Carfilzomib, Oral Cyclophosphamide, and Dexamethasone for RRMM

Multiple Myeloma in Relapse Clinical Trial

— KMM-KCd  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05909826
• Other study ID #: DAUHIRB-23-038
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 1, 2023
• Est. completion date: June 30, 2027

Study information

• Verified date: June 2023
• Source: Dong-A University Hospital
• Contact: Ji Hyun Lee, MD, Ph.D
• Phone: 82-51-240-2915
• Email: hidrleejh[@]dau.ac.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 49
• Est. completion date: June 30, 2027
• Est. primary completion date: June 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma in Relapse
• Multiple Myeloma, Refractory
• Neoplasms, Plasma Cell

Intervention

Drug:
• Carfilzomib
70 mg/m2 IV days 1, 8 and 15, every 4 weeks
• Cyclophosphamide
50 mg PO days 1 to 21, every 4 weeks
• Dexamethasone
40mg PO or IV days 1, 8, 15, and 22, every 4 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Dong-A University Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Very good partial response	Reduction of serum M-protein > 90%	from the first date of KCd to the day 30 after KCd stop date
Secondary	Overall response	sCR+CR+VGPR+PR	from the first date of KCd to the day 30 after KCd stop date
Secondary	Progression-free survival	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
Secondary	Overall survival	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
Secondary	Duration of response	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
Secondary	Time to response	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
Secondary	Safety profile	Adverse events after KCd	from the first date of KCd to day 30 after KCd stop date