None listed
Conditions
Brief summary
The primary purpose of this study is to determine the efficacy and safety of carfilzomib-thalidomide-dexamethasone (CarTD) therapy for newly diagnosed transplant-eligible multiple myeloma (NDMM) patients who did not respond adequately to initial bortezomib-based therapy. Who is it for? You may be eligible to join this study if you are aged over 18 years, have been diagnosed with symptomatic NDMM as per International Myeloma Working Group (IMWG) criteria, are eligible for high-dose melphalan conditioned autologous stem cell transplant (ASCT) and failed to achieve a minimum response or partial response on 2 or 4 cycles of prior bortezomib-based induction therapy respectively. Study details Enrolled participants will first undergo 4 x 4-week cycles of salvage CarTD therapy, followed by an additional 2 cycles if they do not achieve a stringent complete response. Participants will then receive melphalan-conditioned ASCT, followed by 2 cycles of consolidation CarTD therapy. Patients will be monitored for myeloma response and safety and tolerability of CarTD therapy using blood samples, and the assessment of toxicities (adverse event review) as well as for disease progression and survival information for up to 3 years following the completion of treatment. It is hoped that the findings of this trial will provide an evaluation of the efficacy and safety of CarTD salvage and consolidation therapy in multiple myeloma patients who do not respond to the standard care bortezomib-based therapy.
Interventions
SALVAGE: Carfilzomib will be given by IV infusion over 30 minutes on Days 1, 2, 8, 9, 15, 16 of each 4-week cycle for 4 cycles. Carfilzomib 20 mg/m2 will be delivered on Cycle 1 Day 1 and 2 and then escalated to 56 mg/m2 from Cycle 1 Day 8 onwards. Thalidomide will be given continuously at a starting dose of 100mg oral daily starting on Day 1, Cycle 1 for the duration of the cycle. Dexamethasone will be given at a dose of 20mg orally on days 1, 2, 8, 9, 15 and 16 of each 4 week cycle prior to ca
SALVAGE: Carfilzomib will be given by IV infusion over 30 minutes on Days 1, 2, 8, 9, 15, 16 of each 4-week cycle for 4 cycles. Carfilzomib 20 mg/m2 will be delivered on Cycle 1 Day 1 and 2 and then escalated to 56 mg/m2 from Cycle 1 Day 8 onwards. Thalidomide will be given continuously at a starting dose of 100mg oral daily starting on Day 1, Cycle 1 for the duration of the cycle. Dexamethasone will be given at a dose of 20mg orally on days 1, 2, 8, 9, 15 and 16 of each 4 week cycle prior to carfilzomib dosing. After 4 cycles of Car-TD Patients will undergo full disease re-evaluation and patients with less than stringent CR will receive an additional 2 cycles of car-TD and then proceed to a G-CSF stimulated PBSC collection. If <2million/kg CD34+ cells are available for ASCT the patient will be withdrawn from the study. Patients with sCR after 4 cycles of Car-TD will proceed directly to a G-CSF mobilised PBSC collection for ASCT, there is no time period intended prior to ASCT. Patients will go to ASCT if eligible to do so with no time period prior to ASCT intended. Autologous stem cell transplant (ASCT): All patients with >=2 million/kg CD34 cells available will then receive a melphalan 200mg/m2 conditioned ASCT as per standard institutional practice. CONSOLIDATION: Commencing at 3 months post-ASCT patients without evidence of disease progression will receive a further 2 cycles of carfilzomib as described above. Thalidomide will be given continuously at a starting dose of 100mg daily starting on day 1 of the first cycle of carfilzomib consolidation and continued for a maximum of 12 months. Dexamethasone will be given at a dose of 20mg on days 1, 2, 8, 9, 15, 16 of each 4-week cycle of carfilzomib consolidation prior to carfilzomib dosing and then revert to a dose of 40mg weekly in combination with ongoing thalidomide to a maximum of 12 months. All dosing is recorded by hospital staff. Drug accountability logs will be used by the hospital staff.
Sponsors
Australiasian Leukaemia and Lymphoma Group
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Male and Female patients, >17 years of age. Symptomatic NDMM as per IMWG criteria. Eligible for high-dose melphalan conditioned ASCT. Failed to achieve at least a minimal response (MR) with a minimum of 2 cycles of a prior bortezomib-based induction therapy or a partial response (PR) with a minimum of 4 cycles of a prior bortezomib-based induction therapy. Adequate liver function (total bilirubin < 1.5 ULN, ALT < 2.5x ULN) unless considered secondary to MM. Absolute neutrophil count > = 1.0 x 109/L within one week of starting therapy. Platelet count > = 50 x 109/L (>= 30 x 109/L if MM involvement in the marrow is greater than 50%) within one week of starting therapy, patients should not have received platelet transfusions within one week of the screening platelet count. Hb >= 80g/L, red cell transfusions as per institutional protocol are allowed. Subject must have LVEF >= 50% determined by 2-D transthoracic echocardiogram (ECHO) or Multigated Acquisition Scan (MUGA). Has provided written informed consent. Women of childbearing potential must have a negative serum pregnancy test within the 72 hours prior to the first study drug administration. 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
Patients who have had myocardial infarction within 6 months prior to enrolment, or NYHA (New York Hospital Association) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities Other uncontrolled intercurrent illness including, but not limited to, severe active infection, or psychiatric illness/social situations that would limit compliance with study requirements Patients with myelodysplastic syndrome. Known history of allergy to Captisol (registered trademark) (a cyclodextrin derivative used to solubilise carfilzomib) Patients with contraindication to dexamethasone. Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs, or intolerance to hydration due to pre-existing pulmonary or cardiac impairment. Women who are pregnant or lactating. Active Hepatitis B or Hepatitis C. HIV infection, other immunosuppressive therapy or autoimmune disease Prior diagnosis of cancer that was: more than 5 years prior to current diagnosis with subsequent evidence of disease recurrence or clinical expectation of recurrence is greater than 10% within 5 years of current diagnosis with the exception of successfully treated basal cell or squamous cell skin carcinoma or carcinoma in situ of the cervix Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. This condition must be discussed with the patient prior to signing consent and registration in the trial.
Outcome results
None listed