Carfilzomib, Lenalidomide, and Dexamethasone Re-induction Followed by the 2nd ASCT in Multiple Myeloma Patients Relapsed After the 1st ASCT (KMM1911)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Lenalidomide maintenance

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.

• Study Type: Interventional
• Enrollment (Anticipated): 58
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kihyun Kim, M.D., Ph.D; Phone Number: 82-2-2148-7333; Email: kihyunk.kim@samsung.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Samsung Medical Center
    • Principal Investigator: Kihyun Kim
    • Contact: Hyunju Park; Phone Number: 82-2-2148-7333; Email: hj9734.park@sbri.co.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Lenalidomide maintenance; Lenalidomide maintenance after carfilzomib, lenalidomide, and dexamethasone re-induction followed by the 2nd ASCT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	percentage of patients who achieve at least partial response	assessed for approximately 3 years after administration
Overall survival	from the time of written consent to the time of death or last follow-up	assessed for approximately 3 years after administration
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
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
Complete response rate after KRd #6	percentage of patients who achieve complete response	total 6 cycles (each cycle is 28 days) of induction therapy
Complete response rate after ASCT	percentage of patients who achieve complete response	at the time of 2nd ASCT (within 60 days after ASCT)
Safety of KRd induction therapy, 2nd ASCT, and lenalidomide maintenance therapy	treatment-emergent adverse events	assessed for approximately 2 years during administration
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

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: Kihyun Kim, M.D., Ph.D, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2021
• Primary Completion (Anticipated): May 1, 2024
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: July 27, 2022
• First Submitted That Met QC Criteria: August 9, 2022
• First Posted (Actual): August 11, 2022

Study Record Updates

• Last Update Posted (Actual): August 12, 2022
• Last Update Submitted That Met QC Criteria: August 10, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: SMC 2019-12-037

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No