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

  • STATUS
    Recruiting
  • End date
    Apr 24, 2024
  • participants needed
    63
  • sponsor
    Singapore General Hospital
Updated on 24 January 2021
monoclonal antibodies
melphalan
bone marrow procedure
dexamethasone
lenalidomide
neutrophil count
bortezomib
monoclonal protein
daratumumab

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.

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.

Details
Condition Multiple Myeloma, Lymphoproliferative Disorder, Lymphoproliferative disorders, multiple myeloma (mm)
Treatment Dexamethasone, Bortezomib, Daratumumab
Clinical Study IdentifierNCT03695744
SponsorSingapore General Hospital
Last Modified on24 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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

Exclusion Criteria

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
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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note