Clinical trial NCT06682156: Conversion to Carfilzomib Therapy in Bortezomib Intolerant Newly Diagnosed Multiple Myeloma(NDMM) Patients
Official title: Clinical Outcome of Multiple Myeloma Patients Switching to Carfilzomib-based Regimens After Prior Bortezomib-based First-line Therapy Intolerant, a Real-world, Single-arm, Prospective Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Newly Diagnosed Multiple Myeloma
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2024-11-12
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Newly diagnosed multiple myeloma patients who develop toxicities associated with bortezomib therapy evaluated by the investigator, including the presence of Grade 1 with pain or Grade 2 peripheral neuropathy (PN), Grade 3 hepatic impairment, Grade 3 diarrhea, and any other Grade 3 non-hematologic adverse events

Brief summary: This is an open-label, single-arm, prospective study conducted in real-world clinical practice. It aims to evaluate the efficacy and safety in Chinese patients with newly diagnosed multiple myeloma who switch to carfilzomib-based regimens after bortezomib-based triple-drug regimen intolerance happens.

Detailed description: This is an open-label, single-arm, prospective study conducted in real-world clinical practice. Chinese patients with newly diagnosed multiple myeloma will be enrolled if they switch to carfilzomib-based regimens after bortezomib-based triple-drug regimen intolerance happens.

Induction and consolidation therapy will be 6-8cycles. 6 cycles for transplant recipients and 8 cycles for non-transplant recipients. Maintenance therapy will continue until progression.

It aims to evaluate the efficacy and safety of carfilzomib based therapy in Chinese NDMM patients with intolerance to bortezomib. The primary endpoint is the rate of 2-year pFS and secondary endpoints are the rate of ORR,sCR/CR,VGPR,PR, the rate and duration of MRD, the rate of 2-year OS and safety.

Eligibility criteria: Inclusion Criteria:

1. ≥ 18 years of age
2. Diagnosed with multiple myeloma according to IMWG criteria.
3. Patients who have received only first-line bortezomib-based triple therapy, including bortezomib/lenalidomide/dexamethasone (VRD), bortezomib/thalidomide/dexamethasone (VTD）,bortezomib/ cyclophosphamide/dexamethasone (VCD), and bortezomib/adriamycin//dexamethasone (PAD).
4. Eastern cooperative oncology group(ECOG) score 0-2
5. Patients who develop toxicities associated with bortezomib therapy evaluated by the investigator, including the presence of Grade 1 with pain or Grade 2 peripheral neuropathy (PN), Grade 3 hepatic impairment, Grade 3 diarrhea, and any other Grade 3 non-hematologic adverse events and resulting in bortezomib dose reduction or discontinuation.
6. Patients who agree to and sign informed consents to participate in this study.

Exclusion Criteria:

1. Patients currently participating in other interventional clinical studies (except those currently participating in non-interventional observational studies)
2. Patients who have received prior carfilzomib treatment or participated in carfilzomib associated studies (with or without carfilzomib treatment).
3. Patients with a primary diagnosis of MM combined with plasma cell leukemia (peripheral blood monoclonal plasma cells ≥5% of the total number of differentiated mature leukocytes)
4. Patients who have not fully recovered from the reversible effects of prior chemotherapy (i.e., \<= grade 1 toxicity).
5. Patients with other malignancies diagnosed prior to the MM diagnosis, excluding squamous and basal cell carcinomas of the skin, and carcinoma in situ of the cervix or breast, which can be cured within 3 years with minimal risk of recurrence.
6. Patients with an active systemic infection, active hepatitis B or C virus infection, or known positive test results for human immunodeficiency virus.
7. Evidence of current uncontrolled cardiovascular disease, including hypertension, arrhythmias (prolonged QT interval, ventricular tachycardia, ventricular flutter, ventricular fibrillation, frequent ventricular premature beats (24-hour premature loading of ≥15% of the total number of beats), grade Ⅲ atrioventricular block, and a heart rate of \<30-40 bpm congestive heart failure, unstable angina, or myocardial infarction in the past 3 months,. New York Heart Association (NYHA) class III and IV heart failure. left ventricle ejection fraction（LVEF） \<40% on cardiac ultrasound.
8. Participants with known chronic obstructive pulmonary disease (COPD) (defined as forced expiratory volume in 1 second \[FEV1\] \<50% of predicted normal value), persistent asthma, or a history of asthma within the past 2 years (controlled intermittent asthma or mild persistent asthma that is allowed). Participants with known or suspected COPD must undergo FEV1 testing during screening.
9. Inability to comply with protocol/procedure.
10. Patients with hypersensitivity to the active ingredient or excipients of carfilzomib.
11. Pregnant or lactating women

Primary outcomes:
measure: Outcome of peripheral neuropathy
timeFrame: from enrollment to 2 years
Secondary outcomes:
measure: ORR
timeFrame: from enrollment to 2 years
measure: sCR/CR rate
timeFrame: from enrollment to 2 years
measure: PR rate
timeFrame: from enrollment to 2 years
measure: VGPR rate
timeFrame: from enrollment to 2 years
measure: MRD negativity rate
timeFrame: from enrollment to 2 years
measure: AE rate
timeFrame: from enrollment to 2 years
measure: 2-year OS rate
timeFrame: from enrollment to 2 years
measure: Duration of MRD negativity
timeFrame: from enrollment to 2 years
measure: 2-year PFS rate
timeFrame: from enrollment to 2 years
Other outcomes:
Locations:
city: Suzhou
country: China
facility: Lingzhi Yan
state: Jiangsu
Study officials:
References: