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Carfilzomib, Oral Cyclophosphamide, and Dexamethasone for RRMM (KMM-KCd)

Primary Purpose

Multiple Myeloma in Relapse, Multiple Myeloma, Refractory

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Carfilzomib
Cyclophosphamide
Dexamethasone
Sponsored by
Dong-A University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma in Relapse

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Subjects aged 19 years or older ECOG performance status 0 to 2 Diagnosed with multiple myeloma by IMWG criteria Subjects previously treated with 1 or more lines of therapy Subjects previously treated with lenalidomide-based combination or sigle drug therapy Subjects with relapsed and/or refractory multiple myeloma Subjects with measurable disease at the time of treatment initiation serum M protein >=0.5 g/dL, or 24h urine M protein >= 200mg/24h serum free light chain difference >=10mg/dL and abnormal FLC ratio Adequate organ function absolute neutrophil count >= 1.0 x 109/L platelelt count >= 50 x 109/L (plasmacytoma in the bone: >=30 x 109/L) Hb >=8g/dL serum creatinine < 3.0mg/dL or CCR >=15mL/min serum AST and ALT <=3 x ULN serum total bilirubin <= 3 x ULN Subjects able to swallow oral drugs Subjects who had experienced toxicities to previous therapies: resolved from previous toxicities or stabilized of the toxicity to grade 1 Subjects who had received allogenetic stem cell transplantation: no acitve graft-versus-host disease Subjects without clinically relevant bleeding Subjects who have informed consent to the study Females of childbearing potential (FCBP) must be negative to pregnancy testing and give consent to practice contraception before and during the treatment Exclusion Criteria: 1. Subjects who were previously exposed to carfilzomib 1. Subjects who were previously exposed to cyclophosphamide 3. Subjects diagnosed with POEMS SD, Waldenstrom macroglobulinemia, Plasma cell leukemia 4. Subjects with concurrent heart conditions Myocardial infarction within 6 months prior to treatment, New York Heart Association class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, Uncontrolled arrythmias (CVDAE version4 grade 2 or more) or symptomatic EKG abnormalities 12-lead EKG : baseline ATcF > 470msec 2D Echocardiography or MUGA scan : systolic EF < 40% with clinically significant symptoms Uncontrolled hypertension ( with medication: systolic BP >= 160 mmHg or diastolic BP >= 100 mmHg) 5. Chronc obstructive pulmonary disease (FEV1 < 60%), history of asthma within 2 years 6. Surgery under general anesthesia withing 2 weeks 7. Subjects diagnosed with malignancies within 5 years (except for cured skin cancer, cervical cancer, intraepithelial gastrointestinal tract cancer after curative procedures or surgery for more than 3 years) 8. Any other 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 9. Pregnant or breatfeeding subjecs

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Weekly carfilzomib-oral cyclophosphamide-dexamethasone

    Arm Description

    Weekly carfilzomib-oral cyclophosphamide-dexamethasone

    Outcomes

    Primary Outcome Measures

    Very good partial response
    Reduction of serum M-protein > 90%

    Secondary Outcome Measures

    Overall response
    sCR+CR+VGPR+PR
    Progression-free survival
    the time from the first date of KCd to the date of disease progression or death or censored date
    Overall survival
    the time from the first date of KCd to the date of death or censored date
    Duration of response
    the time from the first date of PR to the date of disease progression or death or censord date
    Time to response
    the time from the first date of KCd to the first date of partial response
    Safety profile
    Adverse events after KCd

    Full Information

    First Posted
    February 28, 2023
    Last Updated
    June 8, 2023
    Sponsor
    Dong-A University Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05909826
    Brief Title
    Carfilzomib, Oral Cyclophosphamide, and Dexamethasone for RRMM
    Acronym
    KMM-KCd
    Official Title
    A Phase II Study of Carfilzomib, Oral Cyclophosphamide, and Dexamethasone for Relapsed and/or Refractory Multiple Myeloma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    July 1, 2023 (Anticipated)
    Primary Completion Date
    June 30, 2027 (Anticipated)
    Study Completion Date
    June 30, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Dong-A University Hospital

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This study aims to study the efficacy and safety of oral cyclophosphamide in addition to carfilzomib and dexamethadone for RRMM patients who have been previously exposed to lenalidomide combination therapies.
    Detailed Description
    The survival of multiple myeloma (MM) patients has been improved significantly owing to the adoption of immunomodulatory agents (IMiD) and proteasome inhibitors (PI). However, most of the MM patients finally experience relapse of refractoriness of the disease, of which patients who relapse after bortezomib and lenalidomide have very poor prognosis. Carfilzomib is an irreversible second generation PI which is approved by Korean FDA for RRMM in combination with dexamethasone and/or lenalidomide based on the landmark studies ASPIRE and ENDEAVOR studies. The addition of intravenous cyclophosphamide to carfilzomib has recently showed a promising result for RRMM patients after bortezomib and lenalidomide. In this study, cyclophosphamide 50mg orally will be added to carfilzomib once weekly schedule for 21 days daily every 4 weeks. The rationale for oral metronomic cyclophosphamide is based on previous experimental studies which has shown that it removes CD4+CD25+regulatory T cells preserving T and NK/T cell funtions.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Multiple Myeloma in Relapse, Multiple Myeloma, Refractory

