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

NCT01980589 | Completed Phase 1 Results

• 1 other identifier: 2012-003
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 9

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.

Conditions

Multiple Myeloma

Keywords

multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose-limiting Toxicities (DLTs)

  The MTD is defined as the highest carfilzomib dose at which fewer than 33% of participants experience a treatment-related dose-limiting toxicity (DLT) during the first 28-day cycle. The number of participants who experienced a DLT is reported. Dose-limiting toxicities are defined as any of the following carfilzomib-related adverse events: Nonhematologic: * ≥ Grade 3 non-hematological toxicity * ≥ Grade 3 acute kidney injury (creatinine \> 3 × baseline or \> 4.0 mg/dL) lasting \> 72 hours Hematologic: * Grade 4 neutropenia (absolute neutrophil count \[ANC\] \< 0.5 × 10\^9/L) lasting for \> 7 days * Febrile neutropenia (ANC \< 1.0 × 10\^9/L with a fever ≥ 38.3ºC) of any duration * Grade 4 thrombocytopenia (\< 25 × 10\^9/L) that persists for \> 14 days, despite holding treatment * Grade 3 or 4 thrombocytopenia associated with \> Grade 1 bleeding

  First cycle treatment over 28-days

Secondary Outcomes (3)

• Overall Response Rate (ORR)

  Disease response was assessed at the end of each cycle and 30 days after the last treatment; maximum treatment duration was 32 weeks.

• Time To Response (TTR)

  Disease response was assessed at the end of each cycle and 30 days after the last treatment; maximum treatment duration was 32 weeks.

• Number of Participants With Adverse Events

  From first dose of study drug until 30 days after last dose; median duration of treatment was 31 weeks.

Study Arms (1)

Carfilzomib, Cyclophosphamide and Dexamethasone (CCd)

EXPERIMENTAL

Participants received carfilzomib, cyclophosphamide and dexamethasone for up to eight 28-day cycles, or until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.

Drug: Carfilzomib; Drug: Cyclophosphamide; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

Carfilzomib administered as a 30-minute intravenous (IV) infusion on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. On Days 1 and 2 of Cycle 1, all participants received carfilzomib at 20 mg/m².

Also known as: PR-171, PR171, Kyprolis® (carfilzomib) for Injection

Carfilzomib, Cyclophosphamide and Dexamethasone (CCd)

Cyclophosphamide DRUG

Cyclophosphamide administered orally (PO) at the dose of 300 mg/m² on Days 1, 8, and 15 of each 28-day cycle.

Carfilzomib, Cyclophosphamide and Dexamethasone (CCd)

Dexamethasone DRUG

Dexamethasone administered PO or IV at 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle.

Carfilzomib, Cyclophosphamide and Dexamethasone (CCd)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed multiple myeloma
• 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
• Males and females ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Adequate hepatic function
• Left ventricular ejection fraction (LVEF) ≥ 40%
• Absolute neutrophil count (ANC) ≥ 1.0 × 10\^9/L
• Platelet count ≥ 50 × 10\^9/L
• Calculated or measured creatinine clearance (CrCl) of ≥ 15 mL/min

You may not qualify if:

• Planned autologous hematopoietic stem cell transplantation (HSCT) for the initial therapy of newly diagnosed multiple myeloma
• Multiple myeloma of immunoglobulin M (IgM) subtype
• Prior systemic treatment for multiple myeloma
• Glucocorticoid therapy within 14 days prior to enrollment that equals or exceeds the equivalent of dexamethasone 160 mg
• Known amyloidosis
• 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.
• 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)
• Significant neuropathy (Grades ≥ 2) within 14 days prior to enrollment
• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (9)

California Cancer Associates for Research and Excellence

Encinitas, California, United States

Location

James R. Berenson, MD

West Hollywood, California, United States

Location

The Oncology Institute of Hope and Innovation

Whittier, California, United States

Location

Horizon Oncology Research

Lafayette, Indiana, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States

Location

Clinical Research Alliance

New York, New York, United States

Location

Tennessee Oncology

Nashville, Tennessee, United States

Location

Texas Oncology

Austin, Texas, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; WW Domain-Containing Oxidoreductase; Cyclophosphamide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Short Chain Dehydrogenase-Reductases; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Alcohol Oxidoreductases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; Tumor Suppressor Proteins; Neoplasm Proteins; Proteins; Amino Acids, Peptides, and Proteins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Study Director
• Organization: Amgen, Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2013
• First Posted: November 11, 2013
• Study Start: August 1, 2013
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: May 30, 2017
• Results First Posted: October 31, 2016

Record last verified: 2017-04

Locations

US (9)