurement Information System Short Form v2.0 - Physical Function 8c (PROMIS PF 8c) Baseline up to 5 years The PROMIS-SD is used to assess self-reported perceptions of sleep quality, sleep depth and restoration associated with sleep. The 8-item short form will be used in this study, in which responses are scored 1 to 5 for each item. Higher overall score indicates more sleep disturbance.
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 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.
Overall Response (Partial Response [PR] or Better) Up to 5 years Overall response (PR or better) is defined as participants who have a PR or better per IMWG criteria.
Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L) Baseline up to 5 years 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).
Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Patient Global Impression - Severity (PGI-S) Baseline up to 5 years The PGIS contains 2 questions on how the participant would currently rate severity of symptoms and impacts with a 7-day recall period. The response options are presented as a 5-point verbal rating scale from 1="none" to 5="very severe."
PFS in Participants with High-risk Molecular Features Up to 5 years PFS in participants with high-risk molecular features will be reported.
Depth of Response in Participants in High-risk Molecular Features Up to 5 years Depth of response in participants in high-risk molecular features will be reported.
Trial Locations
- Locations (174)
University of Alabama Birmingham
🇺🇸Birmingham, Alabama, United States
City of Hope
🇺🇸Duarte, California, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Emory University Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Ascension Providence Hospital
🇺🇸Southfield, Michigan, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
West Penn Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Scroll for more (164 remaining)University of Alabama Birmingham🇺🇸Birmingham, Alabama, United States