Overview
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
Status:
Recruiting
Recruiting
Trial end date:
2027-10-20
2027-10-20
Target enrollment:
0
0
Participant gender:
All
All
Summary
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 myelomaPhase:
Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Wuhan Union Hospital, ChinaTreatments:
Bortezomib
Cyclophosphamide
Daratumumab
Dexamethasone
Epirubicin
Etoposide
Lenalidomide
Melphalan
Criteria
Inclusion Criteria:1. 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.
2. Patients must be either untreated or have not received systemic MM therapy. Prior
bisphosphonates and localized radiation are allowed.
3. Aged 18 years to 70 years.
4. Fit for intensive chemotherapy and autologous stem cell transplant (at clinician's
discretion).
5. Eastern Cooperative Oncology Group (ECOG) score ≤2 before induction chemotherapy.
Exclusion Criteria:
1. No evidence of high-risk disease.
2. Primary diagnosis of Waldenstrom's disease/POEMS syndrome/light chain amyloidosis.
3. Received therapy for multiple myeloma.
4. Prior or concurrent invasive malignancies.
5. Eastern Cooperative Oncology Group (ECOG) score >2 before induction chemotherapy.
6. Clinically significant allergies or intolerance to
daratumumab,carfilzomib,lenalidomide, dexamethasone, cisPlatin, epirubicin,
cyclophosphamide,melphalan, and etoposide.
7. Participants with contraindication to thromboprophylaxis.
8. Any uncontrolled or severe cardiovascular or pulmonary disease.
9. Platelet count < 50,000/μL, absolute neutrophil count <1000/μL, and haemoglobin <60
g/L before induction chemotherapy.
10. 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).
11. Known to be seropositive for history of HIV or known to have active hepatitis B or
hepatitis C.
12. 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.
13. 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.
14. Known/underlying medical conditions that, in the investigator's opinion, would make
the administration of the study drug hazardous.
15. 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.
16. 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.
17. 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.
18. Known or suspected of not being able to comply with the study protocol.