Phase II Study of Carfilzomib, Pomalidomide, and Dexamethasone for Myeloma Patients Who Had Relapsed or Progressed After Carfilzomib, Lenalidomide, and Dexamethasone (KMM2002)

Phase II, Single-arm Trial of Carfilzomib, Pomalidomide, and Dexamethasone for Myeloma Patients Who Had Relapsed or Progressed After Carfilzomib, Lenalidomide, and Dexamethasone

The purpose of this study is to evaluate the evaluate the efficacy and safety of administering a combination of carfilzomib, pomalidomide, and dexamethasone in patients with relapsed or advanced multiple myeloma after carfilzomib, lenalidomide, and dexamethasone therapy.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Carfilzomib 56 MG [Kyprolis]; Drug: Pomalidomide; Drug: Dexamethasone

Detailed Description

This study is a phase 2 study in which patients with RRMM under 80 years of age who have been treated with lenalidomide monotherapy for at least 6 months after KRd combination therapy will receive carfilzomib, pomalidomide, and dexamethasone combination therapy.

A total of 33 participants are recruited.

KPd will be administered until progressive disease or unacceptable toxicities.

Participants who discontinued treatment will be followed up for disease status and survival at 2-month intervals.

Responses are assessed using the International Myeloma Working Group (IMWG) response criteria and the safety profile is described using NCI-CTCAE v5.0.

• Study Type: Interventional
• Enrollment (Anticipated): 33
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kihyun Kim, 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
    • Contact: Bobae Lee; Phone Number: 82-2-2148-7690; Email: bb.lee@sbri.co.kr
    • Principal Investigator: Kihyun Kim, Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age from 20 to 80 years-old
2. Relapse or progression of multiple myeloma after treatment of carfilzomib/lenalidomide/dexamethasone (KRd)
3. KRd treatment 12 cycles or more and lenalidomide maintenance for at least 6 months or KRd 4-6 cycles followed by ASCT and lenalidomide maintenance for at least 6 months

4. Measurable disease

   • Serum M-protein ≥ 1 g/dL (10 g/L)
   • Urine M-protein ≥ 200 mg/24 hr
   • Serum FLC assay: difference of FLC ≥ 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal (KL ratio < 0.26 or > 1.65) if Serum EP or urine EP is not measurable

5. Adequate organ functions

   • 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 or Serum Cr <3.0 g/dL
   • Serum Bilirubin ≤ 1.5 x ULN
   • AST and ALT ≤ 3 x ULN
6. Eastern Cooperative Oncology Group performance scale 0~2
7. Life expectancy longer than 3 months
8. Written informed consent
9. Prior therapy with bortezomib

10. Patients who meet the following criteria

    • If a woman of childbearing age

      • Women who are willing to use two reliable methods of contraception from 4 weeks prior to administration of study drug, while receiving, temporarily suspending administration, and 4 weeks after administration of the study drug.
      • Women who have a negative pregnancy test with a minimum sensitivity of 25 IU/mL under medical management

    • For men Men who agree to abstain from absolute abstinence or use a proper method of contraception for the entire duration of treatment and 28 days after the last dose

      • Women of childbearing age Women who have not undergone hysterectomy or bilateral oophorectomy, women who have not undergone spontaneous menopause for at least 24 consecutive months (i.e., menstruate at any time during the last 24 months. However, amenorrhea after chemotherapy does not exclude the possibility of pregnancy).
      • Proper method of contraception
    • Very effective way Intrauterine device, hormone therapy (hormone implant, intrauterine system releasing levonorgestrel, medroxyprogesterone acetate depot injection, tablets containing progesterone to inhibit ovulation), tubal ligation, varicose veins in men
    • Effective way Men's condom use, diaphragm method, cervical cap

Exclusion Criteria:

1. Grade 3~4 non-hematologic toxicity by carfilzomib during the previous carfilzomib treatment
2. Prior therapy with pomalidomide
3. Hypersensitivity to thalidomide or lenalidomide
4. Previous refractoriness to carfilzomib according to the IMWG criteria
5. Myocardial infarct within 6 months, heart failure of NYHA Class III~IV, uncontrolled ventricular arrhythmia, severe coronary arterial obstructive disease
6. Active infection with 14 days prior to treatment
7. Uncontrolled hypertension (Defined as an average systolic blood pressure >= 160 mmHg or diastolic >= 100 mmHg) or diabetes (HbA1c > 7.0%)
8. HIV, HBV, HCV infection (exception if adequately controlled HBV (undetectable HBV DNA (< 20 IU/mL or concurrent use of an anti-viral agent), HCV)
9. Severe or uncontrolled medical conditions, laboratory abnormalities, or psychiatric disorders that may preclude the participation of the study by the physician's discretion
10. 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
11. 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.
12. Pregnant or nursing women
13. Waldenstroem's macroglobulinemia, POEMS syndrome, or plasma cell leukemia, light chain amyloidosis
14. LV ejection fraction < 40%

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: A study of carfilzomib, pomalidomide and dexamethasone administration after KRd administration; Patients with RRMM who progressed after receiving lenalidomide monotherapy for at least 6 months after administration of KRd will receive KPD therapy every 4 weeks until disease progression.	Drug: Carfilzomib 56 MG [Kyprolis]; Carfilzomib 56 mg/m2 (Day1, 8, 15) (Cycle1 Day1, 20 mg/m2); Drug: Pomalidomide; Pomalidomide 4 mg per os (Day1-21); Drug: Dexamethasone; Dexamethasone 40 mg (D1, 8, 15, 22) (20 mg for patients ≥ 75 years old)

What is the study measuring?

Primary 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate	percentage of patients who achieve complete response	assessed for approximately 3 years after administration
Progression free survival rate	percentage of patients who are disease free or alive	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
Incidence of treatment-emergent adverse events	Safety profiles of carfilzomib, pomalidomide, and dexamethasone for myeloma patients who had relapsed or progressed	assessed for approximately 3 years after administration
Minimal residual disease negativity	The specimen is bone marrow aspirate, and it should be free of clonal plasma cells by examination by the NGF (next-generation flow) method. At this time, the test should be performed according to the EuroFlow standard operation procedure for MRD detection in MM, and the minimum sensitivity should be10 to the 5th power or higher.	up to 3 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2021
• Primary Completion (Anticipated): June 30, 2024
• Study Completion (Anticipated): June 30, 2024

Study Registration Dates

• First Submitted: August 18, 2022
• First Submitted That Met QC Criteria: August 19, 2022
• First Posted (Actual): August 22, 2022

Study Record Updates

• Last Update Posted (Actual): August 22, 2022
• Last Update Submitted That Met QC Criteria: August 19, 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; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Pomalidomide
• Other Study ID Numbers: SMC-2021-03-147

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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