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

This is an interventional treatment trial for Multiple Myeloma focused on measuring Myeloma, Daratumumab, Non-Transplant Eligible Read More

Inclusion Criteria:

1. Newly diagnosed Multiple myeloma, diagnosed according to standard criteria, and in subjects who are not eligible for high dose Melphalan and stem cell transplant.

2. Patients must have evaluable multiple myeloma with at least one of the following (within 21 days of starting treatment)

   1. Serum M-protein ≥ 0.5g/dL, or
   2. 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
3. Must have received no prior treatment. Short duration of steroids are acceptable.
4. Males and females ≥ 18 years of age or > country's legal age for adult consent
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2

6. Patients must meet the following clinical laboratory criteria with 21 days of starting treatment:

   1. Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet ≥ 50,000/mm3 (≥ 30,000/mm3 if myeloma involvement in the bone marrow is >50%)
   2. Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.
   3. Calculated creatinine clearance ≥ 30mL/min.
7. Written informed consent in accordance with federal, local and institutional guidelines

Exclusion Criteria:

1. Female patients who are lactating or pregnant
2. Multiple Myeloma of IgM subtype
3. Glucocorticoid therapy (prednisolone > 30mg/day or equivalent) within 7 days prior to informed consent obtained
4. POEMS syndrome
5. Plasma cell leukemia or circulating plasma cells ≥ 2 x 109/L
6. Waldenstrom's Macroglobulinaemia
7. Existing peripheral neuropathy of grade 2 or higher or presence of neuropathic pain
8. Patients with known amyloidosis
9. Any Chemotherapy with approved or investigational anticancer therapeutics within 21 days prior to starting Dara-VD treatment
10. 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.
11. Immunotherapy (excluding steroids) 21 days prior to start of Dara-VD
12. Major surgery (excluding kyphoplasty) within 28 days prior to start of Dara-VD
13. 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
14. 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)
15. Patients with known cirrhosis
16. Patients with creatinine clearance <30m/min

17. Second malignancy within the past 3 years except:

    1. Adequately treated basal cell or squamous cell skin cancer
    2. Carcinoma in situ of the cervix
    3. Breast carcinoma in situ with full surgical resection
18. Patients with myelodysplastic syndrome
19. Patients with steroid/bortezomib hypersensitivity
20. Patients previously treated with daratumumab or other anti-CD38 antibodies.
21. Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to starting Dara-VD treatment
22. Contraindication to any of the required concomitant drugs or supportive treatments
23. 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.
24. Known COPD with FEV1 < 50% of normal.
25. Moderate or severe persistent asthma within the last 2 years, or uncontrolled asthma of any classification