Multiple Myeloma
Conditions
Keywords
PR-171 (CARFILZOMIB), Chemotherapy, 10-228
Brief summary
The purpose of this study is to test a new drug called carfilzomib. It is a type of drug called a proteasome inhibitor. Proteasome breaks down proteins that are no longer useful to the cell. When the proteasome is turned off by a drug (like carfilzomib), useless proteins cannot be broken down. Instead the proteins build up and cause the cell to die. Myeloma cells make a lot of protein and are especially in need of a functional proteasome to survive. Carfilzomib is not approved for use by the Food and Drug Administration to treat myeloma. It is considered an experimental drug. Previous studies have shown that carfilzomib is safe to use. This study will look at what the effects, good and/or bad, carfilzomib has on myeloma.
Interventions
DRUGCarfilzomib
Following enrollment patients will be treated with single agent infusional carfilzomib at 56mg/m2. Carfilzomib will be administered intravenously over 30 minutes on Days 1, 2, 8, 9, 15 and 16 of a 28-day cycle. Dexamethasone 8 mg PO/IV will be administered prior to all carfilzomib doses during the first cycle.
Sponsors
Amgen
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must meet all of the following inclusion criteria to be eligible to enroll in this study. * Patients meeting the criteria for symptomatic multiple myeloma that has relapsed or is refractory to at least 2 prior lines of therapy. * Previous therapy with bortezomib. * Previous therapy with thalidomide or lenalidomide. * Patients must have measurable disease and therefore must have at least one of the following: Serum M-protein ≥1 gm/dL (≥10 gm/L) Urine M-protein ≥200 mg/24 hr Serum FLC assay: involved FLC ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal. * Age ≥ 18 years * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Adequate hepatic function, with serum ALT ≤ 3.5 times the upper limit of normal and serum direct bilirubin ≤ 2 mg/dL (34 µmol/L) within 14 days prior to enrollment * Absolute neutrophil count (ANC) ≥ 1.0 × 109/L within 14 days prior to enrollment Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior to enrollment (participants may be receiving red blood cell \[RBC\] transfusions in accordance with institutional guidelines) * Platelet count ≥ 50 × 109/L (≥ 30 × 109/L if thought to be secondary to myeloma involvement of the bone marrow ) within 14 days prior to enrollment (platelet transfusions are allowed) * Creatinine clearance (CrCl) ≥ 15 mL/minute within 14 days prior to enrollment, either estimated or calculated using a standard formula (eg, Cockcroft and Gault) * Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception. * Male participants must agree to practice contraception.
Exclusion criteria
* Prior treatment with carfilzomib. * Known CNS involvement with myeloma * Pregnant or lactating females * Major surgery within 21 days prior to registration. * Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 7 days prior to enrollment * Known human immunodeficiency virus infection * Active hepatitis B or C infection * Unstable angina or myocardial infarction within 4 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless participant has a pacemaker * Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment. * Concurrent malignancies, except for treated non-melanoma skin cancer and cervical carcinoma in situ. * Significant neuropathy (Grades 3-4, ) within 14 days prior to enrollment * Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib) * Contraindication to any of the required concomitant drugs or supportive treatments, including options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment * Concurrent therapy with any other anticancer therapeutic with activity against multiple myeloma * Concurrent therapy with investigative agents (e.g., antibiotics or antiemetics)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Best Overall Response Rate (ORR) | 2 years | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (POD); POD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Carfilzomib A single arm, open-label, single institution phase 2 clinical trial is planned.
Carfilzomib: Following enrollment patients will be treated with single agent infusional carfilzomib at 56mg/m2. Carfilzomib will be administered intravenously over 30 minutes on Days 1, 2, 8, 9, 15 and 16 of a 28-day cycle. Dexamethasone 8 mg PO/IV will be administered prior to all carfilzomib doses during the first cycle. | 44 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Death | 2 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Carfilzomib |
|---|---|
| Age, Continuous | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Region of Enrollment United States | 44 participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 44 / 44 |
| serious Total, serious adverse events | 28 / 44 |
Outcome results
Primary
To Evaluate the Best Overall Response Rate (ORR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (POD); POD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions
Time frame: 2 years
Population: Participants who completed 4 cycles of treatment or whose disease progressed prior to completion of 4 cycles.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Carfilzomib | To Evaluate the Best Overall Response Rate (ORR) | Complete Response/CR | 1 Participants |
| Carfilzomib | To Evaluate the Best Overall Response Rate (ORR) | Very Good Partial Response/PR | 8 Participants |
| Carfilzomib | To Evaluate the Best Overall Response Rate (ORR) | Partial Response/PR | 9 Participants |
| Carfilzomib | To Evaluate the Best Overall Response Rate (ORR) | Minimal Response/MR | 3 Participants |
| Carfilzomib | To Evaluate the Best Overall Response Rate (ORR) | Stable Disease/SD | 2 Participants |
| Carfilzomib | To Evaluate the Best Overall Response Rate (ORR) | Progressin of Disease/POD | 12 Participants |