A Study of Carfilzomib vs Best Supportive Care in Subjects With Relapsed and Refractory Multiple Myeloma

NCT01302392 | Completed Phase 3 Results DMC

• 1 other identifier: PX-171-011
• Study Type: interventional
• Target: 315
• Locations: 17 countries
• Sites: 63

Brief Summary

This is a Phase 3, randomized, open-label, multicenter study comparing two treatment regimens for subjects with multiple myeloma who have received all available approved treatment options and may therefore be considered candidates for palliative care.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Time elapsed between the randomization date and the date of death. Participants who were still alive were censored at date when the subject is last known alive or the data cutoff date, whichever occurs earlier.

  From randomization through the final analysis data cutoff with longest follow-up time of approximately 45 months. Median follow up times were 27.8 months and 29.8 months for Carfilzomib and Best Supportive Care groups, respectively.

Secondary Outcomes (7)

• Progression-free Survival

  From randomization through the final analysis data cutoff with longest follow-up time of approximately 31 months. Median follow up times were 26.6 months and 23.1 months for Carfilzomib and Best Supportive Care groups, respectively.

• Overall Response

  From randomization through the final analysis data cutoff with longest follow-up time of approximately 31 months. Median follow up times were 26.6 months and 23.1 months for Carfilzomib and Best Supportive Care groups, respectively.

• Duration of Response

  From the time achieving response through the final analysis data cutoff with longest follow-up time of approximately 29 months.

• Clinical Benefit Response

  From randomization through the final analysis data cutoff with longest follow-up time of approximately 31 months. Median follow up times were 26.6 months and 23.1 months for Carfilzomib and Best Supportive Care groups, respectively.

• Duration of Clinical Benefit

  From time of achieving clinical benefit through the final analysis data cutoff with longest follow-up time of approximately 30 months.

Study Arms (2)

Best Supportive Care

ACTIVE COMPARATOR

Drug: Best Supportive Care

Carfilzomib

EXPERIMENTAL

Drug: Carfilzomib

Interventions

Carfilzomib DRUG

20mg/m² IV on Days 1 and 2 of Cycle 1, escalating to 27 mg/m² IV on Days 8,9,15,and 16 of Cycle 1 and continuing on Days 1,2,8,9,15,and 16 of Cycles 2 through Cycle 9. Cycles 10 and beyond will receive 27 mg/m² IV on Days 1,2,15, and 16 (alternatively, the investigator could choose to continue the dosing frequency on the original dosing days \[Days 1, 2, 8, 9, 15, 16\] for individual subjects).

Also known as: PR-171

Carfilzomib

Best Supportive Care DRUG

Corticosteroid (either prednisolone 30 mg orally (PO) every other day, dexamethasone 6 mg PO every other day, or other equivalent corticosteroid). Optional cyclophosphamide 50 mg PO once daily may be given at the Investigator's discretion (maximum of 1400 mg per 28-day cycle).

Best Supportive Care

Eligibility Criteria

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

You may qualify if:

• Multiple myeloma
• Measurable disease based on central laboratory values, as defined by one or both of the following criteria (assessed within 21 days prior to randomization):
• Serum M-protein
• Serum protein electrophoresis (SPEP): ≥ 0.5 g/dL
• For immunoglobulin A (IgA) patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA): \> 750 mg/dL (0.75 g/dL)
• Urine Bence Jones protein: ≥ 200 mg/24 h
• Responsive (defined as a 25% or greater decrease in M-protein or total protein) to at least one line of prior therapy
• Relapsed multiple myeloma, defined as disease progression while on or after at least 1 prior treatment regimen
• Refractory multiple myeloma, defined as meeting one or more of the following:
• Nonresponsive to most recent therapy (eg, stable disease only, or progressive disease while on treatment)
• Disease progression within 60 days of discontinuation from most recent therapy
• Received 3 or more prior therapeutic regimens for multiple myeloma
• Adequate prior treatment with bortezomib (if less than 4 complete cycles, the reason for discontinuation must be reviewed by the Medical Monitor and the reason documented)
• Prior treatment with an immunomodulatory agent (lenalidomide, if available, and/or thalidomide)
• Prior treatment with an alkylating agent (standard or high-dose)

You may not qualify if:

