Phase 1b Multicenter Study of Carfilzomib With Lenalidomide and Dexamethasone in Relapsed Multiple Myeloma
This trial is active, not recruiting.
|Condition||relapsed multiple myeloma|
|Treatment||carfilzomib with lenalidomide and dexamethasone|
|Sponsor||Onyx Therapeutics, Inc.|
|Start date||April 2008|
|End date||May 2013|
|Trial size||84 participants|
|Trial identifier||NCT00603447, PX-171-006|
This study will be conducted as an open-label Phase 1b, multicenter study in which subjects will receive carfilzomib, in combination with lenalidomide and dexamethasone, for relapsed multiple myeloma.
|United States||No locations recruiting|
|Other countries||No locations recruiting|
|Long Beach, CA||Pacific Shores Medical Group||no longer recruiting|
|Los Angeles, CA||Cedars Sinai Medical Center||no longer recruiting|
|San Francisco, CA||University of California San Francisco||no longer recruiting|
|Tampa, FL||H. Lee Moffitt Cancer Center & Research Institute||no longer recruiting|
|Chicago, IL||Northwestern University||no longer recruiting|
|Hackensack, NJ||Hackensack University Medical Center||no longer recruiting|
|New York, NY||Cornell University||no longer recruiting|
|Canton, OH||Gabrail Cancer Center||no longer recruiting|
|Houston, TX||MD Anderson Cancer Center||no longer recruiting|
|Seattle, WA||Fred Hutch Cancer Research Center||no longer recruiting|
|Milwaukee, WI||Medical College of Wisconsin||no longer recruiting|
|Montreal, Canada||Jewish General Hospital||no longer recruiting|
|Endpoint classification||safety/efficacy study|
|Intervention model||single group assignment|
To evaluate safety and the maximum tolerated dose (MTD) of carfilzomib with lenalidomide and dexamethasone in relapsed multiple myeloma subjects
time frame: 4 to 18 months
To observe possible early evidence of efficacy and to collect blood for plasma determination of carfilzomib population pharmacokinetic (PK) parameter estimates and variability in these estimates.
time frame: 4 to 18 months
Male or female participants at least 18 years old.
- 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 IgA MM), 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 (see Appendix B) Laboratory
- Adequate hepatic function, with bilirubin < 2 times the upper limit of normal (ULN) and alanine aminotransferase (ALT) < 3 times ULN
- Absolute neutrophil count (ANC) ≥ 1,000/mm3 Hemoglobin ≥ 8 gm/dL Platelet count ≥ 50,000/ mm3 (≥ 30 × 109/L if myeloma involvement in the bone marrow is > 50%)
- Screening ANC should be independent of granulocyte- and granulocyte/macrophage colony stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G CSF for at least 2 weeks.
- Subjects may receive red blood cell (RBC) or platelet transfusions, if clinically indicated, in accordance with institutional guidelines
- Screening platelet count should be independent of platelet transfusions for at least 2 weeks
- Calculated or measured creatinine clearance of ≥ 50 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). Other generally accepted calculation methods can be substituted. Ethical/Other
- Written informed consent in accordance with federal, local, and institutional guidelines
- Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing
- FCBP* must have a negative serum or urine pregnancy test, with a sensitivity of at least 50 mIU/mL within 10-14 days (US/RevAssist®) or 25 mIU/mL within 7-14 days (Canada/RevAidSM), prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or to use two methods of reliable birth control, including at least one highly effective method AND one additional effective method of birth control (contraception) AT THE SAME TIME, beginning 4 weeks prior to initiating treatment with lenalidomide, during therapy, during therapy delay, and continuing for 4 weeks following discontinuation of lenalidomide therapy. If a hormonal method (birth control pills, injections, patch or implants) or IUD is not medically possible for the subject, the subject may use another highly effective method or two barrier methods AT THE SAME TIME. The definition of FCBP for RevAssist and RevAid are summarized in Appendix G.
- Male subjects must agree to NEVER have unprotected sexual contact with a female who can become pregnant and must agree to either completely abstain from sexual contact with females who are pregnant or are able to become pregnant, or he must use a latex condom EVERY TIME he engages in any sexual contact with females who are pregnant or may become pregnant while he is taking lenalidomide and for 4 weeks after he stops taking the drug, even if he has had a successful vasectomy. The subject must agree to inform his physician if he has had unprotected sexual contact with a female who can become pregnant or if he thinks FOR ANY REASON, that his sexual partner may be pregnant.
- Male subjects cannot donate semen or sperm while taking lenalidomide.
- All study participants must be registered into the mandatory RevAssist (US) or RevAid (Canada) programs and be willing and able to comply with the requirements of Rev Assist/RevAid
- Subjects must adhere to the study visit schedule and other protocol requirements and receive outpatient treatment and laboratory monitoring at the institute that administers the drug
- Subjects must agree to take enteric-coated aspirin 81-325 mg orally daily, or if history of prior thrombotic disease or allergy to aspirin, must be fully anticoagulated with warfarin (INR 2-3) or be treated with full-dose, low molecular weight heparin, as if to treat deep venous thrombosis (DVT)/pulmonary embolism.
- 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
- Major surgery within 3 weeks prior to first dose
- 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
- Uncontrolled hypertension
- Acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
- Known or suspected HIV infection, known HIV seropositivity, or 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 prostate specific antigen (PSA) levels
- Serious psychiatric or medical conditions that could interfere with treatment
- Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose and/or within 14 days before enrollment
- Contraindication to any of the required concomitant drugs, including proton-pump inhibitor (e.g., lansoprazole), enteric-coated aspirin or other anticoagulant, or if a history of prior thrombotic disease, warfarin or low molecular weight heparin
- 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
- Prior carfilzomib treatment
|Official title||Phase 1b Multicenter Dose Escalation Study of Carfilzomib With Lenalidomide and Dexamethasone for Safety and Activity in Relapsed Multiple Myeloma|
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