None listed
Conditions
Brief summary
The primary purpose of this trial is to assess whether the addition of datatumumab to a velcade, cyclophosphamide and dexamethasone treatment regime will cause an improvement in disease progression free survival. Who is it for? You may be eligible to participate in this trial if you are aged 18 years or over, have been newly diagnosed with multiple myeloma and are not a candidate for high dose chemotherapy and autologous stem cell transplant. Study details Eligible participants will be assigned to either a velcade, cyclophosphamide and dexamethasone (VCD) or velcade, cyclophosphamide, dexamethasone and daratumumab (VCDD) treatment arm. Both arms will receive 9 35 day cycles of treatment with the VCDD arm continuing on daratumumab maintenance monthly until disease progression, unacceptable toxicity, or withdrawal of consent. Paricipants will be required to have blood samples taken at the beginning of each cycle along with a medical exam in order for researchers to monitor whether the treatment is safe and whether it is effectively treating the myeloma. It is hoped that the findings of this trial will establish the benefits of daratumumab in combination with VCD for the treatment of multiple myeloma patients early in the course of their disease.
Interventions
Daratumumab at a dose of 16 milligrams per kilogram intravenously day 1,8,15,22 of each 35 day cycle for cycles 1 & 2, then day 1 and 15 for cycles 3-6, thereafter day 1 for cycles 7-9, (Daratumumab cycles concurrent with Bortezomib, Cyclophosphamide and Dexamethasone treatment for 9 cycles).
Bortezomib 1.3 milligrams per metre squared subcutaneously days 1,8,15,22 of each 35 day cycle.
Cyclophosphamide 300 milligrams per metre squared by mouth day 1 of each 35 day cycle.
Dexamethasone 20mg by
Daratumumab at a dose of 16 milligrams per kilogram intravenously day 1,8,15,22 of each 35 day cycle for cycles 1 & 2, then day 1 and 15 for cycles 3-6, thereafter day 1 for cycles 7-9, (Daratumumab cycles concurrent with Bortezomib, Cyclophosphamide and Dexamethasone treatment for 9 cycles). Bortezomib 1.3 milligrams per metre squared subcutaneously days 1,8,15,22 of each 35 day cycle. Cyclophosphamide 300 milligrams per metre squared by mouth day 1 of each 35 day cycle. Dexamethasone 20mg by mouth day 1,8,15,22 of each 35 day cycle. Following 9 cycles of treatment subjects will receive maintenance treatment of Daratumumab 16mg per kg intravenously once every 4 weeks until disease progression, unacceptable toxicity, or withdrawal of consent.. Adherence monitored through hospital drug administration records and tablet adherence through drug packet return.
Sponsors
Alfred Health
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients 18 years or older. 2. Patients must have a diagnosis of symptomatic multiple myeloma as per IMWG criteria 3. Measureable disease 4. Newly diagnosed and not considered candidate for high-dose chemotherapy with autologous stem cell transplantation 5. Patients must be untreated apart from a brief course of corticosteroids or radiotherapy 6. No contraindication to the use of any of the study drugs 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 8. Patients must meet the following clinical laboratory criteria: a. ANC greater than or equal to 1.0 times 10 to the power of 9 per litre (G-CSF use is permitted) b. Platelet count greater than or equal to 70 times 10 to the power of 9 per litre for subjects in whom less than 50 percent of bone marrow nucleated cells are plasma cells; otherwise platelet count greater than 50 times 10 to the power of 9 per litre c. Total bilirubin less than or equal to 2 times upper limit of normal (ULN), except in subjects with Gilbert syndrome, then direct bilirubin less than or equal to 2 times ULN d. ALT and AST less than or equal to 5 times ULN 9. Voluntary written consent 10. Female patients who are postmenopausal or agree to use effective contraception 11. Male patients who agree to use effective contraception 12. Study site must be able to get correlative samples to the Alfred Hospital, Melbourne, Australia, within 24 hours of collection
Exclusion criteria
1. Patients with Amyloid light-chain (AL) amyloidosis, monoclonal gammopathy of uncertain significance or smouldering MM. 2. Female patients who are lactating or have a positive serum pregnancy test during the screening period. 3. Patient has greater than or equal to Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period. 4. Subject has significant airways disease according to the following definitions: a. Subject has known chronic obstructive pulmonary disease (COPD) with an Forced Expiratory Volume in 1 second (FEV1) less than 50 percent of predicted normal. b. Subject has had known moderate or severe persistent asthma within the last 2 years, or currently has uncontrolled asthma of any classification. (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study). 5. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, New York Heart Association (NYHA) class 3 or 4 heart failure symptoms, unstable angina, or myocardial infarction within the past 6 months. 6. Known ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive 7. Active malignancy with the exception of any of the following: a. Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer b. Adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for 2 years c. Stage I prostate cancer that does not require treatment d. Any other cancer from which the subject has been disease-free for greater than or equal to 2 years 8. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol. 9. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. 10. Participation in other clinical trials for the treatment of multiple myeloma, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.
Outcome results
None listed