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

NCT00790842 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: PrE1003RV-MM-PrECOG-0394
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 16

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.

Conditions

Multiple Myeloma; Plasma Cell Neoplasm

Keywords

Refractory Multiple Myeloma; Relapsed Multiple Myeloma; Multiple Myeloma with Renal Dysfunction; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Number of Participants in Phase I Component With Dose Limiting Toxicities During the First Cycle of Therapy

  Dose Limiting Toxicity (DLT) was defined as any of the following events determined by the investigator to be possibly, probably, or definitely related to lenalidomide within the first cycle of therapy irrespective of whether the adverse events resolved: * Grade 3 or higher neutropenia with fever ≥38.5 degrees C * Grade 4 neutropenia ≥7 days * Grade 4 or higher thrombocytopenia * Other non-hematologic Grade 4 or higher adverse event not present prior to starting therapy or not due to underlying cause

  First cycle of therapy (28 days)

• Percentage of Participants Who Experience a Response [sCR, CR, VGPR, PR]

  Per International Myeloma Working Group criteria, complete response (CR): negative immunofixation of serum and urine, normalization of free light chain (FLC) ratio if at study entry FLC was only measurable non-bone parameter, \<5% plasma cells in bone marrow, disappearance of any soft tissue plasma cytomas; stringent complete response (sCR): all of above, + normal serum FLC ratio in all patients and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; partial response (PR): \>=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to \< 200 mg per 24 hours, \>=50% decrease in difference between involved and uninvolved FLC levels or a 50% decrease in level of involved FLC with 50% decrease in ratio, \>=50% reduction in bone marrow plasma cells, if baseline percentage was \>=30%, \>=50% reduction in size of soft tissue plasmacytoma; very good partial response (VGPR): PR + improvements in serum and urine M-components

  56 months

Secondary Outcomes (6)

• Overall Survival Time

  56 months

• Duration of Response

  56 months

• Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient

  56 months

• Renal Function Over Time

  56 months

• Pharmacokinetics of Lenalidomide in Impaired Renal Function

  56 months

Study Arms (3)

Group A - CrCl 30-60 mL/min

EXPERIMENTAL

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.

Drug: Lenalidomide; Drug: Dexamethasone; Drug: Anticoagulants

Group B, CrCl < 30 mL/min

EXPERIMENTAL

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.

Drug: Lenalidomide; Drug: Dexamethasone; Drug: Anticoagulants

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

EXPERIMENTAL

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.

Drug: Lenalidomide; Drug: Dexamethasone; Drug: Anticoagulants

Interventions

Lenalidomide 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.

Also known as: Revlimid

Group A - CrCl 30-60 mL/min; Group B, CrCl < 30 mL/min; Group C, CrCl < 30 mL/min, on dialysis

Dexamethasone DRUG

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

Also known as: Decadron

Group A - CrCl 30-60 mL/min; Group B, CrCl < 30 mL/min; Group C, CrCl < 30 mL/min, on dialysis

Anticoagulants 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.

Also known as: Aspirin, Heparin, Low Molecular Weight Heparin, Coumadin

Group A - CrCl 30-60 mL/min; Group B, CrCl < 30 mL/min; Group C, CrCl < 30 mL/min, on dialysis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• PrECOG, LLC.: lead
• Celgene: collaborator

Study Sites (16)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259-5499, United States

Location

Emory University Winship Cancer

Atlanta, Georgia, 30322, United States

Location

University of IL at Chicago

Chicago, Illinois, 60612, United States

Location

McFarland Clinic

Ames, Iowa, 50010, United States

Location

Siouxland Hematology Oncology Associates

Sioux City, Iowa, 51101, United States

Location

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

Ann Arbor, Michigan, 48106-0955, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Metro MN CCOP

Saint Louis Park, Minnesota, 55416, United States

Location

Missouri Valley Cancer Consortium

Omaha, Nebraska, 68106, United States

Location

Kinston Medical Specialists

Kinston, North Carolina, 28501, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4283, United States

Location

Reading Hospital and Medical Center

West Reading, Pennsylvania, 19611, United States

Location

WVU Mary Babb Randolph Cancer Center

Morgantown, West Virginia, 26506, United States

Location

Gundersen Lutheran

La Crosse, Wisconsin, 54601, United States

Location

Waukesha Memorial Hospital (ProHealth Care)

Waukesha, Wisconsin, 53188, United States

Location

Aurora Cancer Center

Wauwatosa, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 30190454 RESULT

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Lenalidomide; Dexamethasone; Calcium Dobesilate; Anticoagulants; Aspirin; Heparin; Heparin, Low-Molecular-Weight; Warfarin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Hematologic Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Salicylates; Hydroxybenzoates; Phenols; Glycosaminoglycans; Polysaccharides; Carbohydrates; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans

Results Point of Contact

• Title: PrECOG Statistician
• Organization: PrECOG

jbmanola@gmail.com

978-835-3516

Study Officials

• Joseph R. Mikhael, MD

  Mayo Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2008
• First Posted: November 14, 2008
• Study Start: January 21, 2009
• Primary Completion: September 30, 2017
• Study Completion: March 8, 2018
• Last Updated: October 24, 2018
• Results First Posted: October 24, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)