Study for Frail Patients With Newly Diagnosed Multiple Myeloma Treated With Daratumumab With Teclistamab or Talquetamab.
- Conditions
- Multiple Myeloma (MM)
- Interventions
- Registration Number
- NCT07107529
- Lead Sponsor
- European Myeloma Network B.V.
- Brief Summary
This is a multicenter, open-label phase II study with 2 parallel cohorts for frail patients with newly diagnosed multiple myeloma treated with daratumumab in combination with teclistamab and talquetamab.
The main purpose of this study is to determine the progression free survival at 18 months in patients treated with teclistamab and daratumumab (Cohort 1) or talquetamab and daratumumab (Cohort 2).
- Detailed Description
This study will consist of 4 phases:
* Initial treatment phase where patients will receive fixed duration of Tec-Dara or Tal-Dara.
* TFI.
* Re-treatment phase, where patients with confirmed PD will continue treatment with Tec-Dara or Tal-Dara per their assignment in the initial treatment phase.
* Post-treatment follow-up phase.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 150
- Patient is ≥18 years of age and capable of giving informed consent and must sign an informed consent form (ICF), indicating that they understand the purpose of, and procedures required for, the study and is willing to participate in the study
- Newly diagnosed and treatment-naïve patients with a confirmed diagnosis of MM with measurable disease according to IMWG criteria
- Measurable disease defined as M-protein in the serum (≥1 g/dL) or serum free light chain assay ≥10 mg/dL [≥100 mg/L] and abnormal serum immunoglobulin kappa/lambda FLC ratio
- Frail according to the Simplified IMWG frailty index
- Have clinical laboratory values meeting defined range
- Patients of childbearing potential must agree to use adequate/highly effective contraception from the time of signing the informed consent form through 3 months after the last dose of study drug
-
Non-secretory MM or measurable disease by urine or plasmacytoma only
-
Central nervous system involvement of myeloma
-
Significant pulmonary dysfunction
-
Stroke, transient ischemic attack, or seizure within 6 months of eligibility
-
Evidence of active systemic viral, fungal, or bacterial infections, requiring systemic antimicrobial therapy
-
HIV and Hepatitis infections
-
Exclude for any of the following:
- Any history of malignancy other than MM which is considered at high risk of recurrence requiring treatment or a malignancy that has been treated with chemotherapy currently affecting bone marrow capacity.
- Any active malignancy (ie, progressing or requiring treatment change in the last 24 months) other than multiple myeloma.
-
Active autoimmune disease requiring systemic immunosuppressive therapy within 6 months before eligibility
-
Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study treatment or its excipients (refer to IB and most recently applicable RSI)
-
Extensive radiotherapy within 14 days or focal radiation only within 7 days of eligibility
-
Current or active therapy for multiple myeloma or received a cumulative dose corticosteroids equivalent to >40 mg dexamethasone within the 14 days prior to C1D1
-
Received a live attenuated vaccine ≤4 weeks before eligibility. Non-live vaccines or non-replicating authorized for emergency use (eg, COVID-19) are allowed
-
Received a strong CYP3A4 inducer or use of St. John's wort ≤5 half-lives prior to dosing
-
Patient had major surgery or significant traumatic injury within 2 weeks prior to eligibility. Kyphoplasty or Vertebroplasty is not considered major surgery
-
Have received an investigational drug (including investigation vaccines) or used an invasive investigational medical device <4 week or 5 PK half-lives, before eligibility or is currently enrolled in an interventional investigational study except if only long-term survival data are collected
-
Concurrent medical or psychiatric condition or disease (eg, uncontrolled diabetes, alcohol or drug abuse, severe dementia or altered mental status), that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participation in the study
-
Any other issue that would impair the ability of the patient to receive or tolerate the planned treatment at the investigational site, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (eg,, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1 Teclistamab Tec-Dara Cohort 1 Daratumumab Tec-Dara Cohort 2 Talquetamab Tal-Dara Cohort 2 Daratumumab Tal-Dara
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) per IMWG criteria 18 months defined as the time from the date of randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier, where disease progression is determined per IMWG criteria.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) 9 years Measured from the date of from randomization to the date the subject's death.