• Waldenström's macroglobulinemia or IgM myeloma
• Refractory to all prior therapies
• Disease measurable only by serum free light chain assay (SFLC)
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Plasma cell leukemia (\> 2.0 × 10\^9/L circulating plasma cells by standard differential)
• Prior carfilzomib treatment
• Chemotherapy (approved or investigational) within 14 days prior to randomization
• Immunotherapy or antibody therapy within 28 days prior to randomization
• Corticosteroid therapy at a dose equivalent to dexamethasone \> 4 mg/day within 14 days prior to randomization
• Radiotherapy within 7 days prior to randomization
• Major surgery within 21 days prior to randomization
• Congestive heart failure (NYHA Class III or IV) or symptomatic cardiac ischemia, conduction system abnormalities uncontrolled by conventional intervention (conduction abnormalities not clinically warranting intervention are allowed)
• Myocardial infarction in the previous 3 months
• Acute active infection requiring systemic treatment (antibiotics, antivirals, or antifungals) within 14 days prior to randomization
• Known human immunodeficiency virus seropositivity

Sponsors & Collaborators

• Amgen: lead

Study Sites (68)

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Nedlands, Australia

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Perth, Australia

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Linz, Austria

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Salzburg, Austria

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Vienna, Austria

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Arlon, Belgium

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Bruges, Belgium

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Brussels, Belgium

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Roeselare, Belgium

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Brno, Czechia

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Hradec Kralov, Czechia

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Olomouc, Czechia

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Prague, Czechia

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Lyon, France

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Nantes, France

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Nîmes, France

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Dresden, Germany

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Giessen, Germany

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Koblenz, Germany

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Mainz, Germany

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München, Germany

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Ulm, Germany

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Athens, Greece

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Rio Patras, Greece

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Budapest, Hungary

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Debrecen, Hungary

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Győr, Hungary

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Gyula, Hungary

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Kaposvár, Hungary

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Pécs, Hungary

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Szeged, Hungary

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Haifa, Israel

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Jerusalem, Israel

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Kfar Saba, Israel

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Nahariva, Israel

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Petah Tikva, Israel

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Sheba, Israel

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Ancona, Italy

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Novara, Italy

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Roma, Italy

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Torino, Italy

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North Shore, New Zealand

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Gdansk, Poland

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Lodz, Poland

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Piła, Poland

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Torum, Poland

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Warsaw, Poland

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Wroclaw, Poland

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Zamość, Poland

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Moscow, Russia

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Saint Petersburg, Russia

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Belgrade, Serbia

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Niš, Serbia

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Bratislava, Slovakia

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Incheon, South Korea

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Seoul, South Korea

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Barcelona, Spain

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Guipuzcoa, Spain

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Murcia, Spain

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Salamanca, Spain

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Seville, Spain

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Valencia, Spain

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Zaragoza, Spain

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Uppsala, Sweden

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Hampshire, United Kingdom

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London, United Kingdom

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Manchester, United Kingdom

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Oxford, United Kingdom

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Related Publications (2)

• Hajek R, Masszi T, Petrucci MT, Palumbo A, Rosinol L, Nagler A, Yong KL, Oriol A, Minarik J, Pour L, Dimopoulos MA, Maisnar V, Rossi D, Kasparu H, Van Droogenbroeck J, Yehuda DB, Hardan I, Jenner M, Calbecka M, David M, de la Rubia J, Drach J, Gasztonyi Z, Gornik S, Leleu X, Munder M, Offidani M, Zojer N, Rajangam K, Chang YL, San-Miguel JF, Ludwig H. A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS). Leukemia. 2017 Jan;31(1):107-114. doi: 10.1038/leu.2016.176. Epub 2016 Jun 24.

  PMID: 27416912 DERIVED

• Hajek R, Bryce R, Ro S, Klencke B, Ludwig H. Design and rationale of FOCUS (PX-171-011): a randomized, open-label, phase 3 study of carfilzomib versus best supportive care regimen in patients with relapsed and refractory multiple myeloma (R/R MM). BMC Cancer. 2012 Sep 19;12:415. doi: 10.1186/1471-2407-12-415.

  PMID: 22992303 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib

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

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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2011
• First Posted: February 24, 2011
• Study Start: September 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: September 1, 2015
• Last Updated: May 2, 2017
• Results First Posted: August 4, 2015

Record last verified: 2017-04

Locations

IL (6); FR (3); GB (4); PL (7); ES (7); KR (2); SE (1); SL (1); RU (2); DE (6); CZ (4); NZ (1); AU (2); GR (2); IT (4); BE (4); HU (7)