Carfilzomib, Oral Cyclophosphamide, and Dexamethasone for RRMM

NCT ID: NCT05909826

Last Updated: 2023-06-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-01
• Study Completion Date: 2027-06-30

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.

Conditions

Multiple Myeloma in Relapse; Multiple Myeloma, Refractory

Study Design

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

Study Groups

Weekly carfilzomib-oral cyclophosphamide-dexamethasone

Weekly carfilzomib-oral cyclophosphamide-dexamethasone

Group Type: EXPERIMENTAL

Carfilzomib

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

50 mg PO days 1 to 21, every 4 weeks

Dexamethasone

Intervention Type: DRUG

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

Interventions

Carfilzomib

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

Intervention Type: DRUG

Cyclophosphamide

50 mg PO days 1 to 21, every 4 weeks

Intervention Type: DRUG

Dexamethasone

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

Intervention Type: DRUG

Other Intervention Names

Kyprolis; Alkyloxan

Eligibility Criteria

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

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dong-A University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Sung-Hyun Kim

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sung-Hyun Kim, MD, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Dong-A University

Central Contacts

Ji Hyun Lee, MD, Ph.D

Role: CONTACT

hidrleejh@dau.ac.kr

82-51-240-2915

Other Identifiers

DAUHIRB-23-038

Identifier Type: -

Identifier Source: org_study_id