None listed
Conditions
Brief summary
This study will determine the effectiveness of a Carfilzomib (Kyprolis) based induction with autologous bone marrow transplant and Carfilzomib (Kyprolis) post-transplant consolidation in patients with untreated Myeloma. Who is it for? You may be eligible to join this study if you are aged 18 years or above, have been newly diagnosed with symptomatic multiple myeloma and are eligible for bone marrow transplant. Study details: All participants in this study will receive 5 cycles of Carfilzomib (Kyprolis) 56mg/m2 by intravenous infusion (i.e. directly into the vein) on Days 1, 2, 8, 9, 15,16 (except 20mg/m2 on Day 1 and 2 of the first cycle) Cyclophosphamide 300mg/m2 orally on Days 1, 8, 15 and Dexamethasone 20mg orally on Days 1, 2, 8, 9, 15, 16 for five 28 day cycles. This will be followed by a stem cell collection and autologous bone marrow transplant according to local institutional guidelines. Post-transplant consolidation therapy will consist of 4 cycles of Carfilzomib (Kyprolis) 56mg/m2 by intravenous infusion (i.e. directly into the vein) on days 1, 2, 8, 9, 15,16 Thalidomide 100mg daily orally (continuously), Dexamethasone 20mg orally on Days 1, 2, 8, 9, 15 ,16 for four 28 day cycles starting 3 months post-transplant. The study will monitor the disease response, adverse events, progression free survival and overall survival in each patient for up to 5 years. Carfilzomib (Kyprolis) is not registered for use by Medsafe in New Zealand but has been approved by the FDA. Cyclophosphamide and Dexamethasone are approved drugs currently being used to treat Myeloma.
Interventions
This is a Phase 2, multicenter, open-label; non-randomized study in transplant-eligible patients with newly diagnosed Multiple Myeloma. Participants will receive the following:
Induction: Carfilzomib (Kyprolis) 56mg/m2 by intravenous infusion on D1, 2, 8, 9, 15,16 (except 20mg/m2 on D1 and 2 of the first cycle) Cyclophosphamide 300mg/m2 orally on D1, 8, 15 and Dexamethasone 20mg orally on D1, 2, 8, 9, 15 ,16 for five 28 day cycles.
Transplant: Stem cell mobilization will start following
This is a Phase 2, multicenter, open-label; non-randomized study in transplant-eligible patients with newly diagnosed Multiple Myeloma. Participants will receive the following: Induction: Carfilzomib (Kyprolis) 56mg/m2 by intravenous infusion on D1, 2, 8, 9, 15,16 (except 20mg/m2 on D1 and 2 of the first cycle) Cyclophosphamide 300mg/m2 orally on D1, 8, 15 and Dexamethasone 20mg orally on D1, 2, 8, 9, 15 ,16 for five 28 day cycles. Transplant: Stem cell mobilization will start following completion of the 5th induction cycle and will be done according to local institutional guidelines. Autologous bone marrow transplant will be done following stem cell collection also according to local institutional guidelines. If patients become ineligible for transplant during the course of induction therapy or stem cell mobilization, Stem cell mobilization and/or autologous BMT can be omitted. Patients may then start consolidation therapy as below, if further treatment is not precluded. Consolidation: Carfilzomib (Kyprolis) 56mg/m2 by intravenous infusion on D1, 2, 8, 9, 15,16. Thalidomide 100mg daily taken orally(continuously) Dexamethasone 20mg taken orally D1, 2, 8, 9, 15 ,16 for four 28 day cycles starting 3 months post Autologous Bone Marrow Transplant (ABMT)
Sponsors
North Shore Haematology Clinical Trial Unit
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Disease-related: 1.Newly diagnosed symptomatic multiple myeloma 2.Transplant-eligible (according to local criteria) Demographic: 3.Age 18- 70years 4.Life expectancy greater than or equal to 3 months 5.Eastern Cooperative Oncology Group (ECOG) performance status 0–2 Laboratory 6.Adequate hepatic function, with serum ALT less than or equal to 3.5 times the upper limit of normal and serum direct bilirubin less than or equal to 34 micromol/L within 14 days prior to enrollment 7.Absolute neutrophil count (ANC) greater than or equal to 1.0 × 109/L within 14 days prior to enrollment 8.Hemoglobin greater than or equal to 80 g/L within 14 days prior to enrollment (subjects may be receiving red blood cell [RBC] transfusions in accordance with institutional guidelines) 9.Platelet count greater than or equal to 50× 109/L (equal to 30 × 109/L if myeloma involvement in the bone marrow is > 50%) within 14 days prior to enrollment 10.Creatinine clearance (CrCl) greater than or equal to 15 mL/minute within 7 days prior to enrollment, either measured or calculated using a standard formula (eg, Cockcroft and Gault) Ethical/Other 11.Written informed consent in accordance with local, and institutional guidelines. 12.Women of childbearing potential must have a negative serum pregnancy test within the 7 days prior to study drug administration and a negative urine pregnancy test within the 3 days prior to the first study drug administration. 13.Women of childbearing potential and male subjects who are sexually active with WOCBP must agree to use 2 highly effective methods of contraception during the study and for 30 days following the last dose of study treatment including a male condom.
Exclusion criteria
Disease-related 1. Multiple Myeloma of IgM subtype. 2. Glucocorticoid therapy within 14 days prior to enrollment that equals or exceeds a cumulative dose of 160 mg of dexamethasone. 3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes). 4. Plasma cell leukemia (greater than 2.0 × 109/L circulating plasma cells by standard differential). 5. Waldenstrom macroglobulinemia (WM). 6. Known amyloidosis. 7. Any immunotherapy for myeloma within 21 days prior to enrollment. Concurrent Conditions 8.Pregnant or lactating females 9.Major surgery within 21 days prior to enrollment(unless related to myeloma) 10.Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrollment 11.Known human immunodeficiency virus infection 12.Active hepatitis B or C infection 13.Unstable angina or myocardial infarction within 4 months prior to randomization, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker 14. Pulmonary Hypertension 15.LVEF of less than 40% 16.Uncontrolled hypertension or uncontrolled diabetes 17.Nonhematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas 18.Significant neuropathy (Grades 3–4, or Grade 2 with pain) within 14 days prior to enrollment 19.Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib) 20.Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment 21.Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to enrollment 22.Any other clinically significant medical disease or condition that, in the Investigator’s opinion, may interfere with protocol adherence or a subject’s ability to give informed consent
Outcome results
None listed