Multiple Myeloma
Conditions
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.
Interventions
Lenalidomide maintenance after carfilzomib, lenalidomide, and dexamethasone re-induction followed by the 2nd ASCT.
Sponsors
Samsung Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age 20\ 70 2. Progressive disease after 1st ASCT 3. Duration of response after 1st ASCT \> 12 months 4. 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) 5. 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 * Creatinine clearance ≥ 30 mL/minute * Serum Bilirubin ≤ 1.5 x upper limit of normal * Aspartate aminotransferase(AST) and Alanine aminotransferase(ALT) ≤ 3 x upper limit of normal 6. Eastern Cooperative Oncology Group performance scale 0\ 2 7. Survival expectancy \> 3 months 8. Adequately controlled hepatitis B(HBV) & hepatitis C(HCV) 9. Written informed consent 10. Optimal contraceptions
Exclusion criteria
1. Prior refractoriness or intolerance to carfilzomib 2. Prior refractoriness or intolerance to lenalidomide/dexamethasone 3. Any treatment after progressive disease after 1st ASCT. High-dose dexamethasone or palliative radiation is permitted. 4. Waldenstroem's macroglobulinemia, POEMS syndrome, or plasma cell leukemia 5. Pregnant or nursing lactating women 6. Myocardial infarct within 6 months, heart failure of New York Heart Association(NYHA) Class III\ IV, uncontrolled ventricular arrhythmia, severe coronary arterial obstructive disease 7. Uncontrolled hypertension (Defined as an average systolic blood pressure \>= 160 mmHg or diastolic \>= 100 mmHg) or diabetes 8. Grade 3\ 4 neuropathy 9. HIV infection 10. Severe or uncontrolled medical conditions, laboratory abnormalities, or psychiatric disorders that may preclude the participation of the study by the physician's discretion 11. 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 12. Diagnosis of other malignant disease other than myeloma within 5 year. Exceptions are properly treated non-melanomatous skin cancers, cervical intraepithelial neoplasia, prostate cancer that do not require treatment, or properly excised well-differentiated thyroid cancers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2-year progression free survival rate | 2-years after the written consent | percentage of patients who are disease free or alive at 2-years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response | assessed for approximately 3 years after administration | from the time of achieving at least partial response to the time of progressive disease |
| Overall survival | assessed for approximately 3 years after administration | from the time of written consent to the time of death or last follow-up |
| Complete response rate after KRd #6 | total 6 cycles (each cycle is 28 days) of induction therapy | percentage of patients who achieve complete response |
| Time to response | assessed for approximately 3 years after administration | from the time of written consent to the time of achieving at least partial response |
| Overall response rate | assessed for approximately 3 years after administration | percentage of patients who achieve at least partial response |
| Safety of KRd induction therapy, 2nd ASCT, and lenalidomide maintenance therapy | assessed for approximately 2 years during administration | treatment-emergent adverse events |
| Rate of the successful stem cell harvest | total 6 cycles (each cycle is 28 days) of induction therapy | percentage of patients who collected cluster of differentiation(CD34+) hematopoietic stem cells \> 2 x 10\^6 cells/kg |
| Complete response rate after ASCT | at the time of 2nd ASCT (within 60 days after ASCT) | percentage of patients who achieve complete response |
Countries
South Korea
Contacts
Primary ContactKihyun Kim, M.D., Ph.D
Outcome results
None listed