Evaluating a new treatment for ultra high-risk multiple myeloma patients

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 is testing a new treatment plan for patients with ultra high-risk multiple myeloma to see if it can help them live longer and respond better to therapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (Academic / other)
• Drugs / interventions: daratumumab, chemotherapy, radiation, cyclophosphamide
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT06140966 on ClinicalTrials.gov

What this trial studies

This study investigates the effectiveness and safety of a treatment regimen combining daratumumab and carfilzomib-based induction, consolidation, and maintenance therapy in patients with ultra high-risk, newly diagnosed multiple myeloma. Participants will undergo 2-4 cycles of induction therapy followed by autologous stem cell transplantation (ASCT), consolidation therapy, and then maintenance therapy. The goal is to improve survival outcomes for patients who are typically less responsive to existing treatments. The study focuses on patients with specific high-risk characteristics, including 'double-hit' multiple myeloma and primary plasma cell leukemia.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with newly diagnosed ultra high-risk multiple myeloma who are eligible for intensive chemotherapy and ASCT.

Not a fit: Patients with low-risk multiple myeloma or those who have previously received systemic therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates for patients with ultra high-risk multiple myeloma.

How similar studies have performed: While there have been studies on multiple myeloma treatments, this specific combination approach in ultra high-risk patients is relatively novel.

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.

Where this trial is running

Wuhan, Hubei

• Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)

Study contacts

• Study coordinator: Chunyan Sun, MD

Conditions Multiple Myeloma; Primary Plasma Cell Leukemia; Extramedullary Multiple Myeloma; Daratumumab; Carfilzomib; Ultra High-risk; Autologous stem cell transplant; Double hit