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OpenTrials
Completed

NCT Number: NCT01980589

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

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

California Cancer Associates for Research and Excellence, Encinitas, California, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

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.

Other names: PR-171, PR171, Kyprolis® (carfilzomib) for Injection

Cyclophosphamide

Drug

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

Dexamethasone

Drug

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

Primary outcomes

  1. Number of Participants With Dose-limiting Toxicities (DLTs)

    Time frame: First cycle treatment over 28-days

    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

Secondary outcomes

  1. Overall Response Rate (ORR)

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

    Participants were evaluated for disease response and progression by the investigator according to the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC). Disease response and progression assessments included serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), serum immunofixation, serum free light chain (SFLC), bone marrow sample (including fluorescent in situ hybridization [FISH]), plasmacytoma evaluation, and skeletal survey. Overall response rate is defined as the percentage of participants with a best response of stringent complete response, complete response, very good partial response (VGPR), or partial response.

  2. Time To Response (TTR)

    Time frame: 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 is defined as months from treatment start to first documentation of response of partial response or better. Summary of time to response includes confirmed responders of PR or better only.

  3. Number of Participants With Adverse Events

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

    Adverse events (AEs) were graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 and using the following scale:

    Grade 1 = Mild, Grade 3 = Moderate; Grade 3 = Severe, Grade 4 = Life-threatening; Grade 5 = Fatal.

Sponsors and collaborators

Lead sponsor

Amgen

Industry

Registry information

Acronym: CHAMPION 2

Important dates

Study start
2013
Primary completion
2016
Study completion
2016
First posted
Nov 11, 2013
Registry last updated
May 30, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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