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

June 8, 2023 updated by: Sung-Hyun Kim, Dong-A University Hospital

A Phase II Study of Carfilzomib, Oral Cyclophosphamide, and Dexamethasone for Relapsed and/or Refractory Multiple Myeloma

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

49

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Subjects aged 19 years or older
  2. ECOG performance status 0 to 2
  3. Diagnosed with multiple myeloma by IMWG criteria
  4. Subjects previously treated with 1 or more lines of therapy
  5. Subjects previously treated with lenalidomide-based combination or sigle drug therapy
  6. Subjects with relapsed and/or refractory multiple myeloma

  7. 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

  8. 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
  9. Subjects able to swallow oral drugs
  10. Subjects who had experienced toxicities to previous therapies: resolved from previous toxicities or stabilized of the toxicity to grade 1
  11. Subjects who had received allogenetic stem cell transplantation: no acitve graft-versus-host disease
  12. Subjects without clinically relevant bleeding
  13. Subjects who have informed consent to the study
  14. 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Weekly carfilzomib-oral cyclophosphamide-dexamethasone
Drug: Carfilzomib
70 mg/m2 IV days 1, 8 and 15, every 4 weeks
Other Names:
  • Kyprolis
Drug: Cyclophosphamide
50 mg PO days 1 to 21, every 4 weeks
Other Names:
  • Alkyloxan
Drug: Dexamethasone
40mg PO or IV days 1, 8, 15, and 22, every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Very good partial response
Time Frame: from the first date of KCd to the day 30 after KCd stop date
Reduction of serum M-protein > 90%
from the first date of KCd to the day 30 after KCd stop date

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response
Time Frame: from the first date of KCd to the day 30 after KCd stop date
sCR+CR+VGPR+PR
from the first date of KCd to the day 30 after KCd stop date
Progression-free survival
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
the time from the first date of KCd to the date of disease progression or death or censored date
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
Overall survival
Time Frame: from the first date of KCd until the date of death from any cause, assessed up to 48 months
the time from the first date of KCd to the date of death or censored date
from the first date of KCd until the date of death from any cause, assessed up to 48 months
Duration of response
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
the time from the first date of PR to the date of disease progression or death or censord date
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
Time to 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
the time from the first date of KCd to the first date of partial response
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
Safety profile
Time Frame: from the first date of KCd to day 30 after KCd stop date
Adverse events after KCd
from the first date of KCd to day 30 after KCd stop date

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dong-A University Hospital

Investigators

  • Principal Investigator: Sung-Hyun Kim, MD, Ph.D, Dong-A University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2023

Primary Completion (Estimated)

June 30, 2027

Study Completion (Estimated)

June 30, 2027

Study Registration Dates

First Submitted

February 28, 2023

First Submitted That Met QC Criteria

June 8, 2023

First Posted (Estimated)

June 19, 2023

Study Record Updates

Last Update Posted (Estimated)

June 19, 2023

Last Update Submitted That Met QC Criteria

June 8, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DAUHIRB-23-038

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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