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A Phase I/II Study of the Tolerability of Lenalidomide and Low Dose Dexamethasone in Previously Treated Multiple Myeloma Patients With Impaired Renal Function

Phase 1/Phase 2
18 Years
Open (Enrolling)
Multiple Myeloma, Plasma Cell Neoplasm

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Trial Information

A Phase I/II Study of the Tolerability of Lenalidomide and Low Dose Dexamethasone in Previously Treated Multiple Myeloma Patients With Impaired Renal Function

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.

Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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

- 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

- Any of the following as this regimen may be harmful to a developing fetus or nursing

- 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.

Type of Study:


Study Design:

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

Outcome Measure:

Maximum tolerated dose of lenalidomide (Phase I)

Outcome Description:

Phase I-Establish the maximum tolerated dose of lenalidomide in each of three groups of myeloma patients with impaired renal function.

Outcome Time Frame:

15 months

Safety Issue:


Principal Investigator

Joseph R. Mikhael, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

December 2008

Completion Date:

January 2016

Related Keywords:

  • Multiple Myeloma
  • Plasma Cell Neoplasm
  • Refractory Multiple Myeloma
  • Relapsed Multiple Myeloma
  • Multiple Myeloma with Renal Dysfunction
  • Stage I Multiple Myeloma
  • Stage II Multiple Myeloma
  • Stage III Multiple Myeloma
  • Neoplasms
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma



Mayo ClinicRochester, Minnesota  55905
Marquette General HospitalMarquette, Michigan  49855
Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
Hackensack University Medical CenterHackensack, New Jersey  07601
Kinston Medical SpecialistsKinston, North Carolina  28501
Mayo Clinic in ArizonaScottsdale, Arizona  85259-5404
University of PennsylvaniaPhiladelphia, Pennsylvania  19104
McFarland ClinicAmes, Iowa  50010
Gundersen LutheranLa Crosse, Wisconsin  54601
Metro MN CCOPMinneapolis, Minnesota  55416
Siouxland Hematology Oncology AssociatesSioux City, Iowa  51101
Missouri Valley Cancer ConsortiumOmaha, Nebraska  68106
Emory University Winship CancerAtlanta, Georgia  30322
University of IL at ChicagoChicago, Illinois  60612
WVU Mary Babb Randolph Cancer CenterMorgantown, West Virginia  26506
Waukesha Memorial Hospital (ProHealth Care)Waukesha, Wisconsin  53188
Michigan Cancer Research Consortium and Oncology Research- St. Joseph Mercy Hospital - Ann ArborAnn Arbor, Michigan  48106-0955