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    49 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Weekly carfilzomib-oral cyclophosphamide-dexamethasone
    Arm Type
    Experimental
    Arm Description
    Weekly carfilzomib-oral cyclophosphamide-dexamethasone
    Intervention Type
    Drug
    Intervention Name(s)
    Carfilzomib
    Other Intervention Name(s)
    Kyprolis
    Intervention Description
    70 mg/m2 IV days 1, 8 and 15, every 4 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Cyclophosphamide
    Other Intervention Name(s)
    Alkyloxan
    Intervention Description
    50 mg PO days 1 to 21, every 4 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Dexamethasone
    Intervention Description
    40mg PO or IV days 1, 8, 15, and 22, every 4 weeks
    Primary Outcome Measure Information:
    Title
    Very good partial response
    Description
    Reduction of serum M-protein > 90%
    Time Frame
    from the first date of KCd to the day 30 after KCd stop date
    Secondary Outcome Measure Information:
    Title
    Overall response
    Description
    sCR+CR+VGPR+PR
    Time Frame
    from the first date of KCd to the day 30 after KCd stop date
    Title
    Progression-free survival
    Description
    the time from the first date of KCd to the date of disease progression or death or censored date
    Time Frame
    from the first date of KCd until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
    Title
    Overall survival
    Description
    the time from the first date of KCd to the date of death or censored date
    Time Frame
    from the first date of KCd until the date of death from any cause, assessed up to 48 months
    Title
    Duration of response
    Description
    the time from the first date of PR to the date of disease progression or death or censord date
    Time Frame
    from the first date of PR to the date of disease progression or death or censord date, which ever came first, assessed up to 48 months
    Title
    Time to response
    Description
    the time from the first date of KCd to the first date of partial response
    Time Frame
    from the first date of KCd to the date of first date of equal or more than partial response, which ever came first, assessed up to 48 months
    Title
    Safety profile
    Description
    Adverse events after KCd
    Time Frame
    from the first date of KCd to day 30 after KCd stop date

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    19 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Subjects aged 19 years or older ECOG performance status 0 to 2 Diagnosed with multiple myeloma by IMWG criteria Subjects previously treated with 1 or more lines of therapy Subjects previously treated with lenalidomide-based combination or sigle drug therapy Subjects with relapsed and/or refractory multiple myeloma Subjects with measurable disease at the time of treatment initiation serum M protein >=0.5 g/dL, or 24h urine M protein >= 200mg/24h serum free light chain difference >=10mg/dL and abnormal FLC ratio Adequate organ function absolute neutrophil count >= 1.0 x 109/L platelelt count >= 50 x 109/L (plasmacytoma in the bone: >=30 x 109/L) Hb >=8g/dL serum creatinine < 3.0mg/dL or CCR >=15mL/min serum AST and ALT <=3 x ULN serum total bilirubin <= 3 x ULN Subjects able to swallow oral drugs Subjects who had experienced toxicities to previous therapies: resolved from previous toxicities or stabilized of the toxicity to grade 1 Subjects who had received allogenetic stem cell transplantation: no acitve graft-versus-host disease Subjects without clinically relevant bleeding Subjects who have informed consent to the study Females of childbearing potential (FCBP) must be negative to pregnancy testing and give consent to practice contraception before and during the treatment Exclusion Criteria: 1. Subjects who were previously exposed to carfilzomib 1. Subjects who were previously exposed to cyclophosphamide 3. Subjects diagnosed with POEMS SD, Waldenstrom macroglobulinemia, Plasma cell leukemia 4. Subjects with concurrent heart conditions Myocardial infarction within 6 months prior to treatment, New York Heart Association class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, Uncontrolled arrythmias (CVDAE version4 grade 2 or more) or symptomatic EKG abnormalities 12-lead EKG : baseline ATcF > 470msec 2D Echocardiography or MUGA scan : systolic EF < 40% with clinically significant symptoms Uncontrolled hypertension ( with medication: systolic BP >= 160 mmHg or diastolic BP >= 100 mmHg) 5. Chronc obstructive pulmonary disease (FEV1 < 60%), history of asthma within 2 years 6. Surgery under general anesthesia withing 2 weeks 7. Subjects diagnosed with malignancies within 5 years (except for cured skin cancer, cervical cancer, intraepithelial gastrointestinal tract cancer after curative procedures or surgery for more than 3 years) 8. Any other 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 9. Pregnant or breatfeeding subjecs
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Ji Hyun Lee, MD, Ph.D
    Phone
    82-51-240-2915
    Email
    hidrleejh@dau.ac.kr
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Sung-Hyun Kim, MD, Ph.D
    Organizational Affiliation
    Dong-A University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Carfilzomib, Oral Cyclophosphamide, and Dexamethasone for RRMM

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