Phase 1b Multicenter Study of Carfilzomib With Lenalidomide and Dexamethasone in Relapsed Multiple Myeloma

NCT00603447 | Completed Phase 1 Results

• 1 other identifier: PX-171-006
• Study Type: interventional
• Target: 84
• Locations: 2 countries
• Sites: 12

Brief Summary

To evaluate the safety and maximum tolerated dose (MTD) of carfilzomib in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma

Conditions

Relapsed Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events (AEs)

  Treatment-related are those AEs with possible or probable relationship to carfilzomib, lenalidomide or dexamethasone as assessed by the Investigator. The severity of each adverse event was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0, per the following: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death. Serious adverse events were defined as AEs meeting one of the following: death, life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect in the offspring of an exposed participant, important medical events that may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed above, or pregnancy or suspected pregnancy.

  From the first dose of study drug until 30 days after the last dose; 1 to 52 months, with an average of 12 months.

• Number of Participants With Dose-limiting Toxicities

  Dose-limiting toxicity was defined as any of the following events assessed as related to carfilzomib, lenalidomide, or dexamethasone: Nonhematologic * ≥ Grade 2 neuropathy with pain * ≥ Grade 3 nonhematologic toxicity (excluding nausea, vomiting, diarrhea, hyperglycemia due to dexamethasone, and rash due to lenalidomide) * ≥ Grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal supportive therapy * ≥ Grade 4 fatigue persisting \> 7 days * Treatment delay for toxicity \> 21 days Hematologic * Grade 4 neutropenia (absolute neutrophil count \[ANC\] \< 500/mm³) \> 7 days * Febrile neutropenia (ANC \< 1,000/mm³ with fever ≥ 38.3ºC) * Grade 4 thrombocytopenia (platelets \< 25,000/mm³) for \> 7 days despite holding treatment, or Grade 3 or 4 thrombocytopenia associated with bleeding * Treatment delay for toxicity \> 21 days. The maximum-tolerated dose was defined as the dose level below which a drug-related DLT was observed in ≥ 33% of participants in a cohort.

  Cycle 1, 28 days

Study Arms (1)

Carfilzomib + Lenalidomide + Dexamethasone

EXPERIMENTAL

Treatment during Cycles 1 through 12 consisted of carfilzomib (15, 20, or 20/27 mg/m²) on Days 1, 2, 8, 9, 15, and 16; lenalidomide (10, 15, 20, or 25 mg) on Days 1 to 21; and low-dose dexamethasone (40 mg) given 30 minutes to 4 hours before the carfilzomib dose on Days 1, 8, and 15, as well as on Day 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator's discretion.

Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

Carfilzomib for Injection was administered intravenously over 10 minutes on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for the first 12 cycles. Each dose of Carfilzomib for Injection was normalized to body surface area.

Also known as: Kyprolis®

Carfilzomib + Lenalidomide + Dexamethasone

Lenalidomide DRUG

Lenalidomide was administered orally on Days 1 to 21 of each 28-day cycle.

Also known as: REVLIMID®

Carfilzomib + Lenalidomide + Dexamethasone

Dexamethasone DRUG

Dexamethasone 40 mg orally or intravenous equivalent was administered 30 minutes to 4 hours before carfilzomib on Days 1, 8, and 15, as well as on Day 22 of each 28-day cycle.

Carfilzomib + Lenalidomide + Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Disease related:
• Symptomatic multiple myeloma
• Relapsed or progressive disease after at least one but no more than three prior therapeutic treatments or regimens for multiple myeloma
• Prior therapeutic treatment regimens may have included bortezomib, lenalidomide, and/or thalidomide, among other agents.
• If previously treated with lenalidomide or bortezomib, the subject must not have progressed during the first 3 months of treatment with the drug and must not have discontinued treatment due to lenalidomide intolerance (bortezomib intolerant subjects may enroll).
• Measurable disease, as indicated by one or more of the following:
• Serum M-protein ≥ 0.5 g/dL
• Urine Bence-Jones protein ≥ 200 mg/24 h
• If Serum Protein Electrophoresis is felt to be unreliable for routine M-protein measurement (particularly for patients with Immunoglobulin (Ig)A multiple myeloma), then quantitative immunoglobulin levels can be accepted.
• Prior to enrollment, sites must provide evidence of myeloma progression/relapse, with start and stop dates of the most recent treatment regimen, as well as best tumor response to all prior treatment regimens.
• Demographic
• Males and females ≥ 18 years of age
• Life expectancy of more than three months
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Laboratory

You may not qualify if:

• Disease related
• Subjects with non-secretory or hyposecretory multiple myeloma, defined as \< 0.5 g/dL M-protein in serum, \< 200 mg/24 hr Bence Jones protein in urine, or disease only measured by serum free light chain (FLC)
• Subjects who never achieved at least a durable minimal response (MR, ≥ 25% reduction in M-protein for at least 6 weeks) on any prior therapy
• Corticosteroid therapy in a dose equivalent to dexamethasone ≥ 4 mg/day or prednisone ≥ 20 mg/day within 3 weeks prior to first dose
• Use of any other experimental drug or therapy within 28 days of baseline
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Plasma cell leukemia
• Waldenström's macroglobulinemia
• Chemotherapy with approved or investigative anticancer therapeutics, including steroid therapy dose as defined above, within 3 weeks prior to first dose
• Radiation therapy or immunotherapy within 4 weeks prior to first dose; localized radiation therapy within 1 week prior to first dose
• Planned radiation therapy that occurs after the start of treatment
• Participation in an investigational therapeutic study within 3 weeks or within 5 drug half-lives (t1/2) prior to first dose, whichever time is greater.
• Concurrent conditions
• Pregnant or lactating females
• History of allergy to boron or mannitol

Sponsors & Collaborators

• Amgen: lead

Study Sites (12)

Pacific Shores Medical Group

Long Beach, California, 90813, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Cornell University

New York, New York, 10021, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutch Cancer Research Center

Seattle, Washington, 98103-1204, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (2)

• Wang M, Martin T, Bensinger W, Alsina M, Siegel DS, Kavalerchik E, Huang M, Orlowski RZ, Niesvizky R. Phase 2 dose-expansion study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma. Blood. 2013 Oct 31;122(18):3122-8. doi: 10.1182/blood-2013-07-511170. Epub 2013 Sep 6.

  PMID: 24014245 DERIVED

• Niesvizky R, Martin TG 3rd, Bensinger WI, Alsina M, Siegel DS, Kunkel LA, Wong AF, Lee S, Orlowski RZ, Wang M. Phase Ib dose-escalation study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma. Clin Cancer Res. 2013 Apr 15;19(8):2248-56. doi: 10.1158/1078-0432.CCR-12-3352. Epub 2013 Feb 27.

  PMID: 23447001 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Lenalidomide; 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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; 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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2008
• First Posted: January 29, 2008
• Study Start: May 1, 2008
• Primary Completion: May 1, 2013
• Study Completion: January 1, 2016
• Last Updated: May 30, 2017
• Results First Posted: June 3, 2015

Record last verified: 2017-04

Locations

US (11); CA (1)