Clinical trial NCT06497738: A Prospective Study Comparing DRd With VRd-lite in Elderly Newly Diagnosed Multiple Myeloma
Official title: A Prospective, Multi-center, Open-label, Cohort Study to Compare Daratumumab-Lenalidomide-Dexamethasone (DRd) With Modified Bortezomib-Lenalidomide-Dexamethasone (VRd-lite) in Elderly Newly Diagnosed Multiple Myeloma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Multiple Myeloma
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2024-07-12
Enrollment: 112
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 1. Age ≥ 65 years old
2. Newly diagnosed Multiple myeloma patients

Brief summary: The purpose of the study is to compare the efficacy and safety of daratumumab, lenalidomide and dexamethasone (DRd) to that of modified bortezomib, lenalidomide and dexamethasone (VRd-lite), in terms of progression-free survival and minimal residual disease negativity rate in elderly participants with newly diagnosed multiple myeloma.

Detailed description: This is a prospective, open-label, multicentered cohort study. This study will evaluate elderly participants with newly diagnosed multiple myeloma (MM) for whom hematopoietic stem cell transplant is not planned as initial therapy. All the eligible participants can be free to choose to receive either daratumumab lenalidomide and dexamethasone (DRd) or modified bortezomib lenalidomide and dexamethasone (VRd-lite). Daratumumab (16 milligram per kilogram \[mg/kg\]) will be administered weekly for first 8 weeks (Cycles 1 to 2) of treatment and then every other week for 16 weeks (Cycles 3 to 6), then every 4 weeks (Cycle 7 to 8). Bortezomib will be administered subcutaneously 1.3 mg/m\^2 weekly of each 28-day cycle for Cycles 1-8. Lenalidomide will be administered at a dose of 25 mg orally on Days 1 through 21 of each 28-day cycle, and dexamethasone will be administered at a dose of 20 mg twice a week for both treatment arms. Participants in both treatment arms will continue at least lenalidomide maintenance until disease progression or unacceptable toxicity.The primary endpoint will be progression-free survival (PFS) and percentage of participants with Negative Minimal Residual Disease (MRD). Participant safety will be assessed throughout the study.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 65 years old
2. Newly diagnosed Multiple myeloma patients with measurable disease. Diagnosis of multiple myeloma as documented per International Myeloma Working Group (IMWG) criteria：Monoclonal plasma cells in the bone marrow greater than or equal to (\>=)10 percentage (%) or presence of a biopsy proven plasmacytoma and documented multiple myeloma satisfying at least one of the calcium, renal, anemia, bone (CRAB) criteria or SLiM. CRAB criteria: Hypercalcemia: serum calcium greater than (\>) 0.25 millimoles per liter (mmol/L) (\>1 milligram per deciliter \[mg/dL\]) higher than upper limit of normal (ULN) or \>2.75 mmol/L (\>11 mg/dL); Renal insufficiency: creatinine clearance less than (\<) 40 milliliter per minute (mL/min) or serum creatinine \>177 micro millimoles per liter (umol/L) (\>2 mg/dL); Anemia: hemoglobin \>2 g/dL below the lower limit of normal or hemoglobin \<10 g/dL; Bone lesions: one or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)-CT. SLiM: Clonal bone marrow plasma cell percentage \>=60%; Involved: uninvolved serum free light chain (FLC) ratio \>=100; \>1 focal lesion on magnetic resonance imaging (MRI) studies.

   Measurable disease: Immunoglobulin (Ig) G myeloma (serum monoclonal paraprotein \[M-protein\] level \>= 0.5 gram/deciliter \[g/dL\] or urine M-protein level \>= 200 milligram\[mg\]/24 hours\[hrs\]); OR IgA, IgM, IgD, or IgE multiple myeloma (serum M-protein level \>= 0.2 g/dL or urine M-protein level \>= 200 mg/24 hrs); OR Light chain multiple myeloma (serum immunoglobulin free light chain \>= 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio)
3. Expected survival more than 3 months
4. No active infectious disease
5. Be able to understand the characteristics of the disease, voluntarily join this study protocol for treatment and follow-up
6. Have signed informed consent. Informed consent was obtained from the patients themselves or their immediate family members.

Exclusion Criteria:

1. Patients with active hepatitis B (HBV), hepatitis C (HCV), and other acquired, congenital immunodeficiency diseases.
2. Peripheral neuropathy or neuropathic pain(except extramedullary disease compression) Grade 2 or higher, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.
3. Plasma cell leukemia, non-bone-related extramedullary lesions
4. Severe thrombotic events before treatment
5. The presence of grade 2 or higher peripheral neuropathy before treatment
6. Liver dysfunction (alanine aminotransferase and aspartate aminotransferase ≥ 2.5 times the upper limit of normal value)
7. Total bilirubin ≥ 1.5 times the upper limit of normal value
8. Major surgery within 30 days before enrollment
9. Epilepsy, dementia and other mental abnormalities requiring drug treatment and cannot understand or follow the study protocol
10. According to the protocol or the investigator's judgment, the patient has a serious physical or mental illness that may interfere with the participation in this clinical study
11. Drug abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or the evaluation of the study results
12. Patients who are receiving other experimental drug treatment
13. Lactating or pregnant women
14. The investigator believes that the participant is not suitable for enrollment

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From enrollment to either disease progression or death whichever occurs first (approximately 5 years, or 8 years if the adaptive approach is decided at the interim)
measure: MRD Negative Rate
timeFrame: First time reached VGPR, then12,18,24 Months and every 6 months
Secondary outcomes:
measure: Very Good Partial Response (VGPR) or Better Rate
timeFrame: Approximately 5 years
measure: Overall Response Rate
timeFrame: Up to the end of the study (approximately 5 years)
measure: Duration of Response(DOR)
timeFrame: From initial documentation of response to the date of PD until approximately 5 years
measure: Overall Survival (OS)
timeFrame: From enrollment until the participant's death from any cause (up to approximately 5 years, or 8 years if the adaptive approach is decided at the interim)
measure: Complete Response (CR) or Better Rate
timeFrame: Approximately 5 years
Other outcomes:
Locations:
city: Changzhou
country: China
facility: Changzhou Second People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: The First Affiliated Hospital of Nanjing Medical University
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing First People's Hospital
state: Jiangsu
city: Nantong
country: China
facility: Affiliated Hospital of Nantong University
state: Jiangsu
city: Taizhou
country: China
facility: Taizhou People's Hospital
state: Jiangsu
city: Yancheng
country: China
facility: Yancheng First People's Hospital
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Lijuan Chen
role: STUDY_CHAIR
References: