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

NCT06140966 | Recruiting Phase 2

• 1 other identifier: D-KRD20230808
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Multiple Myeloma; Primary Plasma Cell Leukemia; Extramedullary Multiple Myeloma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 2-year progression-free survival

  2-year Progression-free survival of participants as determined by investigator assessment.

  24 months

Secondary Outcomes (8)

• progression-free survival

  36 months

• overall survival

  36 months

• overall response rate

  36 months

• minimal residual disease negativity rate

  36 months

• complete response rate

  36 months

Study Arms (1)

Study Treatment

EXPERIMENTAL

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; Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Cisplatin; Drug: epirubicin; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Melphalan; Procedure: ASCT; Drug: bortezomib

Interventions

Daratumumab DRUG

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.

Also known as: Darzalex

Study Treatment

Carfilzomib DRUG

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.

Also known as: Kyprolis

Study Treatment

Lenalidomide DRUG

Given by mouth: days 1-7 of each Induction cycle; days 1-14 of each Consolidation cycle.

Also known as: Revlimid

Study Treatment

Dexamethasone DRUG

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

Also known as: Baycadron

Study Treatment

Cisplatin DRUG

Given by vein: days 1-4 of each Induction cycle

Also known as: Platinol

Study Treatment

epirubicin DRUG

Given by vein: days 1-4 of each Induction cycle

Also known as: Pharmorubicin

Study Treatment

Cyclophosphamide DRUG

Given by vein: days 1-4 of each Induction cycle

Also known as: Cytoxan

Study Treatment

Etoposide DRUG

Given by vein: days 1-4 of each Induction cycle

Also known as: Eposin

Study Treatment

Melphalan DRUG

Given by vein: day -1 of Transplant

Also known as: Alkeran

Study Treatment

ASCT PROCEDURE

day 0 of Transplant

Also known as: autologous stem cell transplantation

Study Treatment

bortezomib DRUG

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

Also known as: Velcade

Study Treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients must be either untreated or have not received systemic MM therapy. Prior bisphosphonates and localized radiation are allowed.
• Aged 18 years to 70 years.
• Fit for intensive chemotherapy and autologous stem cell transplant (at clinician's discretion).
• Eastern Cooperative Oncology Group (ECOG) score ≤2 before induction chemotherapy.

You may not qualify if:

• No evidence of high-risk disease.
• Primary diagnosis of Waldenstrom's disease/POEMS syndrome/light chain amyloidosis.
• Received therapy for multiple myeloma.
• Prior or concurrent invasive malignancies.
• Eastern Cooperative Oncology Group (ECOG) score \>2 before induction chemotherapy.
• Clinically significant allergies or intolerance to daratumumab,carfilzomib,lenalidomide, dexamethasone, cisPlatin, epirubicin, cyclophosphamide,melphalan, and etoposide.
• Participants with contraindication to thromboprophylaxis.
• Any uncontrolled or severe cardiovascular or pulmonary disease.
• Platelet count \< 50,000/μL, absolute neutrophil count \<1000/μL, and haemoglobin \<60 g/L before induction chemotherapy.
• 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).
• Known to be seropositive for history of HIV or known to have active hepatitis B or hepatitis C.
• 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.
• 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.
• Known/underlying medical conditions that, in the investigator's opinion, would make the administration of the study drug hazardous.
• 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.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead

Study Sites (1)

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; carfilzomib; Lenalidomide; Dexamethasone; Calcium Dobesilate; Cisplatin; Epirubicin; Cyclophosphamide; Etoposide; Melphalan; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines

Central Study Contacts

Chunyan Sun, MD

CONTACT

+8602785726387; suncy0618@163.com

Jian Xu, MD

CONTACT

+8602785726006; xujian01222@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 14, 2023
• First Posted: November 21, 2023
• Study Start: October 20, 2023
• Primary Completion (Estimated): October 20, 2026
• Study Completion (Estimated): October 20, 2027
• Last Updated: April 16, 2025

Record last verified: 2025-04

Locations

CN (1)