Lenalidomide and Low-Dose Dexamethasone in Patients With Previously Treated Multiple Myeloma and Kidney Dysfunction
Basic Trial Information
|Phase II, Phase I||Biomarker/Laboratory analysis, Treatment||18 and over||PrE1003|
NCI-2014-02113, 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
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.
If previously received lenalidomide, demonstration of clinical response of any
duration or stable disease with progression-free interval of ≥6 months from start of
Willing to provide blood samples for research purposes (Mayo Clinic sites only).
Able to understand and willingness to sign a written informed consent.
Able to take required prophylactic anticoagulation.
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.
Renal impairment at baseline as measured by serum creatinine clearance (CrCl) ≤60
mL/min ≤21 days prior to registration.
AST and ALT ≤3 x upper limit of normal
Total bilirubin ≤2 mg/dL
Platelet count ≥75,000/mm³
Acceptable organ and marrow function ≤21 days prior to registration:
ECOG performance status 0-2.
Age ≥18 years.
All previous cancer therapy including chemotherapy, radiation, hormonal therapy and
surgery, must be discontinued ≥2 weeks prior to registration.
NOTE: If both serum and urine m-components are present, both must be followed in
order to evaluate response.
Monoclonal bone marrow plasmacytosis ≥30% (evaluable disease)
Serum immunoglobulin free light chain ≥10 mg/dL AND abnormal serum
immunoglobulin kappa to lambda free light chain ratio
Urine monoclonal protein >200 mg on 24 hour electrophoresis
Serum monoclonal protein ≥1 g by protein electrophoresis
Measurable disease assessed by one of the following ≤21 days prior to registration:
Diagnosed with previously treated multiple myeloma.
Concurrent radiation therapy, except for palliation of a single painful bone lesion
Other active malignancy except for non melanoma skin cancer or in situ cervical or
History of Stevens-Johnson syndrome characterized by a desquamating rash while taking
thalidomide or similar drugs.
Known hypersensitivity to thalidomide or other immunomodulatory drugs.
HIV-positive patients on combination antiretroviral therapy.
Men or women of childbearing potential or their sexual partners who are
unwilling to employ adequate contraception.
Any of the following as this regimen may be harmful to a developing fetus or nursing
Psychiatric illness/social situation that would limit compliance with study
Uncontrolled cardiac arrhythmia
Unstable angina pectoris
Symptomatic congestive heart failure
Ongoing or active infection requiring IV antibiotics
Uncontrolled intercurrent illness including, but not limited to, any of the
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.
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
- Celgene Corporation
University of Pennsylvania/Abramson Cancer Center
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00790842
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.