Phase II, Single-arm Trial of Carfilzomib, Pomalidomide, and Dexamethasone for Myeloma Patients Who Had Relapsed or Progressed After Carfilzomib, Lenalidomide, and Dexamethasone
Overview
- Phase
- Phase 2
- Intervention
- Carfilzomib 56 MG [Kyprolis]
- Conditions
- Multiple Myeloma
- Sponsor
- Samsung Medical Center
- Enrollment
- 33
- Locations
- 1
- Primary Endpoint
- Overall response rate
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the evaluate the efficacy and safety of administering a combination of carfilzomib, pomalidomide, and dexamethasone in patients with relapsed or advanced multiple myeloma after carfilzomib, lenalidomide, and dexamethasone therapy.
Detailed Description
This study is a phase 2 study in which patients with RRMM under 80 years of age who have been treated with lenalidomide monotherapy for at least 6 months after KRd combination therapy will receive carfilzomib, pomalidomide, and dexamethasone combination therapy. A total of 33 participants are recruited. KPd will be administered until progressive disease or unacceptable toxicities. Participants who discontinued treatment will be followed up for disease status and survival at 2-month intervals. Responses are assessed using the International Myeloma Working Group (IMWG) response criteria and the safety profile is described using NCI-CTCAE v5.0.
Investigators
Kihyun Kim
Principal Investigator
Samsung Medical Center
Eligibility Criteria
Inclusion Criteria
- •Age from 20 to 80 years-old
- •Relapse or progression of multiple myeloma after treatment of carfilzomib/lenalidomide/dexamethasone (KRd)
- •KRd treatment 12 cycles or more and lenalidomide maintenance for at least 6 months or KRd 4-6 cycles followed by ASCT and lenalidomide maintenance for at least 6 months
- •Measurable disease
- •Serum M-protein ≥ 1 g/dL (10 g/L)
- •Urine M-protein ≥ 200 mg/24 hr
- •Serum FLC assay: difference of FLC ≥ 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal (KL ratio \< 0.26 or \> 1.65) if Serum EP or urine EP is not measurable
- •Adequate organ functions
- •Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L
- •Platelets ≥ 50 x 109/L (≥ 30 x 109/L if myeloma involvement is \> 50% in the bone marrow)
Exclusion Criteria
- •Grade 3\~4 non-hematologic toxicity by carfilzomib during the previous carfilzomib treatment
- •Prior therapy with pomalidomide
- •Hypersensitivity to thalidomide or lenalidomide
- •Previous refractoriness to carfilzomib according to the IMWG criteria
- •Myocardial infarct within 6 months, heart failure of NYHA Class III\~IV, uncontrolled ventricular arrhythmia, severe coronary arterial obstructive disease
- •Active infection with 14 days prior to treatment
- •Uncontrolled hypertension (Defined as an average systolic blood pressure \>= 160 mmHg or diastolic \>= 100 mmHg) or diabetes (HbA1c \> 7.0%)
- •HIV, HBV, HCV infection (exception if adequately controlled HBV (undetectable HBV DNA (\< 20 IU/mL or concurrent use of an anti-viral agent), HCV)
- •Severe or uncontrolled medical conditions, laboratory abnormalities, or psychiatric disorders that may preclude the participation of the study by the physician's discretion
- •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
Arms & Interventions
A study of carfilzomib, pomalidomide and dexamethasone administration after KRd administration
Patients with RRMM who progressed after receiving lenalidomide monotherapy for at least 6 months after administration of KRd will receive KPD therapy every 4 weeks until disease progression.
Intervention: Carfilzomib 56 MG [Kyprolis]
A study of carfilzomib, pomalidomide and dexamethasone administration after KRd administration
Patients with RRMM who progressed after receiving lenalidomide monotherapy for at least 6 months after administration of KRd will receive KPD therapy every 4 weeks until disease progression.
Intervention: Pomalidomide
A study of carfilzomib, pomalidomide and dexamethasone administration after KRd administration
Patients with RRMM who progressed after receiving lenalidomide monotherapy for at least 6 months after administration of KRd will receive KPD therapy every 4 weeks until disease progression.
Intervention: Dexamethasone
Outcomes
Primary Outcomes
Overall response rate
Time Frame: assessed for approximately 3 years after administration
percentage of patients who achieve at least partial response
Secondary Outcomes
- Duration of response(assessed for approximately 3 years after administration)
- Incidence of treatment-emergent adverse events(assessed for approximately 3 years after administration)
- Complete response rate(assessed for approximately 3 years after administration)
- Overall survival(assessed for approximately 3 years after administration)
- Progression free survival rate(assessed for approximately 3 years after administration)
- Time to response(assessed for approximately 3 years after administration)
- Minimal residual disease negativity(up to 3 years)