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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06140966
• Other study ID #: D-KRD20230808
• Status: Recruiting
• Phase: Phase 2
• Start date: October 20, 2023
• Est. completion date: October 20, 2027

Study information

• Verified date: December 2023
• Source: Wuhan Union Hospital, China
• Contact: Chunyan Sun, MD
• Phone: +8602785726387
• Email: suncy0618[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: October 20, 2027
• Est. primary completion date: October 20, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia, Plasma Cell
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Primary Plasma Cell Leukemia

Intervention

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.
• 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.
• Lenalidomide
Given by mouth: days 1-7 of each Induction cycle; days 1-14 of each Consolidation cycle.
• 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
• Cisplatin
Given by vein: days 1-4 of each Induction cycle
• epirubicin
Given by vein: days 1-4 of each Induction cycle
• Cyclophosphamide
Given by vein: days 1-4 of each Induction cycle
• Etoposide
Given by vein: days 1-4 of each Induction cycle
• Melphalan
Given by vein: day -1 of Transplant

Procedure:
• ASCT
day 0 of Transplant

Drug:
• bortezomib
given by subcutaneous injection: days 1, 4, 8, and 11 of pretrial induction chemotherapy

Locations

Country	Name	City	State
China	Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Wuhan Union Hospital, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	2-year progression-free survival	2-year Progression-free survival of participants as determined by investigator assessment.	24 months
Secondary	progression-free survival	progression-free survival of participants as determined by investigator assessment.	36 months
Secondary	overall survival	overall survival of participants as determined by investigator assessment.	36 months
Secondary	overall response rate	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
Secondary	minimal residual disease negativity rate	Minimal Residual Disease (MRD) negativity rate as assessed by next generation sequencing.	36 months
Secondary	complete response rate	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
Secondary	duration of minimal residual disease negativity	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
Secondary	duration of response	determined by investigator assessment.	36 months
Secondary	adverse events	graded according to the Common Terminology Criteria for Adverse Events v5	collected until 3 months after treatment completion