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

NCT00150462 | Completed Phase 1 Results

• 1 other identifier: PX-171-002
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Waldenstrom's Macroglobulinemia; Non-Hodgkin's Lymphoma; Hodgkin's Disease; Multiple Myeloma

Keywords

Hematological; Proteasome; Myeloma; Lymphoma

Outcome Measures

Primary Outcomes (5)

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

  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.

  28 days

• Maximum Observed Plasma Concentration of Carfilzomib (Cmax)

  Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.

• Time to Maximum Observed Plasma Concentration of Carfilzomib (Tmax)

  Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.

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

  Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.

• Area Under the Concentration-time Curve Extrapolated to Infinity (AUCinf) for Carfilzomib

  Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.

Secondary Outcomes (4)

• Best Clinical Response to Treatment

  From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.

• Duration of Response

  From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.

• Time to Progression

  From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.

• Progression-free Survival

  From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.

Study Arms (11)

CFZ 1.2 mg/m²

EXPERIMENTAL

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.

Drug: Carfilzomib

CFZ 2.4 mg/m²

EXPERIMENTAL

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.

Drug: Carfilzomib

CFZ 4.0 mg/m²

EXPERIMENTAL

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.

Drug: Carfilzomib

CFZ 6.0 mg/m²

EXPERIMENTAL

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.

Drug: Carfilzomib

CFZ 8.4 mg/m²

EXPERIMENTAL

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.

Drug: Carfilzomib

CFZ 11.0 mg/m²

EXPERIMENTAL

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.

Drug: Carfilzomib

CFZ 15.0 mg/m²

EXPERIMENTAL

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.

Drug: Carfilzomib

CFZ 20.0 mg/m²

EXPERIMENTAL

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.

Drug: Carfilzomib

CFZ 27.0 mg/m²

EXPERIMENTAL

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.

Drug: Carfilzomib

CFZ 20/27 mg/m²

EXPERIMENTAL

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.

Drug: Carfilzomib

CFZ 20/27 mg/m² + DEX

EXPERIMENTAL

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).

Drug: Carfilzomib; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

Administered as an IV bolus dose

Also known as: PR-171, Kyprolis

CFZ 1.2 mg/m²; CFZ 11.0 mg/m²; CFZ 15.0 mg/m²; CFZ 2.4 mg/m²; CFZ 20.0 mg/m²; CFZ 20/27 mg/m²; CFZ 20/27 mg/m² + DEX; CFZ 27.0 mg/m²; CFZ 4.0 mg/m²; CFZ 6.0 mg/m²; CFZ 8.4 mg/m²

Dexamethasone DRUG

Administered orally prior to carfilzomib

CFZ 20/27 mg/m² + DEX

Eligibility Criteria

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

You may qualify if:

• Written informed consent in accordance with federal, local, and institutional guidelines
• Males and females ≥18 years of age
• Histologically confirmed diagnosis of one of the hematologic malignancies below:
• Multiple myeloma (MM)
• Non-Hodgkin's lymphoma (NHL)
• Waldenström's Macroglobulinemia (WM)
• Hodgkin's disease (HD)
• Subjects who are refractory or relapsed following at least two prior therapies
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
• Adequate cardiovascular function without symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction in the previous six months
• Adequate hepatic function, with bilirubin \< 2.0 times the upper limit of normal, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of \< 3.0 times the upper limit of normal
• Total white blood cell (WBC) count ≥ 2,000/mm³, absolute neutrophil count (ANC) ≥ 1000/mm³, hemoglobin ≥ 8.0 g/dL, and platelet count ≥ 50,000/mm³
• Screening ANC should be independent of granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) support for ≥ 1 week and of pegylated G-CSF for ≥ 2 weeks)
• Subjects receiving supportive care including erythropoietin, darbepoetin and/or bisphosphonates can continue to do so, but must be transfusion independent; subjects receiving erythropoietic support must remain on the same dose for the first 28 days of study participation
• An estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of Cockroft and Gault

You may not qualify if:

• Female subjects who are pregnant or lactating
• Subjects who are transfusion dependent
• Subjects with NHL or HL who have received steroid therapy in the previous seven days
• Subjects with MM or Waldenström's Macroglobulinemia who have received steroid therapy in the previous three weeks, except for MM subjects in the Carfilzomib + DEX Expansion Cohort, where previous treatment with dexamethasone will be allowed. The dose and schedule of administration of dexamethasone will be adjusted to that used in the protocol
• Radiation, chemotherapy, or immunotherapy in the previous four weeks, or subjects who, in the judgment of the Investigator, have not recovered from the effects of previous therapy
• For the Dose Escalation period, subjects who have received prior radioimmunotherapy with anti-cluster of differentiation (CD)20 monoclonal antibodies such as Bexxar® or Zevalin®; subjects treated with these products will be allowed in the Dose Expansion period
• Subjects who have received allogeneic stem cell transplant therapy
• Subjects with NHL or HL who have received autologous stem cell transplant therapy and have relapsed within 100 days of therapy
• Rituxan therapy within three months before Day 1 unless there is evidence of disease progression
• Major surgery within three weeks before Day 1
• Congestive heart failure (CHF) (New York Heart Association class III to IV)
• Acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
• Subjects who are known or suspected of having human immunodeficiency virus (HIV) infection or who are HIV seropositive
• Active hepatitis A, B, or C infection; or positive for Hepatitis C ribonucleic acid (RNA) or hepatitis B antigen
• Non-hematologic malignancy within the past three years except a) adequately treated basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, or c) prostate cancer with stable prostate specific antigen (PSA) levels for three years

Sponsors & Collaborators

• Amgen: lead

Study Sites (5)

Tower Cancer Research Foundation

Beverly Hills, California, 90211-1850, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Weil Medical College of Cornell University

New York, New York, 10021, United States

Location

Herbert Irving Comprehensive Cancer Center, Columbia University

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia; Lymphoma, Non-Hodgkin; Hodgkin Disease; Multiple Myeloma; Neoplasms, Plasma Cell; Lymphoma

Interventions

carfilzomib; Dexamethasone

Condition Hierarchy (Ancestors)

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; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2005
• First Posted: September 8, 2005
• Study Start: September 1, 2005
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: May 2, 2017
• Results First Posted: December 3, 2015

Record last verified: 2017-04

Locations

US (5)