Clinical trial NCT01980589: A Multicenter, Open-label, Phase 1b Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma Subjects
Official title: A Multicenter, Open-label, Phase 1b Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: multiple myeloma
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2013-11-11
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective was to determine the maximum tolerated dose of carfilzomib given twice weekly in combination with cyclophosphamide and dexamethasone for patients with newly diagnosed multiple myeloma.


Eligibility criteria: Inclusion Criteria:

1. Newly diagnosed multiple myeloma
2. Measurable disease, as defined by 1 or more of the following

   * Serum M-protein ≥ 0.5 g/dL, or
   * Urine M-protein ≥ 200 mg/24 hours, or
   * In subjects without detectable serum or urine M-protein, serum free light chain (SFLC) \> 100 mg/L (involved light chain) and an abnormal kappa lambda ( κ/λ) ratio
3. Males and females ≥ 18 years of age
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
5. Adequate hepatic function
6. Left ventricular ejection fraction (LVEF) ≥ 40%
7. Absolute neutrophil count (ANC) ≥ 1.0 × 10\^9/L
8. Platelet count ≥ 50 × 10\^9/L
9. Calculated or measured creatinine clearance (CrCl) of ≥ 15 mL/min

Exclusion Criteria:

1. Planned autologous hematopoietic stem cell transplantation (HSCT) for the initial therapy of newly diagnosed multiple myeloma
2. Multiple myeloma of immunoglobulin M (IgM) subtype
3. Prior systemic treatment for multiple myeloma
4. Glucocorticoid therapy within 14 days prior to enrollment that equals or exceeds the equivalent of dexamethasone 160 mg
5. Known amyloidosis
6. Active congestive heart failure (New York Heart Association \[NYHA\] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 6 months prior to enrollment.
7. Known human immunodeficiency virus (HIV) seropositive, hepatitis C infection, and/or hepatitis B (subjects with hepatitis B surface antigen \[SAg\] or core antibody receiving and responding to antiviral therapy directed at hepatitis B are allowed)
8. Significant neuropathy (Grades ≥ 2) within 14 days prior to enrollment
9. 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

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicities (DLTs)
timeFrame: First cycle treatment over 28-days
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Disease response was assessed at the end of each cycle and 30 days after the last treatment; maximum treatment duration was 32 weeks.
measure: Time To Response (TTR)
timeFrame: Disease response was assessed at the end of each cycle and 30 days after the last treatment; maximum treatment duration was 32 weeks.
measure: Number of Participants With Adverse Events
timeFrame: From first dose of study drug until 30 days after last dose; median duration of treatment was 31 weeks.
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: California Cancer Associates for Research and Excellence
state: California
city: West Hollywood
country: United States
facility: James R. Berenson, MD
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Lafayette
country: United States
facility: Horizon Oncology Research
state: Indiana
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: New York
country: United States
facility: Clinical Research Alliance
state: New York
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: