Study for Frail Patients With Newly Diagnosed Multiple Myeloma Treated With Daratumumab With Teclistamab or Talquetamab.

Phase 2RecruitingNCT07107529

European Myeloma Network B.V.150 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

150

Conditions

Multiple Myeloma (MM)

Interventions

TeclistamabDRUG

Teclistamab will be administered via a subcutaneous injection (SC), fixed duration and will be retreated until disease progression or intolerable toxicity.

TalquetamabDRUG

Talquetamab will be administered via a subcutaneous injection (SC), fixed duration and will be retreated until disease progression or intolerable toxicity.

DaratumumabDRUG

Dartumumab will be administered via a subcutaneous injection (SC), fixed duration and will be retreated until disease progression or intolerable toxicity.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. 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 2. Newly diagnosed and treatment-naïve patients with a confirmed diagnosis of MM with measurable disease according to IMWG criteria 3. 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 4. Frail according to the Simplified IMWG frailty index 5. Have clinical laboratory values meeting defined range 6. 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 Exclusion Criteria: 1. Non-secretory MM or measurable disease by urine or plasmacytoma only 2. Central nervous system involvement of myeloma 3. Significant pulmonary dysfunction 4. Stroke, transient ischemic attack, or seizure within 6 months of eligibility 5. Evidence of active systemic viral, fungal, or bacterial infections, requiring systemic antimicrobial therapy 6. HIV and Hepatitis infections 7. Exclude for any of the following: 1. 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. 2. Any active malignancy (ie, progressing or requiring treatment change in the last 24 months) other than multiple myeloma. 8. Active autoimmune disease requiring systemic immunosuppressive therapy within 6 months before eligibility 9. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study treatment or its excipients (refer to IB and most recently applicable RSI) 10. Extensive radiotherapy within 14 days or focal radiation only within 7 days of eligibility 11. 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 12. Received a live attenuated vaccine ≤4 weeks before eligibility. Non-live vaccines or non-replicating authorized for emergency use (eg, COVID-19) are allowed 13. Received a strong CYP3A4 inducer or use of St. John's wort ≤5 half-lives prior to dosing 14. Patient had major surgery or significant traumatic injury within 2 weeks prior to eligibility. Kyphoplasty or Vertebroplasty is not considered major surgery 15. 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 16. 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 17. 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

Locations (29)

Outcomes

Primary Outcomes

Progression Free Survival (PFS) per IMWG criteria

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.

Time frame: 18 months

Secondary Outcomes

Overall Survival (OS)

Measured from the date of from randomization to the date the subject's death.

Time frame: 9 years

Minimal Residual Disease (MRD) negativity rate

Minimal Residual Disease (MRD) negative as determined by NGF at 10\^-5 sensitivity level per International Myeloma Working Group (IMWG) criteria.

Time frame: 18 months

Minimal Residual Disease (MRD) negative CR

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.

Time frame: 18 months

Sustained Minimal Residual Disease (MRD) negative CR

Sustained MRD-negative CR is defined as patients with CR or better who sustain MRD-negative status, as determined NGF at 10\^-5.

Time frame: 9 years

IMWG best response

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 frame: 18 months

Time to response

Central Contacts

Clinical Trial Office

CONTACT

+390110243236 amministrazione@emnresearch.it

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

IT-Ascoli Piceno-Ospedale Mazzoni [01-016]

Ascoli Piceno, Italy

RECRUITING

IT-Bari-A.O.U. Consorziale Policlinico - Medicina Interna [01-018]

Bari, Italy

NOT_YET_RECRUITING

IT-Bergamo-A.O. Papa Giovanni XXIII [01-003]

Bergamo, Italy

NOT_YET_RECRUITING

IT-Bologna-A.O.U. di Bologna - Policlinico S. Orsola Malpighi [01-004]

Bologna, Italy

NOT_YET_RECRUITING

IT-Bolzano-Ospedale di Bolzano - Azienda Sanitaria dell'Alto Adige [01-021]

Bolzano, Italy

NOT_YET_RECRUITING

IT-Como-Ospedale Classificato Valduce [01-104]

Como, Italy

RECRUITING

IT-Milano-Fondazione IRCCS Ca' Grande Ospedale Maggiore Policlinico [01-039]

Milan, Italy

NOT_YET_RECRUITING

IT-Milano-Ospedale S. Carlo Borromeo [01-105]

Milan, Italy

RECRUITING

IT-Novara-A.O.U. Maggiore della Carità [01-010]

Novara, Italy

RECRUITING

IT-Pescara-Azienda USL di Pescara P.O. dello Spirito Santo [01-053]

Pescara, Italy

RECRUITING

...and 19 more locations

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

Time from the date of randomization to the date of first best response as per IMWG response criteria.

Time frame: 9 years

Event free survival (EFS)

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.

Time frame: 9 years

Progression Free Survival 2 (PFS2)

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 frame: 9 years

Time to Next Treatment (TNT)

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.

Time frame: 9 years

Adverse Events

Incidence and severity of Adverse Events during initial therapy, Treatment-Free-Interval (TFI) and after restarting therapy.

Time frame: 9 years

Discontinuation

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.

Time frame: 9 years

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

The EORTC QLQ-C30 includes 30 items in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single symptom items. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.

Time frame: Up to 9 years

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

The EORTC-QLQ-MY20 is a specialised tool designed to assess the quality of life in myeloma patients. Scores are linearly transformed to a 0-100 scale, where higher scores on the symptom scales indicate worse outcomes.

Time frame: Up to 9 years

Change from Baseline in Health-Related Quality of Life as Assessed by Activities of Daily Living (ADL) questionnaire

The ADL questionnaire assesses functional status by measuring independence in six daily activities. The ADL scale is scored from 0 to 8, where higher scores indicate greater independence with daily activities.

Time frame: Up to 9 years

Change from Baseline in Health-Related Quality of Life as Assessed by Instrumental Activities of Daily Living (IADL) questionnaire

The IADL assesses instrumental activities of daily living, including telephone use, laundry, shopping, food preparation, and mode of transportation. The IADL scale is scored from 0 to 8, with higher scores indicating greater independence.

Time frame: Up to 9 years

Change from Baseline in Health-Related Quality of Life as Assessed by Scale of Subjective Total Taste Acuity (STTA)

The STTA scale assesses the taste acuity during treatment. The STTA scale is scored from 0 to 4, where 4 indicates almost complete loss of taste acuity.

Time frame: Up to 9 years

Change from Baseline in the geriatric assessment as Assessed by Geriatric Depression Scale (GDS)

The GDS scale assesses the depressive symptoms in frail elderly patients. The GDS scale is scored from 0 to 15. Score 1 point for each bolded answer. A score of 5 or more suggests depression.

Time frame: Up to 9 years

Change from Baseline in the geriatric assessment as Assessed by Mini Nutritional Assessment (MNA) questionnaire

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. The MNA scale is scored from 1 to 30. A higher score represents good nutrition, a score less then 17 represents malnutrition.

Time frame: Up to 9 years

Change from Baseline in the geriatric assessment as Assessed by Mini-Mental State Examination (MMSE)

The MMSE is an 11-question tool to assess mental status, testing five cognitive areas. The MMSE scale is scored from 1 to 30. A higher score represents good mental state.

Time frame: Up to 9 years

Change from Baseline in the geriatric assessment as Assessed by Geriatric Assessment in Hematology (GAH) scale

The GAH scale predicts treatment tolerability in older patients diagnosed with hematological malignancies. The 30-item GAH scale was designed through a multi-step process to cover 8 relevant dimensions. Higher scores indicate a more frail or vulnerable patient.

Time frame: Up to 9 years