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

NCT ID: NCT00790842

Last Updated: 2018-10-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-21
• Study Completion Date: 2018-03-08

Brief 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.

Detailed Description

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.

Conditions

Multiple Myeloma; Plasma Cell Neoplasm

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A - CrCl 30-60 mL/min

Creatinine clearance 30 - 60 mL/min, lenalidomide dose determined in phase I, dexamethasone 40 mg orally days 1, 8, 15 and 22 of a 28 day cycle, and anticoagulants.

Group Type: EXPERIMENTAL

Lenalidomide

Intervention Type: DRUG

Given by mouth days 1-21 of a 28-day cycle. There is a 7 day rest (days 22-28). Continue until disease progression or unacceptable toxicity.

Dexamethasone

Intervention Type: DRUG

40 mg given by mouth days 1, 8, 15 and 22 of a 28-day cycle. Continue until disease progression or unacceptable toxicity.

Anticoagulants

Intervention Type: DRUG

Anticoagulation consisted of aspirin at either 81 mg/day or 325 mg/day at the physician's discretion. Heparin, low molecular weight heparin, or coumadin could be used if the patient was intolerant to aspirin.

Group B, CrCl < 30 mL/min

Creatinine clearance \< 30 mL/min, not on dialysis, lenalidomide dose determined in phase I, dexamethasone 40 mg orally days 1, 8, 15 and 22 of a 28 day cycle, and anticoagulants.

Group Type: EXPERIMENTAL

Lenalidomide

Intervention Type: DRUG

Given by mouth days 1-21 of a 28-day cycle. There is a 7 day rest (days 22-28). Continue until disease progression or unacceptable toxicity.

Dexamethasone

Intervention Type: DRUG

40 mg given by mouth days 1, 8, 15 and 22 of a 28-day cycle. Continue until disease progression or unacceptable toxicity.

Anticoagulants

Intervention Type: DRUG

Anticoagulation consisted of aspirin at either 81 mg/day or 325 mg/day at the physician's discretion. Heparin, low molecular weight heparin, or coumadin could be used if the patient was intolerant to aspirin.

Group C, CrCl < 30 mL/min, on dialysis

Creatinine clearance \< 30 mL/min and on dialysis, lenalidomide dose determined in phase I, dexamethasone 40 mg orally days 1, 8, 15 and 22 of a 28 day cycle, and anticoagulants.

Group Type: EXPERIMENTAL

Lenalidomide

Intervention Type: DRUG

Given by mouth days 1-21 of a 28-day cycle. There is a 7 day rest (days 22-28). Continue until disease progression or unacceptable toxicity.

Dexamethasone

Intervention Type: DRUG

40 mg given by mouth days 1, 8, 15 and 22 of a 28-day cycle. Continue until disease progression or unacceptable toxicity.

Anticoagulants

Intervention Type: DRUG

Anticoagulation consisted of aspirin at either 81 mg/day or 325 mg/day at the physician's discretion. Heparin, low molecular weight heparin, or coumadin could be used if the patient was intolerant to aspirin.

Interventions

Lenalidomide

Given by mouth days 1-21 of a 28-day cycle. There is a 7 day rest (days 22-28). Continue until disease progression or unacceptable toxicity.

Intervention Type: DRUG

Dexamethasone

40 mg given by mouth days 1, 8, 15 and 22 of a 28-day cycle. Continue until disease progression or unacceptable toxicity.

Intervention Type: DRUG

Anticoagulants

Anticoagulation consisted of aspirin at either 81 mg/day or 325 mg/day at the physician's discretion. Heparin, low molecular weight heparin, or coumadin could be used if the patient was intolerant to aspirin.

Intervention Type: DRUG

Other Intervention Names

Revlimid; Decadron; Aspirin; Heparin; Low Molecular Weight Heparin; Coumadin

Eligibility Criteria

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)
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Acceptable organ and marrow function ≤21 days prior to registration:

• Absolute neutrophil count (ANC) ≥1000/mm³
• Platelet count ≥75,000/mm³
• Total bilirubin ≤2 mg/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (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. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: collaborator

PrECOG, LLC.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph R. Mikhael, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Emory University Winship Cancer

Atlanta, Georgia, United States

University of IL at Chicago

Chicago, Illinois, United States

McFarland Clinic

Ames, Iowa, United States

Siouxland Hematology Oncology Associates

Sioux City, Iowa, United States

Michigan Cancer Research Consortium and Oncology Research- St. Joseph Mercy Hospital - Ann Arbor

Ann Arbor, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Metro MN CCOP

Saint Louis Park, Minnesota, United States

Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

Kinston Medical Specialists

Kinston, North Carolina, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Reading Hospital and Medical Center

West Reading, Pennsylvania, United States

WVU Mary Babb Randolph Cancer Center

Morgantown, West Virginia, United States

Gundersen Lutheran

La Crosse, Wisconsin, United States

Waukesha Memorial Hospital (ProHealth Care)

Waukesha, Wisconsin, United States

Aurora Cancer Center

Wauwatosa, Wisconsin, United States

Countries

United States

References

Mikhael J, Manola J, Dueck AC, Hayman S, Oettel K, Kanate AS, Lonial S, Rajkumar SV. Lenalidomide and dexamethasone in patients with relapsed multiple myeloma and impaired renal function: PrE1003, a PrECOG study. Blood Cancer J. 2018 Aug 29;8(9):86. doi: 10.1038/s41408-018-0110-7.

Reference Type: RESULT

PMID: 30190454 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

RV-MM-PrECOG-0394

Identifier Type: OTHER

Identifier Source: secondary_id

PrE1003

Identifier Type: -

Identifier Source: org_study_id