Carfilzomib, Oral Cyclophosphamide, and Dexamethasone for RRMM

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Very good partial response [Срок оценки: from the first date of KCd to the day 30 after KCd stop date]

Вторичные конечные точки (6)

• Overall response [Срок оценки: from the first date of KCd to the day 30 after KCd stop date]
• Progression-free survival [Срок оценки: 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 [Срок оценки: from the first date of KCd until the date of death from any cause, assessed up to 48 months]
• Duration of response [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: from the first date of KCd to day 30 after KCd stop date]

Критерии участия

Критерии включения

• 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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT05909826 · DAUHIRB-23-038

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