Phase II, Single-arm Trial of Carfilzomib, Lenalidomide, and Dexamethasone Re-induction Followed by the 2nd ASCT in Multiple Myeloma Patients Relapsed After the 1st ASCT
Overview
- Phase
- Phase 2
- Intervention
- Lenalidomide maintenance
- Conditions
- Multiple Myeloma
- Sponsor
- Samsung Medical Center
- Enrollment
- 58
- Locations
- 1
- Primary Endpoint
- 2-year progression free survival rate
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of salvage treatment with carfilzomib/lenalidomide/dexamethasone (KRD) followed by 2nd autologous stem cell transplantation (ASCT) and lenalidomide maintenance in patients with relapsed myeloma after 1st ASCT.
Detailed Description
This is a single-arm phase II study to assess the efficacy and safety of KRD followed by 2nd ASCT - lenalidomide maintenance for 18 months in patients with relapsed multiple myeloma after 1st ASCT who are 70 years of age or younger. A total of 58 participants will be recruited. As a re-induction therapy 6 cycles of KRD (K, 27mg/m2, D1,2,8,9,15,16; R, 25 mg, D1-21; D, 40mg weekly, every 28 days) will be administered. If a patient achieves at least partial response, 2nd ASCT + lenalidomide 10mg for 18 months will be proceeded. Study will be continued until disease progression, unacceptable toxicity, or completion of pre-planned schedule. Response will be assessed using the International Myeloma Working Group(IMWG) response criteria and the safety profiles will be described using the NCI-CTCAE v5.0. Participants who discontinue therapy will be followed every 3 months for 3 years if they are on subsequent treatment, disease-free or dead.
Investigators
Kihyun Kim
Professor
Samsung Medical Center
Eligibility Criteria
Inclusion Criteria
- •Progressive disease after 1st ASCT
- •Duration of response after 1st ASCT \> 12 months
- •Measurable disease (+)
- •Serum M-protein ≥ 1 g/dL
- •Urine M-protein ≥ 200 mg/24 hr
- •Serum Free Light Chain(FLC) assay: involved FLC level ≥10 mg/dL (serum Free Light Chain ratio is abnormal)
- •Adequate organ function for induction \& ASCT
- •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)
- •Hemoglobin ≥ 8.0 g/dL
Exclusion Criteria
- •Prior refractoriness or intolerance to carfilzomib
- •Prior refractoriness or intolerance to lenalidomide/dexamethasone
- •Any treatment after progressive disease after 1st ASCT. High-dose dexamethasone or palliative radiation is permitted.
- •Waldenstroem's macroglobulinemia, POEMS syndrome, or plasma cell leukemia
- •Pregnant or nursing lactating women
- •Myocardial infarct within 6 months, heart failure of New York Heart Association(NYHA) Class III\~IV, uncontrolled ventricular arrhythmia, severe coronary arterial obstructive disease
- •Uncontrolled hypertension (Defined as an average systolic blood pressure \>= 160 mmHg or diastolic \>= 100 mmHg) or diabetes
- •Grade 3\~4 neuropathy
- •HIV infection
- •Severe or uncontrolled medical conditions, laboratory abnormalities, or psychiatric disorders that may preclude the participation of the study by the physician's discretion
Arms & Interventions
Single arm of Lenalidomide maintenance
\[KRd #1\~6, Every 4 weeks\] D1, 2, 8, 9, 15,16 Carfilzomib 20mg/m2 + 5% dextrose in water 50 mL over 10 mins (From Cycle1Day8 27mg/m2) D1 - 21 Lenalidomide 25mg P.O. D1, 8, 15, 22 Dexamethasone 40mg IV or PO \[Autologous stem cell transplantation phase\] \[Lenalidomide maintenance phase, Every 4 weeks\] D1-28 Lenalidomide 10 mg
Intervention: Lenalidomide maintenance
Outcomes
Primary Outcomes
2-year progression free survival rate
Time Frame: 2-years after the written consent
percentage of patients who are disease free or alive at 2-years
Secondary Outcomes
- Time to response(assessed for approximately 3 years after administration)
- Complete response rate after KRd #6(total 6 cycles (each cycle is 28 days) of induction therapy)
- Complete response rate after ASCT(at the time of 2nd ASCT (within 60 days after ASCT))
- Overall response rate(assessed for approximately 3 years after administration)
- Duration of response(assessed for approximately 3 years after administration)
- Overall survival(assessed for approximately 3 years after administration)
- Safety of KRd induction therapy, 2nd ASCT, and lenalidomide maintenance therapy(assessed for approximately 2 years during administration)
- Rate of the successful stem cell harvest(total 6 cycles (each cycle is 28 days) of induction therapy)