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

April 12, 2025 updated by: Chunyan Sun, Wuhan Union Hospital, China

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

54

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Hubei
      • Wuhan, Hubei, China
        • Recruiting
        • Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
        • Principal Investigator:
          • Chunyan Sun, MD
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Jian Xu, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Study Treatment

Pretrial induction chemotherapy (if required): bortezomib, cyclophosphamid, dexamethasone (VCD).

Induction Chemotherapy: Daratumumab, Carfilzomib,Lenalidomide, Dexamethasone, CisPlatin, epirubicin, Cyclophosphamide and Etoposide (Dara-KRd-PACE).

Autologous Stem Cell Transplant (ASCT) : Melphalan, ASCT.

Consolidation: Daratumumab, Carfilzomib, Lenalidomide, Dexamethasone (Dara-KRd).

Maintenance: Daratumumab, Carfilzomib, and Dexamethasone (Dara-Kd).
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.
Other Names:
  • Darzalex
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.
Other Names:
  • Kyprolis
Drug: Lenalidomide
Given by mouth: days 1-7 of each Induction cycle; days 1-14 of each Consolidation cycle.
Other Names:
  • Revlimid
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
Other Names:
  • Baycadron
Drug: Cisplatin
Given by vein: days 1-4 of each Induction cycle
Other Names:
  • Platinol
Drug: epirubicin
Given by vein: days 1-4 of each Induction cycle
Other Names:
  • Pharmorubicin
Drug: Cyclophosphamide
Given by vein: days 1-4 of each Induction cycle
Other Names:
  • Cytoxan
Drug: Etoposide
Given by vein: days 1-4 of each Induction cycle
Other Names:
  • Eposin
Drug: Melphalan
Given by vein: day -1 of Transplant
Other Names:
  • Alkeran
Procedure: ASCT
day 0 of Transplant
Other Names:
  • autologous stem cell transplantation
Drug: bortezomib
given by subcutaneous injection: days 1, 4, 8, and 11 of pretrial induction chemotherapy
Other Names:
  • Velcade

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
2-year progression-free survival
Time Frame: 24 months
2-year Progression-free survival of participants as determined by investigator assessment.
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
progression-free survival
Time Frame: 36 months
progression-free survival of participants as determined by investigator assessment.
36 months
overall survival
Time Frame: 36 months
overall survival of participants as determined by investigator assessment.
36 months
overall response rate
Time Frame: 36 months
Overall response rate as determined by the 2016 International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma and 2013 IMWG Response Criteria for Plasma cell leukemia by Independent Review Committee (IRC) and investigator assessment.
36 months
minimal residual disease negativity rate
Time Frame: 36 months
Minimal Residual Disease (MRD) negativity rate as assessed by next generation sequencing.
36 months
complete response rate
Time Frame: 36 months
complete response rate as determined by the 2016 International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma and 2013 IMWG Response Criteria for Plasma cell leukemia by Independent Review Committee (IRC) and investigator assessment.
36 months
duration of minimal residual disease negativity
Time Frame: 36 months
determined by the 2016 International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma and 2013 IMWG Response Criteria for Plasma cell leukemia by Independent Review Committee (IRC) and investigator assessment.
36 months
duration of response
Time Frame: 36 months
determined by investigator assessment.
36 months
adverse events
Time Frame: collected until 3 months after treatment completion
graded according to the Common Terminology Criteria for Adverse Events v5
collected until 3 months after treatment completion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wuhan Union Hospital, China

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 20, 2023

Primary Completion (Estimated)

October 20, 2026

Study Completion (Estimated)

October 20, 2027

Study Registration Dates

First Submitted

November 14, 2023

First Submitted That Met QC Criteria

November 18, 2023

First Posted (Actual)

November 21, 2023

Study Record Updates

Last Update Posted (Actual)

April 16, 2025

Last Update Submitted That Met QC Criteria

April 12, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D-KRD20230808

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Multiple Myeloma

Clinical Trials on Daratumumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Uzbekistan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe