|Phase II, Phase I||Biomarker/Laboratory analysis, Treatment||Active||18 and over||Pharmaceutical / Industry||PrE1003|
RV-MM-PrECOG-0394, MAYO-MC0885, MC0885, MAYO-08-003156, CELGENE-RV-MM-PI-0394, NCT00790842
Patients with previously treated multiple myeloma and kidney dysfunction will be treated with lenalidomide and low-dose dexamethasone. Phase I will study the side effects and best dose of lenalidomide when given together with low-dose dexamethasone therapy. After the maximum safe and tolerated dose is found in Phase I, the study will proceed to Phase II. Phase II will study how well the the treatment works in patients with previously treated (relapsed or refractory) multiple myeloma and kidney dysfunction.
Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with dexamethasone may kill more cancer cells. Lenalidomide and dexamethasone may have different effects in patients who have changes in their kidney function.
Further Study Information
Multiple Myeloma (MM) affects approximately 20,000 Americans annually and remains an incurable hematologic malignancy characterized by frequent early response followed by universal treatment relapse necessitating multiple sequential therapeutic regimens. Until recently, few effective therapies existed. Several novel agents for MM have now become available including the immunomodulatory drugs thalidomide, lenalidomide, as well as the proteasome inhibitor, bortezomib. Each of these agents is undergoing extensive clinical evaluation in combination with other therapies to produce unprecedented response rates in newly diagnosed and relapsed MM. Lenalidomide has proven to be a highly effective treatment agent, particularly when used in combination with dexamethasone but is renally excreted and little information is available about its use in myeloma patients with impaired kidney function (20% have renal failure at some time after diagnosis). Defining a safe and effective dose of lenalidomide to use is a critical step in MM treatment.
OUTLINE: This is a Phase I, dose-escalation study of lenalidomide followed by a Phase II study. Patients are stratified according to degree of renal dysfunction (moderate [creatinine clearance 30-60 mL/min] vs severe [creatinine clearance <30 mL/min and does not require dialysis] vs end-stage renal disease [creatinine clearance <30 mL/min and requires dialysis]).
Patients receive oral lenalidomide on days 1-21 and low-dose oral dexamethasone 40 mg on days 1, 8, 15, and 22. There is a 7 day rest (days 22-28) from lenalidomide. Each cycle is 28 days and repeated in the absence of disease progression or unacceptable toxicity.
Patients enrolled in the phase II portion of the study will undergo blood sample collection periodically for pharmacokinetic analysis of lenalidomide (Mayo Clinic sites only).
After completion of study treatment, patients are followed every 6 months for up to 3 years.
- Diagnosed with previously treated multiple myeloma.
- Measurable disease assessed by one of the following ≤21 days prior to registration:
- Serum monoclonal protein ≥1 g by protein electrophoresis
- Urine monoclonal protein >200 mg on 24 hour electrophoresis
- Serum immunoglobulin free light chain ≥10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
- Monoclonal bone marrow plasmacytosis ≥30% (evaluable disease)
- NOTE: If both serum and urine m-components are present, both must be followed in order to evaluate response.
- All previous cancer therapy including chemotherapy, radiation, hormonal therapy and surgery, must be discontinued ≥2 weeks prior to registration.
- Age ≥18 years.
- ECOG performance status 0-2.
- Acceptable organ and marrow function ≤21 days prior to registration:
- ANC ≥1000/mm³
- Platelet count ≥75,000/mm³
- Total bilirubin ≤2 mg/dL
- AST and ALT ≤3 x upper limit of normal
- Renal impairment at baseline as measured by serum creatinine clearance (CrCl) ≤60 mL/min ≤21 days prior to registration.
- Females of Childbearing Potential (FCBP) must have a negative pregnancy test within 10-14 days and again within 24 hours of starting Cycle 1 and must use an effective double-method contraception for ≥28 days prior to, during, and for ≥28 days after completion of study therapy.
- Able to take required prophylactic anticoagulation.
- Able to understand and willingness to sign a written informed consent.
- Willing to provide blood samples for research purposes (Mayo Clinic sites only).
- If previously received lenalidomide, demonstration of clinical response of any duration or stable disease with progression-free interval of ≥6 months from start of that therapy.
- Concurrent use of other anti-cancer agents or treatments. NOTE: Growth factors and bisphosphonates are allowed as medically indicated. Steroids may be used with an equivalency of up to 20 mg of Prednisone per day as long as the dose has not been adjusted upwards in past 2 weeks prior to study registration.
- Uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing or active infection requiring IV antibiotics
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Uncontrolled cardiac arrhythmia
- Psychiatric illness/social situation that would limit compliance with study requirements.
- Any of the following as this regimen may be harmful to a developing fetus or nursing child:
- Pregnant women
- Breast-feeding women
- Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception.
- HIV-positive patients on combination antiretroviral therapy.
- Known hypersensitivity to thalidomide or other immunomodulatory drugs.
- History of Stevens-Johnson syndrome characterized by a desquamating rash while taking thalidomide or similar drugs.
- Other active malignancy except for non melanoma skin cancer or in situ cervical or breast cancer.
- Concurrent radiation therapy, except for palliation of a single painful bone lesion or fracture.
Trial Lead Organizations/Sponsors
PrECOG, LLCCelgene Corporation
|Joseph R. Mikhael||Study Chair|
|Carolyn Andrews, RN||Ph: 267-207-4070|
|Mayo Clinic Cancer Center|
|Mayo Clinic Clinical Trials Office||Ph: 507-538-7623|
|Suzanne Hayman||Principal Investigator|
|Gundersen Lutheran Center for Cancer and Blood|
|Christine Meyer, CCRP||Ph: 608-775-2837|
|Kurt Oettel, MD||Principal Investigator|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00790842
ClinicalTrials.gov processed this data on October 17, 2013
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