Carfilzomib, Oral Cyclophosphamide, and Dexamethasone for RRMM

Phase 2Not Yet RecruitingNCT05909826

Dong-A University Hospital49 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Myeloma in Relapse Multiple Myeloma, Refractory

Interventions

CarfilzomibDRUG

70 mg/m2 IV days 1, 8 and 15, every 4 weeks

CyclophosphamideDRUG

50 mg PO days 1 to 21, every 4 weeks

DexamethasoneDRUG

40mg PO or IV days 1, 8, 15, and 22, every 4 weeks

Eligibility

Sex: ALLMin age: 19 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Very good partial response

Reduction of serum M-protein \> 90%

Time frame: from the first date of KCd to the day 30 after KCd stop date

Secondary Outcomes

Overall response

sCR+CR+VGPR+PR

Time frame: from the first date of KCd to the day 30 after KCd stop date

Progression-free survival

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

Overall survival

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

Duration of response

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

Time to response

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

Safety profile

Adverse events after KCd

Time frame: from the first date of KCd to day 30 after KCd stop date

Central Contacts

Ji Hyun Lee, MD, Ph.D

CONTACT

82-51-240-2915 hidrleejh@dau.ac.kr

Data from ClinicalTrials.gov

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