Clinical trial NCT05497102: Carfilzomib, Lenalidomide, and Dexamethasone Re-induction Followed by the 2nd ASCT in Multiple Myeloma Patients Relapsed After the 1st ASCT
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2022-08-11
Enrollment: 58
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 2-year progression free survival rate
timeFrame: 2-years after the written consent
Secondary outcomes:
measure: Complete response rate after KRd #6
timeFrame: total 6 cycles (each cycle is 28 days) of induction therapy
measure: Complete response rate after ASCT
timeFrame: at the time of 2nd ASCT (within 60 days after ASCT)
measure: Overall response rate
timeFrame: assessed for approximately 3 years after administration
measure: Time to response
timeFrame: assessed for approximately 3 years after administration
measure: Duration of response
timeFrame: assessed for approximately 3 years after administration
measure: Overall survival
timeFrame: assessed for approximately 3 years after administration
measure: Safety of KRd induction therapy, 2nd ASCT, and lenalidomide maintenance therapy
timeFrame: assessed for approximately 2 years during administration
measure: Rate of the successful stem cell harvest
timeFrame: total 6 cycles (each cycle is 28 days) of induction therapy
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Samsung Medical Center
name: Kihyun Kim, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References: