Multiple MyelomaPhase 2NCT03695744
Daratumumab in Combination With Bortezomib and Dexamethasone in Newly Diagnosed Transplant Ineligible Multiple Myeloma
A Phase 2 study testing Daratumumab, Bortezomib and Dexamethasone in people with Multiple Myeloma and Myeloma, run by Singapore General Hospital at 2 sites in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Multiple Myeloma, Myeloma
- What is being tested?
- Daratumumab, Bortezomib and Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 2 sitesSingapore
- Study dates
- 2 Oct 2019to Apr 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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
Who cannot join
- 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
Show all 28Show fewer
- 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
- Patients with creatinine clearance <30m/min
- Second malignancy within the past 3 years except:
- Adequately treated basal cell or squamous cell skin cancer
- Carcinoma in situ of the cervix
- Breast carcinoma in situ with full surgical resection
- Patients with myelodysplastic syndrome
- Patients with steroid/bortezomib hypersensitivity
- Patients previously treated with daratumumab or other anti-CD38 antibodies.
- Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to starting Dara-VD treatment
- Contraindication to any of the required concomitant drugs or supportive treatments
- Any clinically significant medical disease or psychiatric condition that, in the investigator's opinion, may interfere with protocol adherence or a patient's ability to give informed consent.
- Known COPD with FEV1 < 50% of normal.
- Moderate or severe persistent asthma within the last 2 years, or uncontrolled asthma of any classification
Trial locations and contacts
2 sites in 1 country.
Singapore2 sites
National University Hospital
Singapore
Singapore General Hospital
Singapore
About this study
Official title: AMN006 - Phase 2 Study of Daratumumab in Combination With Bortezomib and Dexamethasone in Newly Diagnosed Transplant Ineligible Multiple Myeloma Patients
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.
Read the detailed description
Newly diagnosed Multiple Myeloma patients who ineligible for a transplant have inferior outcomes compared 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 better improve survival in this non-transplant eligible (NTE) group. Currently NTE patients will be treated with a Bortezomib based or Lenalidomide based doublet or triplet regimen as first-line.
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 and is a promising new treatment. 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. Addition of daratumumab to any number of the backbone regimes have been shown to be of good efficacy. 2 phase 1 / 2 studies established the dosing regimen for Daratumumab as a single agent in patients who relapse after prior lenalidomide and bortezomib.
More recently, results from 2 randomised studies comparing Daratumumab plus lenalidomide and dexamethasone compared to lenalidomide and dexamethasone, and Daratumumab plus bortezomib and dexamethasone compared to bortezomib and dexamethasone, showed that the addition of Daratumumab significantly improved response and progression free survival, including a high minimal residual disease (MRD) negative rate of more than 20% in the relapse myeloma populations.
Another recent study showed that a different 4 drug combination of Daratumumab, bortezomib and Melphalan and Prednisolone in the front line setting of non-transplant Myeloma had promising response rates and was a quite tolerable combination.
All the above Daratumumab trials demostrated that deeper responses are achieved by antibody - Proteasome inhibitor or Antibody - ImiD combinations. It is known that deeper response in myeloma are associated with longer progression free and overall survival. Hence this trial using the three drug combination of Daratumumab, Bortezomib and Dexamethasone is proposed to explore its efficacy by demonstarting an improvement in overall response rates, complete response rates and to document its safety/tolerability in our population.
- Conditions
- Multiple Myeloma, Myeloma
- Being tested
- Daratumumab, Bortezomib, Dexamethasone
- Keywords
- Myeloma, Daratumumab, Non-Transplant Eligible
- Medical subject headings
- Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaratumumabDrug
Daratumumab
BortezomibDrug
Bortezomib
DexamethasoneDrug
Dexamethasone
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Daratumumab; Drug: Bortezomib; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response
Number of patients achieving responses as defined by the IMWG Criteria
Measured: From the date of treatment commencement till the date of best response as per IMWG definitions, upto 3 years
Secondary outcomes (2)
PFS
Progression Free Survival
Measured: 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
Overall Survival
Measured: From commencement of trial treatment to death from any cause assessed upto 100 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2018
- Study start2 Oct 2019
- Primary completion30 Sep 2021
- Study completionApr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Singapore General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Singapore General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- International Myeloma Foundation, Janssen, LP
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03695744
- Sponsor's protocol ID
- AMN006
- Status last verified
- Jul 2023
- First submitted
- 11 Sep 2018
- Last updated
- 10 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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. 2026 Feb;67(3):600-607. doi: 10.1080/10428194.2025.2602050. Epub 2025 Dec 16.
