Daratumumab in Combination With Bortezomib and Dexamethasone in Newly Diagnosed Transplant Ineligible Multiple Myeloma

NCT03695744 | Unknown Phase 2 DMC

• 1 other identifier: AMN006
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

Newly diagnosed Multiple Myeloma patients who are ineligible for a transplant have inferior outcomes to that of the transplant population. This is an area of high unmet need and calls for newer therapies with novel mechanisms of action to improve survival in this non-transplant eligible (NTE) group. Daratumumab is a monoclonal antibody that targets CD38 expressed at high levels on myeloma plasma cells. In phase 1/2 studies, it has demonstrated impressive single agent activity in relapse and refractory myeloma with a very acceptable toxicity profile. This set the stage for combinations with daratumumab to increase efficacy and improve outcomes of patients in both the relapse refractory and newly diagnosed settings. Two large Phase 2 trails using lenalidomide and dexamethasone or bortezomib and dexamethasone along with Daratumumab demonstarted the impressive efficacy of antibody based 3 drug combinations in the relapsed refractory myeloma setting. More recently a large clinical trial using a Bortezomib based 4 drug combination with Daratumumab was reported from Europe in the first-line treatment of transplant ineligible Myeloma patients showing very good survival outcomes. Hence the investigators hypothesize that the combination of Daratumumab with bortezomib and dexamethasone in the NTE population may therefore improve efficacy and clinical outcomes.

Conditions

Multiple Myeloma; Myeloma

Keywords

Myeloma; Daratumumab; Non-Transplant Eligible

Outcome Measures

Primary Outcomes (1)

• Overall Response

  Number of patients achieving responses as defined by the IMWG Criteria

  From the date of treatment commencement till the date of best response as per IMWG definitions, upto 3 years

Secondary Outcomes (2)

• PFS

  From date of commencement of trial treatment until the date of first documented progression or date of death from any cause, whichever occurs first assessed upto 100 months

• OS

  From commencement of trial treatment to death from any cause assessed upto 100 months

Study Arms (1)

Daratumumab Bortezomib Dexamethasone

EXPERIMENTAL

IV daratumumab 16mg/kg body weight weekly for weeks 1-9 followed by daratumumab 16mg/kg body weight once every 3 weeks from weeks 10 to 24 and then daratumumab 16mg/kg once every 4 weeks from weeks 25 onwards until disease progression; S.C bortezomib and PO Dexamethasone 40mg (starting dose of dexamethasone is 20mg once weekly for patients \>75 years old) once weekly for 9 months from start of study. After 9 months, patient only continues on daratumumab until progression.

Drug: Daratumumab; Drug: Bortezomib; Drug: Dexamethasone

Interventions

Daratumumab DRUG

Daratumumab

Daratumumab Bortezomib Dexamethasone

Bortezomib DRUG

Bortezomib

Daratumumab Bortezomib Dexamethasone

Dexamethasone DRUG

Dexamethasone

Daratumumab Bortezomib Dexamethasone

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed Multiple myeloma, diagnosed according to standard criteria, and in subjects who are not eligible for high dose Melphalan and stem cell transplant.
• Patients must have evaluable multiple myeloma with at least one of the following (within 21 days of starting treatment)
• Serum M-protein ≥ 0.5g/dL, or
• In subjects without detectable serum M-protein, Urine M-protein ≥ 200mg/24 hour, or serum free light chai (sFLC) \> 100mg/L (involved light chain) and an abnormal kappa/Lambda ratio
• Must have received no prior treatment. Short duration of steroids are acceptable.
• Males and females ≥ 18 years of age or \> country's legal age for adult consent
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
• Patients must meet the following clinical laboratory criteria with 21 days of starting treatment:
• Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet ≥ 50,000/mm3 (≥ 30,000/mm3 if myeloma involvement in the bone marrow is \>50%)
• Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.
• Calculated creatinine clearance ≥ 30mL/min.
• Written informed consent in accordance with federal, local and institutional guidelines

You may not qualify if:

• Female patients who are lactating or pregnant
• Multiple Myeloma of IgM subtype
• Glucocorticoid therapy (prednisolone \> 30mg/day or equivalent) within 7 days prior to informed consent obtained
• POEMS syndrome
• Plasma cell leukemia or circulating plasma cells ≥ 2 x 109/L
• Waldenstrom's Macroglobulinaemia
• Existing peripheral neuropathy of grade 2 or higher or presence of neuropathic pain
• Patients with known amyloidosis
• Any Chemotherapy with approved or investigational anticancer therapeutics within 21 days prior to starting Dara-VD treatment
• Focal radiation therapy within 7 days prior to start of Dara-VD. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to start of Dara-VD.
• Immunotherapy (excluding steroids) 21 days prior to start of Dara-VD
• Major surgery (excluding kyphoplasty) within 28 days prior to start of Dara-VD
• Active congestive heart failure (New York Heart Association \[NYHA\] Class III or IV), symptomatic ischaemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 4 months prior to informed consent obtained
• Known HIV seropositive, hepatitis C infection, and/or hepatitis B (except for patients with hepatitis B surface antigen or core antibody receiving and responding to antiviral therapy directed at hepatitis B: these patients are allowed)
• Patients with known cirrhosis

Sponsors & Collaborators

• Singapore General Hospital: lead
• International Myeloma Foundation: collaborator
• Janssen, LP: collaborator

Study Sites (2)

National University Hospital

Singapore, Singapore

Location

Singapore General Hospital

Singapore, Singapore

Location

Related Publications (1)

• Tan MSY, Nagarajan C, Ooi M, De Mel S, Binte Hashim NS, Li X, Chua A, Pokharkar Y, Tso A, Awasthi N, Durie B, Chen Y, Chng WJ. Daratumumab bortezomib and dexamethasone in transplant ineligible newly diagnosed elderly myeloma patients (AMN006)-a trial by Asian Myeloma Network (NCT03695744). Leuk Lymphoma. 2025 Dec 16:1-8. doi: 10.1080/10428194.2025.2602050. Online ahead of print.

  PMID: 41400977 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

daratumumab; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

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)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2018
• First Posted: October 4, 2018
• Study Start: October 2, 2019
• Primary Completion: September 30, 2021
• Study Completion: April 1, 2024
• Last Updated: July 10, 2023

Record last verified: 2023-07

Locations

SG (2)