Minimal Residual Disease (MRD) negativity rate 18 months Minimal Residual Disease (MRD) negative as determined by NGF at 10\^-5 sensitivity level per International Myeloma Working Group (IMWG) criteria.
Minimal Residual Disease (MRD) negative CR 18 months Minimal Residual Disease (MRD) negative Complete Remission (CR) at the end of fixed treatment duration status as determined by NGF at 10\^-5 sensitivity level and who also achieve CR or better per International Myeloma Working Group (IMWG) criteria.
Sustained Minimal Residual Disease (MRD) negative CR 9 years Sustained MRD-negative CR is defined as patients with CR or better who sustain MRD-negative status, as determined NGF at 10\^-5.
IMWG best response 18 months To evaluate the proportion of IMWG best response achieved by a patient during the study. Subject will be classified as Not Evaluable (NE) if they will not have any evaluable response assessment.
Time to response 9 years Time from the date of randomization to the date of first documentation of a confirmed response (partial response) as per IMWG response criteria, for patients who have PR or better as their best response.
Time to best response 9 years Time from the date of randomization to the date of first best response as per IMWG response criteria.
Event free survival (EFS) 9 years Time from the date of randomization to the date of first documented disease progression, as defined in the IMWG criteria, or death due to any cause or treatment discontinuation due to toxicity, whichever occurs first.
Progression Free Survival 2 (PFS2) 9 years Time from the randomization date to the date of event, which is defined as death from any cause or progression disease on the next line of therapy, whichever occurs first.
Time to Next Treatment (TNT) 9 years Time from the randomization date to the date of event, which is defined as the start of the next line of therapy or death from any cause, whichever occurs first.
Adverse Events 9 years Incidence and severity of Adverse Events during initial therapy, Treatment-Free-Interval (TFI) and after restarting therapy.
Discontinuation 9 years Discontinuation rate and cause due to treatment related toxicity during initial therapy and after restarting therapy, including overall discontinuation rate, discontinuation rate of daratumumab, teclistamab and talquetamab.
Change from Baseline in Health-Related Quality of Life as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score Up to 9 years The EORTC QLQ-C30 includes 30 items in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single symptom items.
Change from Baseline in Health-Related Quality of Life as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Myeloma 20 (EORTC-MY-20) Scale Score Up to 9 years The EORTC-QLQ-MY20 is a specialised tool designed to assess the quality of life in myeloma patients.
Change from Baseline in Health-Related Quality of Life as Assessed by Activities of Daily Living (ADL) questionnaire Up to 9 years The ADL questionnaire assesses functional status by measuring independence in six daily activities.
Change from Baseline in Health-Related Quality of Life as Assessed by Instrumental Activities of Daily Living (IADL) questionnaire Up to 9 years The IADL assesses instrumental activities of daily living, including telephone use, laundry, shopping, food preparation, and mode of transportation.
Change from Baseline in Health-Related Quality of Life as Assessed by Scale of Subjective Total Taste Acuity (STTA) Up to 9 years The STTA scale assesses the taste acuity during treatment.
Change from Baseline in the geriatric assessment as Assessed by Geriatric Depression Scale (GDS) Up to 9 years The GDS scale assesses the depressive symptoms in frail elderly patients.
Change from Baseline in the geriatric assessment as Assessed by Mini Nutritional Assessment (MNA) questionnaire Up to 9 years The MNA is a validated nutrition screening and assessment tool that can identify geriatric patients age 65 and above who are malnourished or at risk of malnutrition.
Change from Baseline in the geriatric assessment as Assessed by Mini-Mental State Examination (MMSE) Up to 9 years The MMSE is an 11-question tool to assess mental status, testing five cognitive areas.
Change from Baseline in the geriatric assessment as Assessed by Geriatric Assessment in Hematology (GAH) scale Up to 9 years The GAH scale predicts treatment tolerability in older patients diagnosed with hematological malignancies.