PubMed 41400977
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AMN006 - Phase 2 Study of Daratumumab in Combination With Bortezomib and Dexamethasone in Newly Diagnosed Transplant Ineligible Multiple Myeloma Patients
- ClinicalTrials.gov ID
- NCT03695744
- Acronym / sponsor ID
- AMN006
- Conditions
- Multiple Myeloma, Myeloma
- Keywords
- Myeloma, Daratumumab, Non-Transplant Eligible
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Singapore General HospitalUniversity, hospital or other
- Collaborators
- International Myeloma Foundation, Janssen, LP
- Study start
- 2 Oct 2019 (actual)
- Primary completion
- 30 Sep 2021 (actual)
- Study completion
- Apr 2024 (estimated)
- First posted
- 4 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Newly diagnosed Multiple Myeloma patients who ineligible for a transplant have inferior outcomes compared 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 better improve survival in this non-transplant eligible (NTE) group. Currently NTE patients will be treated with a Bortezomib based or Lenalidomide based doublet or triplet regimen as first-line.
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 and is a promising new treatment. 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. Addition of daratumumab to any number of the backbone regimes have been shown to be of good efficacy. 2 phase 1 / 2 studies established the dosing regimen for Daratumumab as a single agent in patients who relapse after prior lenalidomide and bortezomib.
More recently, results from 2 randomised studies comparing Daratumumab plus lenalidomide and dexamethasone compared to lenalidomide and dexamethasone, and Daratumumab plus bortezomib and dexamethasone compared to bortezomib and dexamethasone, showed that the addition of Daratumumab significantly improved response and progression free survival, including a high minimal residual disease (MRD) negative rate of more than 20% in the relapse myeloma populations.
Another recent study showed that a different 4 drug combination of Daratumumab, bortezomib and Melphalan and Prednisolone in the front line setting of non-transplant Myeloma had promising response rates and was a quite tolerable combination.
All the above Daratumumab trials demostrated that deeper responses are achieved by antibody - Proteasome inhibitor or Antibody - ImiD combinations. It is known that deeper response in myeloma are associated with longer progression free and overall survival. Hence this trial using the three drug combination of Daratumumab, Bortezomib and Dexamethasone is proposed to explore its efficacy by demonstarting an improvement in overall response rates, complete response rates and to document its safety/tolerability in our population.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Daratumumab Bortezomib Dexamethasone | Experimental | Drug: Daratumumab, Drug: Bortezomib, Drug: DexamethasoneIV 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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)
- 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
Key exclusion criteria (28 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DaratumumabDaratumumab | Drug | Daratumumab Bortezomib Dexamethasone |
| BortezomibBortezomib | Drug | Daratumumab Bortezomib Dexamethasone |
| DexamethasoneDexamethasone | Drug | Daratumumab Bortezomib Dexamethasone |
Primary outcome
Overall Response
Time frame: From the date of treatment commencement till the date of best response as per IMWG definitions, upto 3 years
Number of patients achieving responses as defined by the IMWG Criteria
2 secondary outcomes
PFS
Time frame: 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
Time frame: From commencement of trial treatment to death from any cause assessed upto 100 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2023.
- Derived from this study: PubMed 41400977Tan 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. 2026 Feb;67(3):600-607. doi: 10.1080/10428194.2025.2602050. Epub 2025 Dec 16.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Daratumumab, Bortezomib and Dexamethasone in people with Multiple Myeloma and Myeloma, run by Singapore General Hospital at 2 sites in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response (time frame: From the date of treatment commencement till the date of best response as per IMWG definitions, upto 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03695744, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2023.