Carfilzomib in Combination With Dexamethasone (Kd) in Chinese Patients With Relapsed & Refractory Multiple Myeloma

NCT ID: NCT03029234

Last Updated: 2022-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 126 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-31
• Study Completion Date: 2021-06-04

Brief Summary

The purpose of this study is to evaluate the safety, tolerability and overall response rate of carfilzomib in combination with dexamethasone for the treatment of multiple myeloma in China.

Conditions

Relapsed and Refractory Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carfilzomib with Dexamethasone

Participants will receive carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter).

Participants will also receive 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle.

Participants will receive treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, non-compliance, or intercurrent illness or worsening of a chronic condition, whichever occurs first.

Group Type: EXPERIMENTAL

Dexamethasone

Intervention Type: DRUG

20 mg intravenous (IV) or oral dexamethasone on days 1, 2, 8, 9, 15, 16, 22, and 23 in 28-day cycles.

Carfilzomib

Intervention Type: DRUG

Infusion of IV carfilzomib on days 1, 2, 8, 9, 15 and 16 in each 28-day cycle.

Interventions

Dexamethasone

20 mg intravenous (IV) or oral dexamethasone on days 1, 2, 8, 9, 15, 16, 22, and 23 in 28-day cycles.

Intervention Type: DRUG

Carfilzomib

Infusion of IV carfilzomib on days 1, 2, 8, 9, 15 and 16 in each 28-day cycle.

Intervention Type: DRUG

Other Intervention Names

Kyprolis

Eligibility Criteria

Inclusion Criteria

Inclusion Criteria: - Multiple myeloma - Subjects must have measurable disease, defined as one or more of the following: -- Serum M-protein ≥ 1 g/dL -- Urine M-protein ≥ 200 mg/24 hours -- In subjects without measurable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal κ/λ ratio - Subjects must have been responsive (ie, achieved a minimal response [MR] or better) to at least one of their prior treatment regimens - Refractory to the most recently received therapy. Refractory disease defined as ≤ 25% response to, or progressing during therapy or within 60 days after completion of therapy - Subjects must have received ≥ 2 prior regimens. Induction therapy and stem cell transplant (± maintenance) will be considered as 1 regimen - Subjects must have received prior treatment with bortezomib and an immunomodulatory drug - Subjects must have received an alkylating agent or anthracycline alone or in combination with other myeloma treatments (this may include high dose melphalan as part of the conditioning regimen prior to a stem cell transplant) - Males and females ≥ 18 years of age - Life expectancy of more than 3 months - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 - Adequate hepatic function, with bilirubin < 2.0 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 times the ULN - Absolute neutrophil count (ANC) ≥ 1,000/mm³, hemoglobin ≥ 8.0 g/dL, and platelet count ≥ 50,000/mm³ • Subjects should not have received platelet transfusions for at least 1 week prior to obtaining the screening platelet count • Screening ANC should be independent of granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF) support for ≥ 1 week and pegylated G-CSF for ≥ 2 weeks • Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed; however, most recent RBC transfusion may not have been done within 7 days prior to obtaining screening hemoglobin - Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/min. Calculated CrCl should be performed by using a widely accepted equation (eg, the Cockcroft and Gault equation): ([140 - Age] × Mass [kg] / [72 × Creatinine mg/dL]). Multiply the result by 0.85 if the subject is female. - Left ventricular ejection fraction (LVEF) ≥ 40%; 2-dimensional transthoracic echocardiogram (ECHO) is the preferred method of evaluation; multiple gated acquisition scan (MUGA) is acceptable if ECHO is not available - Written informed consent in accordance with federal, local, and institutional guidelines - Female subjects of child-bearing potential (FCBP) must have a negative serum pregnancy test within 21 days prior to enrollment and agree to use an effective method of contraception during and for 30 days following last dose of carfilzomib. This protocol defines a FCBP as a sexually mature woman who: 1) has not undergone a hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, or 2) has not been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months) - Male subjects must use an effective barrier method of contraception during the study and for 3 months following the last dose of carfilzomib if sexually active with a FCBP. Male subjects must not donate sperm during treatment and for an additional 90 days after last dose of carfilzomib. Male subjects with pregnant partners must practice sexual abstinence or use a condom during vaginal sex.

