Study to Evaluate the Safety and Efficacy of Daratumumab and Carfilzomib-based Induction/Consolidation/Maintenance Therapy in Transplant-eligible, Ultra High-risk, Newly Diagnosed Multiple Myeloma
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Daratumumab, Carfilzomib, Lenalidomide, Dexamethasone.
- Who it may be relevant to
- Registry conditions: Multiple Myeloma, Primary Plasma Cell Leukemia, Extramedullary Multiple Myeloma. Basic parameters: 18 years — 70 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- China
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Clinical Study to Evaluate the Safety and Efficacy of Daratumumab and Carfilzomib-based Induction/Consolidation/Maintenance Therapy in Transplant-eligible, Ultra High-risk, Newly Diagnosed Multiple Myeloma
Overview
This study will assess whether the combination of daratumumab and carfilzomib-based Induction/Consolidation/Maintenance Therapy with ASCT improves the outcome of patients with ultra high-risk, newly diagnosed multiple myeloma
Detailed description
Survival outcomes for patients with newly diagnosed multiple myeloma (MM) have improved substantially in the past decades, due to the introduction of novel therapeutic strategies. Unfortunately, patients with ultra-high-risk MM, including "double-hit" MM, extramedullary MM (EMM), and primary plasma cell leukemia (pPCL), have a significantly worse prognosis and benefit less from current therapeutic strategies. This study aims to investigate whether a treatment regimen combining daratumumab and carfilzomib-based Induction/Consolidation/Maintenance Therapy with autologous stem cell transplantation (ASCT) can improve the survival outcomes of newly diagnosed, transplant-eligible, ultra high-risk multiple myeloma patients. In the study, participants will receive induction therapy with 2-4 cycles of Dara-KRd-PACE, followed by ASCT, 4 cycles of Dara-KRd consolidation, and then maintenance with 12 cycles of Dara-Kd.
Interventions
- Drug Daratumumab
Given by vein: days 1 and 8 of each Induction cycle; days 1 and 15 of each Consolidation cycle; and day 1of each Maintenance cycle. - Drug Carfilzomib
Given by vein: days 1,2,8 and 9 of each Induction cycle; days 1, 2, 8, 9,15, and 16 of each Consolidation cycle; days 1, 2,15, and 16 of each Maintenance cycle. - Drug Lenalidomide
Given by mouth: days 1-7 of each Induction cycle; days 1-14 of each Consolidation cycle. - Drug Dexamethasone
Given by mouth or by vein: days 1, 8, 15, and 22 of each Induction cycle; days 1, 8, 15, and 22 of each Consolidation cycle; and days 1 and 15 of every cycle during Maintenance - Drug Cisplatin
Given by vein: days 1-4 of each Induction cycle - Drug epirubicin
Given by vein: days 1-4 of each Induction cycle - Drug Cyclophosphamide
Given by vein: days 1-4 of each Induction cycle - Drug Etoposide
Given by vein: days 1-4 of each Induction cycle - Drug Melphalan
Given by vein: day -1 of Transplant - Procedure ASCT
day 0 of Transplant
Primary outcome measures
- 2-year progression-free survival [Time frame: 24 months]
Secondary outcome measures (8)
- progression-free survival [Time frame: 36 months]
- overall survival [Time frame: 36 months]
- overall response rate [Time frame: 36 months]
- minimal residual disease negativity rate [Time frame: 36 months]
- complete response rate [Time frame: 36 months]
- duration of minimal residual disease negativity [Time frame: 36 months]
- duration of response [Time frame: 36 months]
- adverse events [Time frame: collected until 3 months after treatment completion]
Eligibility criteria
Inclusion criteria
- Patients must have newly diagnosed ultra high-risk disease, as defined by one of the following:1)"Double hit"Multiple Myeloma (≥2 adverse markers: t(4;14), t(14;16), t(14;20), 1q21+, del(17p),p53 mutation) ,2)Extramedullary Multiple Myeloma, 3) primary plasma cell leukemia.
- Patients must be either untreated or have not received systemic MM therapy. Prior bisphosphonates and localized radiation are allowed.
- Aged 18 years to 70 years.
- Fit for intensive chemotherapy and autologous stem cell transplant (at clinician's discretion).
- Eastern Cooperative Oncology Group (ECOG) score ≤2 before induction chemotherapy.
Exclusion criteria
- No evidence of high-risk disease.
- Primary diagnosis of Waldenstrom's disease/POEMS syndrome/light chain amyloidosis.
- Received therapy for multiple myeloma.
- Prior or concurrent invasive malignancies.
- Eastern Cooperative Oncology Group (ECOG) score >2 before induction chemotherapy.
- Clinically significant allergies or intolerance to daratumumab,carfilzomib,lenalidomide, dexamethasone, cisPlatin, epirubicin, cyclophosphamide,melphalan, and etoposide.
- Participants with contraindication to thromboprophylaxis.
- Any uncontrolled or severe cardiovascular or pulmonary disease.
- Platelet count < 50,000/μL, absolute neutrophil count <1000/μL, and haemoglobin <60 g/L before induction chemotherapy.
- Calculated creatinine clearance <30 mL/min, alanine transaminase (ALT) or aspertate aminotransferase (AST) >3 times upper limit of normal (ULN). Bilirubin >2 times ULN, except in participants with congenital bilirubinemia, such as Gilbert syndrome (direct bilirubin >2.0 times ULN).
- Known to be seropositive for history of HIV or known to have active hepatitis B or hepatitis C.
- Ejection fraction by echocardiogram (ECHO) ≥ 45%, pulmonary function studies <50% of predicted on mechanical aspects (Forced Expiratory Volume 1 (FEV1), Forced Vital Capacity (FVC) and diffusion capacity (DLCO) < 50% of predicted.
- Uncontrolled or severe cardiovascular or pulmonary disease, clinically significant cardiac disease, uncontrolled diabetes mellitus, or other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.
- Known/underlying medical conditions that, in the investigator's opinion, would make the administration of the study drug hazardous.
- Participant is a woman who is pregnant, or breast feeding, or planning to become pregnant while enrolled in this trial or within at least 6 months after the last dose of trial treatment. Or, participant is a man who plans to father a child while taking part in this trial or within at least 6 months after the last dose of trial treatment.
- Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks before treatment protocol registration or is currently enrolled in an interventional investigational study.
- Major surgery within 2 weeks before treatment protocol registration or has not fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study. Kyphoplasty or vertebroplasty is not considered major surgery.
- Known or suspected of not being able to comply with the study protocol.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
China · 1 center
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Sc — Wuhan
Identifiers
NCT: NCT06140966 · D-KRD20230808