Carfilzomib With Bendamustine and Dexamethasone in Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT02002598
- Lead Sponsor
- Siyang Leng
- Brief Summary
This study is designed to define dose-limiting toxicity and determine preliminary evidence of efficacy of carfilzomib (CFZ) in combination with bendamustine and dexamethasone for patients with newly diagnosed multiple myeloma (MM).
- Detailed Description
Multiple myeloma (MM) is a malignant plasma cell disorder resulting in approximately 11,000 deaths in the United States each year. It is estimated that between 60,000-80,000 people are currently under treatment for refractory or relapsed MM. Prognosis and survival have improved over the last 20 years, but the disease is still universally fatal despite efforts to develop new and more effective chemotherapeutic regimens. Therefore, new regimens need to be developed for patients prior to peripheral blood stem cell transplant and for those unable to tolerate the toxicity of transplant.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
- Age ≥ 18 years.
- Life expectancy ≥ 3 months.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Adequate hepatic function.
- Sufficient Absolute neutrophil count (ANC) within 14 days prior to randomization.
- Sufficient Hemoglobin within 14 days prior to randomization (subjects may be receiving red blood cell (RBC) transfusions in accordance with institutional guidelines).
- Sufficient platelet count 14 days prior to randomization.
- Creatinine Clearance ≥ 30 mL/minute within 7 days prior to randomization.
- Left Ventricular Ejection Fraction ≥ 40%.
- Written informed consent in accordance with federal, local, and institutional guidelines.
- Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception.
- Male subjects must agree to practice contraception.
- Patients must have histologically or cytologically confirmed symptomatic multiple myeloma (MM). Patients should not have previously been treated.
- Prior kyphoplasty, vertebroplasty, local radiation therapy for symptomatic bone lesions (e.g., uncontrolled pain or high risk of pathologic fracture) are permitted.
- Patients are allowed up to two cycles of high dose steroids if needed for symptomatic disease before study enrollment.
- Patients who have had chemotherapy for Multiple Myeloma. Exception: local radiation therapy for symptomatic bone lesions (e.g., uncontrolled pain or high risk of pathologic fracture).
- Patients currently receiving high dose systemic steroids for treatment of Multiple Myeloma in excess of 320mg total dose of dexamethasone or equivalent, patients who received an investigational agent within 5 half-lives of the agent.
- Patients with non-measurable Multiple Myeloma or primary plasma cell leukemia.
- Pregnant or lactating females.
- Major surgery within 21 days prior to enrollment.
- Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrollment.
- Known human immunodeficiency virus (HIV) infection.
- Known active hepatitis B or C infection.
- Unstable angina or myocardial infarction within 4 months prior to enrollment.
- Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment.
- Uncontrolled, non-hematologic malignancy requiring active treatment.
- Patients with known brain metastases (treated or not) will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Significant neuropathy within 14 days prior to randomization.
- Known history of allergy to Captisol, or to other agents in the study.
- Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment.
- Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to enrollment.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CFZ with bendamustine and dexamethasone Bendamustine Subjects will receive Carfilzomib on Days 1, 2, 8, 9, 15, and 16 every 28 days with dose escalation from 27, 36, 45 to 56 mg/ m2 . No matter what target dose the subject will receive, days 1 and 2 doses in the first cycle will always be 20 mg/m2, followed by target dose for all subsequent dates and cycles. Bendamustine will be given IV on days 1 and 2 with dose escalation up to 90 mg/m2 and dexamethasone 20 mg orally or intravenously on 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day cycle. Study treatment will be given until 8 cycles of treatment are completed or until disease progression, whichever comes first. CFZ with bendamustine and dexamethasone Carfilzomib Subjects will receive Carfilzomib on Days 1, 2, 8, 9, 15, and 16 every 28 days with dose escalation from 27, 36, 45 to 56 mg/ m2 . No matter what target dose the subject will receive, days 1 and 2 doses in the first cycle will always be 20 mg/m2, followed by target dose for all subsequent dates and cycles. Bendamustine will be given IV on days 1 and 2 with dose escalation up to 90 mg/m2 and dexamethasone 20 mg orally or intravenously on 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day cycle. Study treatment will be given until 8 cycles of treatment are completed or until disease progression, whichever comes first. CFZ with bendamustine and dexamethasone Dexamethasone Subjects will receive Carfilzomib on Days 1, 2, 8, 9, 15, and 16 every 28 days with dose escalation from 27, 36, 45 to 56 mg/ m2 . No matter what target dose the subject will receive, days 1 and 2 doses in the first cycle will always be 20 mg/m2, followed by target dose for all subsequent dates and cycles. Bendamustine will be given IV on days 1 and 2 with dose escalation up to 90 mg/m2 and dexamethasone 20 mg orally or intravenously on 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day cycle. Study treatment will be given until 8 cycles of treatment are completed or until disease progression, whichever comes first.
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) of Carfilzomib in Combination With Bendamustine and Dexamethasone 6 months MTD defined as the highest dose at which ≤20% of participants experience dose-limiting toxicity (DLT), to define the recommended phase II dose. DLT were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute version 4.0. An AE was considered a DLT if it occurred in cycle 1, was deemed related to study treatment, and was one of peripheral neuropathy ≥grade 2, any non-hematologic AE ≥ grade 3, neutropenia grade 4 lasting ≥7 days or with fever, thrombocytopenia grade 4 lasting ≥7 days or with bleeding, or any AE requiring a dose reduction during cycle 1 or a delay in the start of cycle 2.
- Secondary Outcome Measures
Name Time Method Overall Response Rate (ORR) 2 years ORR defined as the number of participants demonstrating complete response or partial response. Complete response defined as complete disappearance of an M-protein and no evidence of MM in the bone marrow. Partial response defined as ≥50% reduction in the level of the serum monoclonal paraprotein, reduction in 24-hour M-protein either by greater than or equal to 90% or to \<200 mg, ≥50% reduction in size of soft tissue plasmacytoma (by radiography or clinical examination), no increase in the number or size of lytic bone lesions.
Time to Next Treatment (TTNT) Up to 6.5 years The TTNT is measured from the date of initiation of treatment to the start date of the next treatment regimen.
Progression Free Survival (PFS) Up to 6.5 Years PFS is defined as the duration of time from start of study treatment to time of progression or death, whichever occurs first.
Time to Best Response 2 years Time to the best response recorded.
Overall Survival (OS) Rate Up to 6.5 Years The percentage of people who are still alive.
Number of Adverse Events (AEs) 30 Days Post Last Dose, Up to approximately 9 months Total number of AEs observed.
Trial Locations
- Locations (1)
Columbia University Irving Medical Center
🇺🇸New York, New York, United States