Trial Title:
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
NCT ID:
NCT06140966
Condition:
Multiple Myeloma
Primary Plasma Cell Leukemia
Extramedullary Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Leukemia, Plasma Cell
Dexamethasone
Cyclophosphamide
Melphalan
Etoposide
Lenalidomide
Bortezomib
Epirubicin
Daratumumab
Conditions: Keywords:
Daratumumab
Carfilzomib
Multiple Myeloma
Ultra High-risk
Primary Plasma Cell Leukemia
Extramedullary Multiple Myeloma
Autologous stem cell transplant
Double hit
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Daratumumab
Description:
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.
Arm group label:
Study Treatment
Other name:
Darzalex
Intervention type:
Drug
Intervention name:
Carfilzomib
Description:
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.
Arm group label:
Study Treatment
Other name:
Kyprolis
Intervention type:
Drug
Intervention name:
Lenalidomide
Description:
Given by mouth: days 1-7 of each Induction cycle; days 1-14 of each Consolidation cycle.
Arm group label:
Study Treatment
Other name:
Revlimid
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
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
Arm group label:
Study Treatment
Other name:
Baycadron
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Given by vein: days 1-4 of each Induction cycle
Arm group label:
Study Treatment
Other name:
Platinol
Intervention type:
Drug
Intervention name:
epirubicin
Description:
Given by vein: days 1-4 of each Induction cycle
Arm group label:
Study Treatment
Other name:
Pharmorubicin
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Given by vein: days 1-4 of each Induction cycle
Arm group label:
Study Treatment
Other name:
Cytoxan
Intervention type:
Drug
Intervention name:
Etoposide
Description:
Given by vein: days 1-4 of each Induction cycle
Arm group label:
Study Treatment
Other name:
Eposin
Intervention type:
Drug
Intervention name:
Melphalan
Description:
Given by vein: day -1 of Transplant
Arm group label:
Study Treatment
Other name:
Alkeran
Intervention type:
Procedure
Intervention name:
ASCT
Description:
day 0 of Transplant
Arm group label:
Study Treatment
Other name:
autologous stem cell transplantation
Intervention type:
Drug
Intervention name:
bortezomib
Description:
given by subcutaneous injection: days 1, 4, 8, and 11 of pretrial induction chemotherapy
Arm group label:
Study Treatment
Other name:
Velcade
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 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.
Criteria for eligibility:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Address:
City:
Wuhan
Country:
China
Status:
Recruiting
Contact:
Last name:
Chunyan Sun, MD
Phone:
+8602785726387
Email:
suncy0618@163.com
Contact backup:
Last name:
Jian Xu, MD
Phone:
+8602785726006
Email:
xujian01222@163.com
Investigator:
Last name:
Chunyan Sun, MD
Email:
Principal Investigator
Investigator:
Last name:
Jian Xu, MD
Email:
Sub-Investigator
Start date:
October 20, 2023
Completion date:
October 20, 2027
Lead sponsor:
Agency:
Wuhan Union Hospital, China
Agency class:
Other
Source:
Wuhan Union Hospital, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06140966
