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A Randomized, Open-label, Phase 3 Study of Carfilzomib vs Best Supportive Care in Subjects With Relapsed and Refractory Multiple Myeloma

Phase 3
18 Years
Open (Enrolling)
Multiple Myeloma

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Trial Information

A Randomized, Open-label, Phase 3 Study of Carfilzomib vs Best Supportive Care in Subjects With Relapsed and Refractory Multiple Myeloma

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 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

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

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 Criterion no longer applicable (with Amendment 2, Criterion 11, the requirement of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 × 109/L and absolute neutrophil count (ANC)
≥ 1.0 × 109/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 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 Hb

- Number of RBC units administered

- Use of erythropoietic stimulating factors

18. Platelet count ≥ 30 × 109/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 × 109/L circulating plasma cells by standard

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

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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall Survival

Outcome Description:

The primary objective of this study is to compare overall survival (OS) in patients with refractory multiple myeloma relapsed after at least 3 prior regimens who are randomized to receive either carfilzomib (Regimen C) or best supportive care (Regimen BSC).

Outcome Time Frame:

Up to 3 years

Safety Issue:


Principal Investigator

Roman Hajek, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Hospital, Brno, Czech Republic


Austria: Federal Office for Safety in Health Care

Study ID:




Start Date:

September 2010

Completion Date:

January 2015

Related Keywords:

  • Multiple Myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell