Lenalidomide and Low-Dose Dexamethasone in Patients With Previously Treated Multiple Myeloma and Kidney Dysfunction

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase II, Phase IBiomarker/Laboratory analysis, Treatment18 and overPrE1003
NCI-2014-02113, RV-MM-PrECOG-0394, MAYO-MC0885, MC0885, MAYO-08-003156, CELGENE-RV-MM-PI-0394, NCT00790842

Trial Description

Summary

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.

Eligibility Criteria

Inclusion Criteria:

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.

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

ANC ≥1000/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.

Exclusion Criteria:

Concurrent radiation therapy, except for palliation of a single painful bone lesion

or fracture.

Other active malignancy except for non melanoma skin cancer or in situ cervical or

breast cancer.

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.

Breast-feeding women

Pregnant women

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

child:

Psychiatric illness/social situation that would limit compliance with study

requirements.

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

following:

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

PrECOG, LLC

  • Celgene Corporation

Trial Sites

U.S.A.

Pennsylvania
Philadelphia

University of Pennsylvania/Abramson Cancer Center

Brendan Weiss
Principal Investigator

See All Trial Sites

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.