Phase I/II Study of Carfilzomib in Combination With Bendamustine and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma
Overview
- Phase
- Phase 1
- Intervention
- Bendamustine
- Conditions
- Multiple Myeloma
- Sponsor
- Siyang Leng
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Maximum Tolerated Dose (MTD) of Carfilzomib in Combination With Bendamustine and Dexamethasone
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Siyang Leng
Assistant Professor of Medicine
Columbia University
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 18 years.
- •Life expectancy ≥ 3 months.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
CFZ with bendamustine and 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.
Intervention: Bendamustine
CFZ with bendamustine and 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.
Intervention: Carfilzomib
CFZ with bendamustine and 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.
Intervention: Dexamethasone
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD) of Carfilzomib in Combination With Bendamustine and Dexamethasone
Time Frame: 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 Outcomes
- Overall Response Rate (ORR)(2 years)
- Time to Next Treatment (TTNT)(Up to 6.5 years)
- Progression Free Survival (PFS)(Up to 6.5 Years)
- Time to Best Response(2 years)
- Overall Survival (OS) Rate(Up to 6.5 Years)
- Number of Adverse Events (AEs)(30 Days Post Last Dose, Up to approximately 9 months)