Exclusion Criteria

Exclusion Criteria: - Waldenström's macroglobulinemia or immunoglobulin M (IgM) multiple myeloma - Subjects who failed to achieve at least a confirmed MR on any of their prior regimens - Subjects with non-secretory multiple myeloma, defined as < 1 g/dL M-protein in serum and < 200 mg/24 hour M-protein in urine and SFLC ≤ 100 mg/L (involved light chain) - Glucocorticoid therapy (prednisone > 10 mg/day or equivalent) within 3 weeks prior to Cycle 1 Day 1 - POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) - Plasma cell leukemia (> 2.0 × 10⁹/L circulating plasma cells by standard differential) - Chemotherapy with approved or investigative anticancer therapeutics including steroid therapy within the 3 weeks prior to Cycle 1 Day 1 - Radiation therapy or immunotherapy in the 4 weeks prior to Cycle 1 Day 1; localized radiation therapy within 1 week prior to Cycle 1 Day 1 - Participation in an investigational therapeutic study within 3 weeks or within 5 drug half-lives (T½) prior to Cycle 1 Day 1, whichever time is greater - Prior treatment with carfilzomib - Major surgery within 3 weeks before Cycle 1 Day 1 - Congestive heart failure (CHF; New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months - Uncontrolled hypertension (a sustained systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg) - Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to Cycle 1 Day 1 - Known human immunodeficiency virus (HIV) seropositive, hepatitis C infection, and/or hepatitis B (except for patients with hepatitis B surface antigen or core antibody receiving and responding to antiviral therapy directed at hepatitis B: these patients are allowed) - Non-hematologic malignancy within the past 3 years except: -- Adequately treated basal cell or squamous cell skin cancer, -- Carcinoma in situ of the cervix, or -- Prostate cancer < Gleason Score 6 with stable prostate-specific antigen - Subjects with treatment-related myelodysplastic syndrome - Significant neuropathy (Grade 3, 4, or Grade 2 with pain) at the time of baseline evaluation - Subjects in whom the required program of fluid hydration is contraindicated, eg, due to pre-existing pulmonary, cardiac, or renal impairment - Subjects with known or suspected amyloidosis - Subjects with pleural effusions requiring thoracentesis - Subjects with ascites requiring paracentesis - Any clinically significant medical disease or condition, that in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent - Female subjects who are pregnant or lactating, or planning to become pregnant during treatment and for an additional 30 days after discontinuing carfilzomib. - Serious psychiatric or medical conditions that could interfere with treatment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Onyx Therapeutics, Inc.

INDUSTRY

Sponsor Role: collaborator

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Beijing Chao Yang Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Peking University Third Hospital

Beijing, Beijing Municipality, China

Fujian Medical University Union Hospital

Fuzhou, Fujian, China

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, China

Guangzhou First Peoples Hospital

Guangzhou, Guangdong, China

Henan Cancer Hospital

Zhengzhou, Henan, China

The Central Hospital of Wuhan

Wuhan, Hubei, China

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

The First Hospital of Jilin University

Changchun, Jilin, China

The First Hospital of China Medical University

Shenyang, Liaoning, China

Zhongshan Hospital Fudan University

Shanghai, Shanghai Municipality, China

West China Hospital, Sichuang University

Chengdu, Sichuan, China

Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, China

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, China

The First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

Peking Union Medical College Hospital

Beijing, , China

Shanghai Changzheng Hospital

Shanghai, , China

Countries

China

References

Du J, Fang B, Li J, Jin J, Wang S, Zou D, Cai Z, Wang H, Hu J, Li W, Fu C, Shao Z, Xia Z, Liu P, Niu T, Tang ET, Kimball AS, Hou J, Chen W. A study of carfilzomib and dexamethasone in patients with relapsed and refractory multiple myeloma in China. Int J Hematol. 2021 Mar;113(3):422-429. doi: 10.1007/s12185-020-03044-z. Epub 2021 Jan 3.

Reference Type: BACKGROUND

PMID: 33389656 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

CFZ005

Identifier Type: OTHER

Identifier Source: secondary_id

20140242

Identifier Type: -

Identifier Source: org_study_id