A Multicenter, Open-label, Phase 1b Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma Subjects

Multiple Myeloma Clinical Trial

— CHAMPION 2  

Official title:

A Multicenter, Open-label, Phase 1b Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01980589
• Other study ID #: 2012-003
• Status: Completed
• Phase: Phase 1
• First received: October 28, 2013
• Last updated: May 17, 2016
• Start date: August 2013
• Est. completion date: April 2016

Study information

• Verified date: May 2016
• Source: Onyx Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1b, multicenter, open-label dose-escalation study of twice-weekly carfilzomib in combination with cyclophosphamide and dexamethasone (CCd) as initial therapy for subjects with newly diagnosed multiple myeloma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: April 2016
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 ( ?/?) 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 × 10E9/L

8. Platelet count = 50 × 10E9/L

9. Calculated or measured creatinine clearance (CrCl) of = 15 mL/min

Exclusion Criteria:

1. Planned autologous 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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Carfilzomib
Carfilzomib will be administered as a 30-minute intravenous (IV) infusion on Days 1, 2, 8, 9, 15, and 16. On Days 1 and 2 of Cycle 1, all subjects will receive carfilzomib at 20 mg/m2.
• Cyclophosphamide
Cyclophosphamide will be administered orally (PO) at the dose of 300 mg/m2 on Days 1, 8, and 15.
• Dexamethasone
Dexamethasone will be administered PO or IV at 40 mg on Days 1, 8, 15, and 22.

Locations

Country	Name	City	State
United States	Texas Oncology	Austin	Texas
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	California Cancer Associates for Research and Excellence	Encinitas	California
United States	Horizon Oncology Research	Lafayette	Indiana
United States	Tennessee Oncology	Nashville	Tennessee
United States	Clinical Research Alliance	New York	New York
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	James R. Berenson, MD	West Hollywood	California
United States	The Oncology Institute of Hope and Innovation	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Onyx Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD)	Determine the maximum tolerated dose (MTD) of carfilzomib given twice weekly in combination with cyclophosphamide and dexamethasone (CCd) for subjects with newly diagnosed multiple myeloma. The MTD is defined as the highest carfilzomib dose at which fewer than 33% of subjects experience a treatment-related dose-limiting toxicity (DLT) during the first 28-day cycle.	First cycle treatment over 28-days	Yes
Secondary	Overall Response Rate (ORR)	To estimate overall response rate (ORR) during CCd therapy. ORR is defined as the proportion of subjects with the best overall response of PR or better.	10 months	No
Secondary	Time To Response (TTR)	To estimate time to response (TTR). TTR is defined as the time from the first dose of study treatment until the first evidence of a confirmed response of PR or better.	Up to 10 months	No
Secondary	Safety and Tolerability	Safety and tolerability assessments will include extent of exposure to study treatment, AEs (including SAEs), laboratory values, vital sign results, and ECGs.	Up to 10 months	Yes