Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Cyclophosphamide

Dexamethasone

Dexamethasone acetate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

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.

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.

Carfilzomib

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

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

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.

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

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

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.

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.

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.

Amgen

Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Participants received 36 mg/m² carfilzomib 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), cyclophosphamide administered orally at 300 mg/m² on days 1, 8, and 15, and 40 mg dexamethasone on days 1, 8, 15, and 22, for up to eight 28 day cycles, or until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.

Carfilzomib 36 mg/m²

Participants received 45 mg/m² carfilzomib 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), cyclophosphamide administered orally at 300 mg/m² on days 1, 8, and 15, and 40 mg dexamethasone on days 1, 8, 15, and 22, for up to eight 28 day cycles, or until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.

Carfilzomib 45 mg/m²

Participants received 56 mg/m² carfilzomib 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), cyclophosphamide administered orally at 300 mg/m² on days 1, 8, and 15, and 40 mg dexamethasone on days 1, 8, 15, and 22, for up to eight 28 day cycles, or until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.

Carfilzomib 56 mg/m²

Total

Age, Continuous

Sex: Female, Male

Asian

Black or African American

White

Other

Race

0 (Fully active)

1 (Restrictive but ambulatory)

2 (Ambulatory but unable to work)

Eastern Cooperative Oncology Group (ECOG) Performance Status is used by doctors and researchers to assess how a participants disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. 0 = Fully Active; 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, no self-care, confined to bed or chair; 5 = Dead.

European Cooperative Oncology Group (ECOG) Performance Status

Study Director

The Safety population is defined as all enrolled participants who received any study treatment.

Spots Global Cancer Trial Database for A Multicenter, Open-label, Phase 1b Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma Subjects

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial