Safety, Efficacy, and Pharmacodynamics of a 60-Minute Infusion of Carfilzomib for Progressive Multiple Myeloma

NCT01792102 | Unknown Phase 1

• 1 other identifier: IST-CAR-585
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase 1/2, multicenter, open label, dose-escalation, nonrandomized study to evaluate the safety, pharmacodynamics, and efficacy of a 60-minute infusion of carfilzomib for patients with progressive multiple myeloma.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Carfilzomib; Krypolis; 60 minute infusion

Outcome Measures

Primary Outcomes (1)

• Establish maximum tolerated dose (MTD)

  Maximum tolerated dose will be established by the number of dose limiting toxicities and the overall safety and tolerability of the study drug. Safety and tolerability will be determined by the following: 1. incidence and frequency of adverse events throughout the study 2. clinical laboratory test results at study visits 3. vital signs measurements at each study visits 4. medical history and physical examination findings 5. ECOG performance status at study visits 6. concomitant medication usage throughout the study

  monthly, up to 24 months

Secondary Outcomes (1)

• Establish efficacy as assessed by the overall response rate

  monthly, up to 24 months

Other Outcomes (1)

• Relationship of 60-minute infusion of carflizomib with pharmacodynamic markers

  weekly for 2 months

Study Arms (1)

Carfilzomib and Dexamethasone

EXPERIMENTAL

Phase 1: Carfilzomib will be administered at an escalating dose with dexamethasone administered at 8mg. Phase 2: Carfilzomib will be administered at the MTD determined in phase 1. Maintenance: Carfilzomib and dexamethasone will be administered in the same fashion as the previous treatment cycles, but only on days 1, 2, 15, and 16.

Drug: Carfilzomib and Dexamethasone

Interventions

Carfilzomib and Dexamethasone DRUG

Phase 1: Carfilzomib will be administered at an escalating dose by cohort as 60-minute IV infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. On Cycle 1 Days 1 and 2, carfilzomib will be given at 20 mg/m\^2. For all subsequent doses, carfilzomib will be administered at the dose assigned to the cohort (56, 70, or 88 mg/m\^2). Dexamethasone (8 mg IV or PO) will be administered prior to carfilzomib on Days 1, 2, 8, 9, 15, and 16. Phase 2: Carfilzomib will be administered at the MTD determined in phase 1. Maintenance: From Cycle 9 onward, carfilzomib and dexamethasone will be administered in the same fashion as during the previous treatment cycle, but only on days 1, 2, 15, and 16.

Also known as: Krypolis®

Carfilzomib and Dexamethasone

Eligibility Criteria

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

You may qualify if:

• MM with relapsing or progressive disease at study entry
• a. Defined as progressive MM on patient's last treatment regimen
• Measurable disease, as defined by one or more of the following (assessed within 14 days prior to first dose):
• Serum M-protein ≥ 0.5 g/dL, or
• Urine M-protein ≥ 200 mg/24 hours, or
• Only in patients who do not meet a or b, then use serum free light chain (SFLC) \> 100 mg/L (involved light chain) and an abnormal kappa/lamda ratio
• Age ≥ 18 years
• Life expectancy ≥ 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Adequate hepatic function within 14 days prior to first dose, with bilirubin \< 1.5 × the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 × ULN
• LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available.
• Absolute neutrophil count (ANC) ≥ 1000/mm3 within 14 days prior to first dose. Screening ANC is to be independent of granulocyte colony stimulating factor support for ≥ 1 week and pegylated granulocyte colony stimulating factor for ≥ 2 weeks.
• Hemoglobin ≥ 8.0 g/dL within 14 days prior to enrollment. Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed.
• Platelet count ≥ 75,000/mm3 (≥ 50,000/mm\^3 if myeloma involvement in the bone marrow is \> 50%) within 14 days prior to first dose. Patients must not have received platelet transfusions for at least 7 days prior to obtaining the screening platelet count
• Calculated or measured creatinine clearance (CrCl) of ≥ 15 mL/min within 14 days prior to first dose. Calculation are based on a standard formula, such as the Cockcroft and Gault: \[(140 - Age) x Mass (kg) / (72 x Creatinine mg/dL)\]; multiply result by 0.85 if female

You may not qualify if:

• Multiple myeloma of IgM subtype
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Plasma cell leukemia (\> 2.0 × 109/L circulating plasma cells by standard differential)
• Waldenström's macroglobulinemia
• Amyloidosis
• Glucocorticoid therapy (prednisone \> 30 mg/day or equivalent) within 7 days prior to first dose
• Cytotoxic chemotherapy with approved or investigational anticancer therapeutics within 28 days prior to first dose
• Treatment with bortezomib, thalidomide or lenalidomide within 21 days prior to first dose
• Focal radiation therapy within 7 days prior to first dose. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to enrollment (i.e., prior radiation must have been to \< 30% of the bone marrow)
• Immunotherapy within 21 days prior to first dose
• Major surgery within 21 days prior to first dose
• Active congestive heart failure (New York Heart Association \[NYHA\] Classes III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 6 months prior to first dose.
• Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at HBV), or antifungal agents within 14 days prior to first dose
• Known human immunodeficiency virus (HIV) seropositivity
• Known hepatitis B or C virus infection (except for patients with HBV receiving and responding to HBV antiviral therapy: these patients are allowed)

Sponsors & Collaborators

• Oncotherapeutics: lead
• Amgen: collaborator

Study Sites (2)

James R. Berenson M.D. Inc.

West Hollywood, California, 90069, United States

Location

John Theuer Cancer Center Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; 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)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• James Berenson, M.D.

  James Berenson Inc.

  PRINCIPAL INVESTIGATOR

• Joshua Richter, M.D

  John Theurer Cancer Center at Hackensack University Medical Center

  PRINCIPAL INVESTIGATOR

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: January 3, 2013
• First Posted: February 15, 2013
• Study Start: April 1, 2013
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: March 5, 2018

Record last verified: 2018-03

Locations

US (2)