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

NCT ID: NCT01302392

Last Updated: 2017-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 315 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2015-09-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Best Supportive Care

Group Type: ACTIVE_COMPARATOR

Best Supportive Care

Intervention Type: 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).

Carfilzomib

Group Type: EXPERIMENTAL

Carfilzomib

Intervention Type: 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).

Interventions

Carfilzomib

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).

Intervention Type: DRUG

Best Supportive Care

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).

Intervention Type: DRUG

Other Intervention Names

PR-171

Eligibility Criteria

Inclusion Criteria

1. Multiple myeloma

2. 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

3. Responsive (defined as a 25% or greater decrease in M-protein or total protein) to at least one line of prior therapy

4. Relapsed multiple myeloma, defined as disease progression while on or after at least 1 prior treatment regimen

5. 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

6. Received 3 or more prior therapeutic regimens for multiple myeloma

7. 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)

8. Prior treatment with an immunomodulatory agent (lenalidomide, if available, and/or thalidomide)

9. Prior treatment with an alkylating agent (standard or high-dose)

10. Prior treatment with a corticosteroid

11. Criterion no longer applicable (with Amendment 2, Criterion 11, the requirement of "prior treatment with an anthracycline unless not clinically indicated" is removed.)

12. Age ≥ 18 years

13. Life expectancy of at least 1 month

14. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

15. Adequate hepatic function, with serum alanine aminotransferase (ALT) < 4 times the upper limit of normal and serum bilirubin < 2.5 mg/dL (42.5 µmol/L). Patients with total bilirubin ≥ 2.5 mg/dL may enrol if their serum direct bilirubin is < 2.5 mg/dL.

16. Total white blood cell (WBC) count ≥ 1.5 × 10^9/L and absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L (use of colony-stimulating factors to achieve these counts is allowed)

17. Hemoglobin ≥ 7.5 g/dL (75 g/L)

-Use of erythropoietic stimulating factors is allowed:

• For all patients who receive a red blood cell (RBC) transfusion within 28 days of obtaining the Screening hemoglobin value. The following information must be provided for the Medical Monitor's review for assessment for eligibility:

• Pre-transfusion hemoglobin (Hb)
• Number of RBC units administered
• Use of erythropoietic stimulating factors

18. Platelet count ≥ 30 × 10^9/L

-There is no restriction on platelet transfusions or thrombopoietic growth factor before or during the screening period

• For all patients who receive a platelet transfusion within 7 days of obtaining the Screening platelet value, the following information must be provided for the Medical Monitor's review for assessment of eligibility

• Pre-transfusion platelet count
• Number of platelet units administered
• Use of thrombopoietic growth factors

19. Creatinine clearance (CrCl) ≥ 15 mL/minute (either measured or calculated using a standard formula such as Cockcroft and Gault) and dialysis-independent

20. Written informed consent in accordance with regulatory guidelines

21. Female patients of childbearing potential must have a negative serum or urine pregnancy test within 7 days of the first dose of study treatment and agree to use an effective method of contraception during the study and for 3 months following the last dose of study treatment. Post-menopausal females (> 45 years old and without menses for > 1 year) and surgically sterilized females are exempt from these requirements. Male patients must use an effective barrier method of contraception during the study and for 3 months following the last dose if sexually active with a female of childbearing potential.

Exclusion Criteria

1. Waldenström's macroglobulinemia or IgM myeloma

2. Refractory to all prior therapies

3. Disease measurable only by serum free light chain assay (SFLC)

4. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)

5. Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential)

6. Prior carfilzomib treatment

7. Chemotherapy (approved or investigational) within 14 days prior to randomization

8. Immunotherapy or antibody therapy within 28 days prior to randomization

9. Corticosteroid therapy at a dose equivalent to dexamethasone > 4 mg/day within 14 days prior to randomization

10. Radiotherapy within 7 days prior to randomization

11. Major surgery within 21 days prior to randomization

12. 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)

13. Myocardial infarction in the previous 3 months

14. Acute active infection requiring systemic treatment (antibiotics, antivirals, or antifungals) within 14 days prior to randomization

15. Known human immunodeficiency virus seropositivity

16. Active hepatitis A, B, or C infection

17. Other malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix, vulva, or breast; c) prostate cancer of Gleason Score 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder, carcinoma in situ of the breast, or benign tumors of the adrenal or pancreas

18. Significant neuropathy (Grades 3-4, or Grade 2 with pain) at the time of randomization

19. Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a patient's ability to give informed consent

20. Pregnant or lactating females

21. Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity or known history of allergy to carfilzomib, Captisol® (a cyclodextrin derivative used to solubilize carfilzomib) all anticoagulation and antiplatelet options, antiviral drugs; or intolerance to hydration due to preexisting pulmonary or cardiac impairment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Nedlands, , Australia

Perth, , Australia

Linz, , Austria

Salzburg, , Austria

Vienna, , Austria

Arlon, , Belgium

Bruges, , Belgium

Brussels, , Belgium

Roeselare, , Belgium

Brno, , Czechia

Hradec Kralov, , Czechia

Olomouc, , Czechia

Prague, , Czechia

Lyon, , France

Nantes, , France

Nîmes, , France

Dresden, , Germany

Giessen, , Germany

Koblenz, , Germany

Mainz, , Germany

München, , Germany

Ulm, , Germany

Athens, , Greece

Rio Patras, , Greece

Budapest, , Hungary

Debrecen, , Hungary

Győr, , Hungary

Gyula, , Hungary

Kaposvár, , Hungary

Pécs, , Hungary

Szeged, , Hungary

Haifa, , Israel

Jerusalem, , Israel

Kfar Saba, , Israel

Nahariva, , Israel

Petah Tikva, , Israel

Sheba, , Israel

Ancona, , Italy

Novara, , Italy

Roma, , Italy

Torino, , Italy

North Shore, , New Zealand

Gdansk, , Poland

Lodz, , Poland

Piła, , Poland

Torum, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Zamość, , Poland

Moscow, , Russia

Saint Petersburg, , Russia

Belgrade, , Serbia

Niš, , Serbia

Bratislava, , Slovakia

Incheon, , South Korea

Seoul, , South Korea

Barcelona, , Spain

Guipuzcoa, , Spain

Murcia, , Spain

Salamanca, , Spain

Seville, , Spain

Valencia, , Spain

Zaragoza, , Spain

Uppsala, , Sweden

Hampshire, , United Kingdom

London, , United Kingdom

Manchester, , United Kingdom

Oxford, , United Kingdom

Countries

Australia; Austria; Belgium; Czechia; France; Germany; Greece; Hungary; Israel; Italy; New Zealand; Poland; Russia; Serbia; Slovakia; South Korea; Spain; Sweden; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 27416912 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22992303 (View on PubMed)

Other Identifiers

PX-171-011

Identifier Type: -

Identifier Source: org_study_id