A multicentre single arm study to evaluate the safety and efficacy of carfilzomib-thalidomide-dexamethasone (CarTD) for newly diagnosed transplant-eligible multiple myeloma (TE NDMM) patients refractory to initial bortezomib-based induction therapy (MM17)

Funding

Commercial sector/Industry,Onyx Pharmaceuticals Inc., a subsidiary of Amgen, Inc.

Scientific enquiries

Prof Andrew Spencer

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 cond .... 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.
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Key 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 10 .... 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.
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Key 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 Pati .... 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.
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