Phase 2 Study of Carfilzomib in Relapsed Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )
ClinicalTrials.gov Identifier:
NCT00530816
First received: September 14, 2007
Last updated: August 21, 2012
Last verified: August 2012
  Purpose

Approximately 155 evaluable subjects with relapsed multiple myeloma will be enrolled to evaluate the best overall response rate, safety and tolerability of carfilzomib in this phase 2 study. Patients must have previously received one to three prior therapies and were relapsed to the most recently received therapy.


Condition Intervention Phase
Multiple Myeloma
Drug: carfilzomib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Single-Arm, Phase 2 Study of Carfilzomib in Patients With Relapsed Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Onyx Pharmaceuticals:

Primary Outcome Measures:
  • Best Overall Response Rate [ Time Frame: 2 to 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and Tolerability, Clinical Benefit Response, Time to Progression, Duration of Response, Progression Free Survival, best Overall Response Rate throughout the study, and Overall Survival [ Time Frame: 2 to 12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 155
Study Start Date: September 2007
Estimated Study Completion Date: November 2013
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: carfilzomib
In Cycle 1, subjects will receive carfilzomib 20 mg/m2 IV on Days 1, 2, 8, 9, 15, and 16. If all doses are administered and well-tolerated over the 28-day cycle beginning with Cycle 2 the dose will escalate to 27 mg/m2 IV on Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles.
Drug: carfilzomib
IV push twice weekly for three weeks followed by 12 days of rest. 28 days = 1 cycle. A maximum of 12 cycles will be administered.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Disease Related

  • Multiple myeloma
  • Subjects must have measurable disease, defined as one or more of the following:

    • Serum M-protein ≥ 1 g/dL
    • Urine M-protein ≥ 200 mg/24 hours
  • Subjects must have been responsive (i.e., achieve an MR or better) to standard, first line therapy
  • Relapsed and/or refractory or progressive disease after at least one, but no more than three, prior therapeutic treatments or regimens for multiple myeloma. Refractory disease is defined as ≤ 25% response or progression during therapy or within 60 days after completion of therapy. Induction therapy and stem cell transplant will be considered as one regimen

Demographic

  • Males and females ≥18 years of age
  • Life expectancy of more than three months
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

Laboratory

  • Adequate hepatic function, with bilirubin < 2.0 times the upper limit of normal, and AST and ALT of < 3.0 times the upper limit of normal
  • Uric acid, if elevated, must be corrected to within laboratory normal range prior to dosing
  • Total WBC count ≥ 2,000/mm3, absolute neutrophil count > 1,000/mm3, hemoglobin ≥ 8.0 g/dL, and platelet count > 50,000/mm3
  • Subjects should be platelet transfusion independent
  • Screening ANC should be independent of G-CSF or GM-CSF support for ≥ 1 week and of pegylated G-CSF for ≥ 2 weeks
  • Subjects may receive RBC transfusion or receive supportive care such as erythropoietin and darbepoetin in accordance with institutional guidelines
  • Calculated or measured creatinine clearance of ≥ 30 mL/minute, calculated using the formula of Cockcroft and Gault [(140 - Age) X Mass (kg) / (72 X Creatinine mg/dL)]. Multiply result by 0.85 if female.
  • Serum creatinine ≤ 2 mg/dL

Ethical / Other

  • Written informed consent in accordance with federal, local, and institutional guidelines
  • Female subjects of child-bearing potential must have a negative serum pregnancy test within seven days of the first dose and agree to use dual methods of contraception during and for 3 months following last dose of drug. Post menopausal females (> 45 years old and without menses for > 1 year) and surgically sterilized females are exempt from a pregnancy test. Male subjects must use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with a female of child-bearing potential.
  • Subjects must be able to receive outpatient treatment and laboratory monitoring at the institute that administers agent.

Exclusion Criteria:

Disease Related

  • Multiple Myeloma IgM
  • Subjects previously treated with any proteasome inhibitor (under Amendment 2)
  • Subjects must not be primary refractory to standard first-line therapy
  • Subjects with non-secretory multiple myeloma, defined as < 1 g/dL M-protein in serum, < 200 mg/24 hr M-protein in urine
  • Subjects with disease measurable only by serum free light chain (SFLC) analysis
  • Glucocorticoid therapy (prednisone >10 mg/day orally or equivalent) within the last three weeks
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Plasma cell leukemia
  • Chemotherapy with approved or investigative anticancer therapeutics, including steroid therapy, within the three weeks prior to first dose
  • Radiation therapy or immunotherapy in the previous four weeks; localized radiation therapy within 1 week prior to first dose
  • Participation in an investigational therapeutic study within three weeks or within five drug half-lives (t1/2) prior to first dose, whichever time is greater
  • Prior treatment with carfilzomib

Concurrent Conditions

  • Major surgery within three weeks before Day 1
  • Congestive heart failure (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction in the previous six months
  • Acute active infection requiring systemic antibiotics, antivirals or antifungals within 2 weeks prior to first dose
  • Known or suspected HIV infection or subjects who are HIV seropositive
  • Active hepatitis A, B, or C infection
  • Non-hematologic malignancy within the past three years except a) adequately treated basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, or c) prostate cancer < Gleason Grade 6 with stable PSA
  • Subjects with treatment related myelodysplastic syndrome
  • Significant neuropathy (Grade 3, 4 or Grade 2 with pain) at the time of study initiation
  • Subjects with known contraindication to receiving allopurinol
  • Subjects in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g., due to pre-existing pulmonary, cardiac, or renal impairment
  • Subjects with known or suspected amyloidosis Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis
  • Any clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent

Ethical / Other

  • Female subjects who are pregnant or lactating
  • Serious psychiatric or medical conditions that could interfere with treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00530816

  Show 30 Study Locations
Sponsors and Collaborators
Onyx Therapeutics, Inc.
Investigators
Study Director: Mai Le, MD Onyx Pharmaceuticals
  More Information

No publications provided by Onyx Pharmaceuticals

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )
ClinicalTrials.gov Identifier: NCT00530816     History of Changes
Other Study ID Numbers: PX-171-004
Study First Received: September 14, 2007
Last Updated: August 21, 2012
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 23, 2014