Clinical trial NCT01660750: A Safety Study of Carfilzomib, Cyclophosphamide & Dexamethasone Prior to ASCT in Patients With Newly Diagnosed Myeloma
Official title: A Multi-Center Phase Ib, Open-Label, Dose-Finding Pilot Study to Evaluate the Combination of Carfilzomib and Cyclophosphamide With Dexamethasone Prior to ASCT in Patients With Transplant Eligible Newly Diagnosed Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: newly diagnosed multiple myeloma
transplant eligible multiple myeloma
Lead sponsor: Criterium, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2012-08-09
Enrollment: 29
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: This is a dose finding pilot study to evaluate the safety and determine the maximum tolerated dose of the combination of carfilzomib and cyclophosphamide with dexamethasone (Car-Cy-Dex) prior to autologous stem cell transplant (ASCT) in patients with newly diagnosed transplant eligible multiple myeloma.

Detailed description: This is a dose finding pilot study to evaluate the safety and determine the maximum tolerated dose of the combination of carfilzomib and cyclophosphamide with dexamethasone (Car-Cy-Dex) prior to autologous stem cell transplant (ASCT) in patients with newly diagnosed transplant eligible multiple myeloma. The study will also explore the efficacy of Car-Cy-Dex including overall response after induction therapy, overall response at 3 and 6 months post ASCT, and time to progression, progression free survival, and time to next therapy if it occurs within 6 months post ASCT.

Eligibility criteria: Inclusion Criteria:

* Cytopathologically or histologically confirmed diagnosis of MM
* Measurable disease, as indicated by one or more of the following:
* Serum M-protein ≥ 1.0 g/dL
* Urine Bence Jones protein ≥ 200 mg/24 hr
* Elevated Free Light Chain as per the International Myeloma Working Group (IMWG) criteria
* Males and females ≥ 18 years of age
* Life expectancy of more than 5 months
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
* Adequate hepatic function, with bilirubin \< 2 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3.5 times ULN
* Serum Creatinine Clearance(CrCl) ≥ 30 mL/min, either measured or calculated using a standard formula (e.g. Cockcroft and Gault)
* Additional Laboratory Requirements
* Absolute neutrophil count (ANC) ≥1.0 x 109/L
* Hemoglobin ≥8 g/dL \[transfusion permitted\]
* Platelet count ≥50.0 x 109/L
* Screening ANC should be independent of granulocyte-and granulocyte/macrophage colony stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G-CSF for at least 2 weeks
* Patients may receive RBC or platelet transfusions, if clinically indicated, in accordance with institutional guidelines
* Written informed consent in accordance with federal, local, and institutional guidelines
* Patients must agree to practice contraception
* Male patients must agree not to donate semen or sperm.

Exclusion Criteria:

* Patients with non-secretory or hyposecretory MM
* Prior treatment for MM (prior radiation therapy or dexamethasone up to 160 mg for spinal cord compression is allowed. Other limited field radiation involving ≤ 1/3 of the pelvic area is also allowed)
* Plasma cell leukemia
* Pregnant or lactating females
* Major surgery within 21 days prior to first dose
* Congestive heart failure (CHF) (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction in the previous six months
* Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 14 days prior to first dose
* Patients receiving active treatment or intervention for any other malignancy or patients who, at the Investigator's discretion, may require active treatment or intervention for any other malignancy within 8 months of starting study treatment.
* Serious psychiatric or medical conditions that could interfere with treatment
* Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose and/or within 14 days before study treatment
* Contraindication to any of the required concomitant drugs, including antiviral (e.g. Valacyclovir) and proton-pump inhibitor (e.g. lansoprazole). Corticosteroid therapy in a dose equivalent to dexamethasone ≥ 1.5 mg/day or prednisone ≥ 10 mg/day. (Steroid use is allowed if necessary to treat spinal cord compression and/or hypocalcaemia.)
* Patients in whom the required program of oral and IV fluid hydration is contraindicated, e.g. due to pre-existing pulmonary, cardiac, or renal impairment
* Patients with primary systemic amyloidosis.

Primary outcomes:
measure: Adverse Events as a measure of safety and tolerability
timeFrame: Throughout treatment, estimated to be 4-6 months per patients
Secondary outcomes:
measure: Overall Response after induction therapy
timeFrame: Every 28 days during induction therapy, estimated to be 4-6 months
measure: Overall Response post ASCT
timeFrame: 3 and 6 months post ASCT
measure: Time to Progression
timeFrame: Througout treatment and 3 and 6 months post ASCT
measure: Progression Free Survival
timeFrame: up to 6 months post ASCT
measure: Time to Next Therapy
timeFrame: up to 6 months post ASCT
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Samuel Oschin Comprehensive Cancer Center at Cedars-Sinai Medical Center
state: California
city: Palm Springs
country: United States
facility: Comprehensive Cancer Center at Desert Regional Medical Center
state: California
city: Worcester
country: United States
facility: University of Massachusettes Memorial
state: Massachusetts
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: AMyC
name: Jatin Shah, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AMyC
name: Brian GM Durie, MD
role: PRINCIPAL_INVESTIGATOR
References: