A Safety Study of Carfilzomib, Cyclophosphamide & Dexamethasone Prior to ASCT in Patients With Newly Diagnosed Myeloma

Multiple Myeloma Clinical Trial

— 11-MM-01  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01660750
• Other study ID #: AMyC 11-MM-01
• Secondary ID: CAR-IST-520
• Status: Completed
• Phase: Phase 1
• First received: August 7, 2012
• Last updated: October 16, 2017
• Start date: January 2013
• Est. completion date: December 2015

Study information

• Verified date: October 2017
• Source: Criterium, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: December 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Carfilzomib
IV over 30 minutes on Days 1,2,8,9,15, and 16 every 28 days
• Cyclophosphamide
PO on days 1, 8, and 15 every 28 days
• Dexamethasone
40 mg weekly PO or IV on Days 1, 8, 15, and 22, every 28 days.

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina
United States	Samuel Oschin Comprehensive Cancer Center at Cedars-Sinai Medical Center	Los Angeles	California
United States	Comprehensive Cancer Center at Desert Regional Medical Center	Palm Springs	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	University of Massachusettes Memorial	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Criterium, Inc.	Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events as a measure of safety and tolerability	Review of adverse events for safety and to determine the maximum tolerated dose of the combination treatment.	Throughout treatment, estimated to be 4-6 months per patients
Secondary	Overall Response after induction therapy	Overall response (PR, VGPR, CR, sCR)	Every 28 days during induction therapy, estimated to be 4-6 months
Secondary	Overall Response post ASCT	Overall Response (PR, VGPR, CR, sCR) at 3 and 6 months post ASCT.	3 and 6 months post ASCT
Secondary	Time to Progression	Time to progression will be noted if it occurs within 6 months post ASCT.	Througout treatment and 3 and 6 months post ASCT
Secondary	Progression Free Survival		up to 6 months post ASCT
Secondary	Time to Next Therapy	Time to Next Therapy if occurs within 6 months post ASCT	up to 6 months post ASCT