Carfilzomib, Lenalidomide, and Dexamethasone Re-induction Followed by the 2nd ASCT in Multiple Myeloma Patients Relapsed After the 1st ASCT

Multiple Myeloma Clinical Trial

— KMM1911  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05497102
• Other study ID #: SMC 2019-12-037
• Status: Recruiting
• Phase: Phase 2
• Start date: November 8, 2021
• Est. completion date: December 2025

Study information

• Verified date: August 2022
• Source: Samsung Medical Center
• Contact: Kihyun Kim, M.D., Ph.D
• Phone: 82-2-2148-7333
• Email: kihyunk.kim[@]samsung.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 58
• Est. completion date: December 2025
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Lenalidomide maintenance
Lenalidomide maintenance after carfilzomib, lenalidomide, and dexamethasone re-induction followed by the 2nd ASCT.

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Samsung Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	2-year progression free survival rate	percentage of patients who are disease free or alive at 2-years	2-years after the written consent
Secondary	Complete response rate after KRd #6	percentage of patients who achieve complete response	total 6 cycles (each cycle is 28 days) of induction therapy
Secondary	Complete response rate after ASCT	percentage of patients who achieve complete response	at the time of 2nd ASCT (within 60 days after ASCT)
Secondary	Overall response rate	percentage of patients who achieve at least partial response	assessed for approximately 3 years after administration
Secondary	Time to response	from the time of written consent to the time of achieving at least partial response	assessed for approximately 3 years after administration
Secondary	Duration of response	from the time of achieving at least partial response to the time of progressive disease	assessed for approximately 3 years after administration
Secondary	Overall survival	from the time of written consent to the time of death or last follow-up	assessed for approximately 3 years after administration
Secondary	Safety of KRd induction therapy, 2nd ASCT, and lenalidomide maintenance therapy	treatment-emergent adverse events	assessed for approximately 2 years during administration
Secondary	Rate of the successful stem cell harvest	percentage of patients who collected cluster of differentiation(CD34+) hematopoietic stem cells > 2 x 10^6 cells/kg	total 6 cycles (each cycle is 28 days) of induction therapy