Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Lymphoma

Hematologic Neoplasms

Hodgkin Disease

Waldenstrom Macroglobulinemia

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphosarcoma

Hodgkin Lymphoma

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Dexamethasone acetate

Proteasome Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Participants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.

Participants received carfilzomib 2.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.

Participants received carfilzomib 4.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.

Participants received carfilzomib 6.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.

Participants received carfilzomib 8.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.

Participants received carfilzomib 11.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.

Participants received carfilzomib 115.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.

Participants received carfilzomib 20.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.

Participants received carfilzomib 27.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.

Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.

Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles. Participants also received 20 mg dexamethasone (DEX) administered before each dose of carfilzomib (i.e. 40 mg weekly).

Carfilzomib

The purpose of this study is to test the safety and tolerability of carfilzomib at different dose levels on hematological cancers such as multiple myeloma, non-Hodgkin's lymphoma, Hodgkin's disease, or Waldenstrom's macroglobulinemia. Carfilzomib is a proteasome inhibitor, an enzyme responsible for degrading a wide variety of cellular proteins.

Safety Study of the Proteasome Inhibitor PR-171 (Carfilzomib for Injection) in Patients With Hematological Malignancies

A Phase I Study of the Safety and Pharmacokinetics of Escalating Intravenous Doses of the Proteasome Inhibitor PR-171 in Patients With Hematological Malignancies

A DLT was defined as any of the following occurring in the first 28 days of study participation:

Nonhematologic:

* \> Grade 2 neuropathy with pain
* ≥ Grade 3 nonhematologic toxicity (excluding nausea, vomiting, or diarrhea)
* ≥ Grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal antiemetic/antidiarrheal therapy

Hematologic:

* Grade 4 neutropenia (absolute neutrophil count \[ANC\] \< 0.5 × 10ˆ9/L) lasting ≥ 14 days without hematopoietic growth factor support
* Febrile neutropenia (ANC \< 1.0 × 10ˆ9/L with a fever ≥ 38.3°C)
* Grade 4 thrombocytopenia (platelets \< 25.0 × 10ˆ9/L) or thrombocytopenia associated with bleeding.

Toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI) version 3.0.

Disease response criteria for NHL were according to the International Working Group Criteria for Non-Hodgkin's Lymphoma. Disease response criteria for Multiple Myeloma were according to the European Group for Blood and Marrow Transplantation (EBMT). Disease response criteria for WM were according to the consensus panel recommendations from the Second International Workshop on Waldenström's Macroglobulinemia. The disease response criteria for Hodgkin's Lymphoma are defined as follows:

* Complete response: total resolution of measurable disease parameters.
* Partial response: a ≥ 50% resolution without the appearance of new disease.
* Stable disease: between \< 50% resolution and ≤ 25% increases in measurable disease parameters without appearance of new disease.
* Progressive disease: an increase of \> 25% in measurable disease parameters.

Best clinical response is the best response observed from the start of study treatment until disease progression or death.

Duration of objective response is defined as the time from the date of first documented assessment of clinical response (confirmed or unconfirmed complete response, partial response, or minimal response) to the date of documented assessment of progressive disease or death, whichever comes first, plus one day. Participants without tumor progression or death were censored at the date of their last valid clinical response assessment.

Median duration of response was calculated using the Kaplan-Meier method.

Time to progressive disease is defined as the time from the date of Cycle 1, Day 1 of treatment to the date of documented assessment of progressive disease, plus one day. Participants without tumor progression were censored at the date of their last clinical response assessment.

Median time to progression was calculated using the Kaplan-Meier method.

Progression-free survival is defined as the time from the date of Cycle 1, Day 1 of treatment to the date of documented assessment of progressive disease or death, whichever comes first, plus one day. Participants without tumor progression or death were censored at the date of their last valid clinical response assessment. Median progression-free survival was calculated using the Kaplan-Meier method.

Amgen

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

CFZ 1.2 mg/m²

CFZ 2.4 mg/m²

CFZ 4.0 mg/m²

CFZ 6.0 mg/m²

CFZ 8.4 mg/m²

CFZ 11.0 mg/m²

Participants received carfilzomib 15.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.

CFZ 15.0 mg/m²

CFZ 20.0 mg/m²

CFZ 27.0 mg/m²

CFZ 20/27 mg/m²

CFZ 20/27 mg/m² + DEX

Total

Dose Escalation (Part 1)

Dose Expansion (Part 2)

Age, Continuous

Sex: Female, Male

African American

Caucasian

Hispanic

Native American

Race/Ethnicity, Customized

Non-Hodgkin's Lymphoma

Waldenstrom's Macroglobulinemia

Hodgkin's Disease

Disease Diagnosis

Study Director

Safety-evaluable: All participants who were enrolled and received at least 1 dose of carfilzomib

Number of Participants With Dose-limiting Toxicities (DLTs)

Participants in the Dose Expansion phase received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.

CFZ 20/27 mg/m² (±DEX)

Participants with available pharmacokinetic (PK) data. Cmax was only determined for cohorts receiving carfilzomib ≥ 11 mg/m². For cohorts with carfilzomib dose at 1.2-8.4 mg/m², carfilzomib was measurable at too few time points to allow a good estimation. Participants in the two Dose Expansion cohorts (20/27 mg/m²) were combined for PK analyses.

Maximum Observed Plasma Concentration of Carfilzomib (Cmax)

Complete Response

Partial Response

Minimal Response

Stable Disease/No Change

Progressive Disease

Unknown

Biologic response-evaluable: All participants who received at least 1 cycle of carfilzomib and had both baseline and at least 1 post-baseline disease assessment.

Best Clinical Response to Treatment

Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15, and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.

Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15, and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles. Participants also received 20 mg dexamethasone (DEX) administered before each dose of carfilzomib (i.e. 40 mg weekly).

Biologic response-evaluable participants with an objective response

Duration of Response

Time to Progression

Progression-free Survival

Participants with available pharmacokinetic (PK) data. Tmax was only determined for cohorts receiving carfilzomib ≥ 11 mg/m². For cohorts with carfilzomib dose at 1.2-8.4 mg/m², carfilzomib was measurable at too few time points to allow a good estimation. Participants in the two Dose Expansion cohorts (20/27 mg/m²) were combined for PK analyses.

Time to Maximum Observed Plasma Concentration of Carfilzomib (Tmax)

Participants with available pharmacokinetic (PK) data. AUClast was only determined for cohorts receiving carfilzomib ≥ 11 mg/m². For cohorts with carfilzomib dose at 1.2-8.4 mg/m², carfilzomib was measurable at too few time points to allow a good estimation. Participants in the two Dose Expansion cohorts (20/27 mg/m²) were combined for PK analyses.

Area Under the Concentration-time Curve to Last Measureable Timepoint (AUClast) for Carfilzomib

Participants with available pharmacokinetic (PK) data. AUCinf was only determined for cohorts receiving carfilzomib ≥ 11 mg/m². For cohorts with carfilzomib dose at 1.2-8.4 mg/m², carfilzomib was measurable at too few time points to allow a good estimation. Participants in the two Dose Expansion cohorts (20/27 mg/m²) were combined for PK analyses.

Spots Global Cancer Trial Database for Safety Study of the Proteasome Inhibitor PR-171 (Carfilzomib for Injection) in Patients With Hematological Malignancies

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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