Lenalidomide and Low-Dose Dexamethasone in Patients With Previously Treated Multiple Myeloma and Kidney Dysfunction (PrE1003)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
PrECOG, LLC.
ClinicalTrials.gov Identifier:
NCT00790842
First received: November 13, 2008
Last updated: February 3, 2016
Last verified: February 2016
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Plasma Cell Neoplasm
Drug: Group A=30-60 CrCl (mL/min)
Drug: Group B=CrCL<30 mL/min not on dialysis
Drug: Group C=CrCL<30 mL/min and on dialysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of the Tolerability of Lenalidomide and Low Dose Dexamethasone in Previously Treated Multiple Myeloma Patients With Impaired Renal Function

Resource links provided by NLM:


Further study details as provided by PrECOG, LLC.:

Primary Outcome Measures:
  • Maximum tolerated dose of lenalidomide (Phase I) [ Time Frame: 15 months ] [ Designated as safety issue: Yes ]
    Phase I-Establish the maximum tolerated dose of lenalidomide in each of three groups of myeloma patients with impaired renal function.

  • Assess response rate (Phase II) [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    Phase II- Assess the efficacy (response rate [CR, sCR, VGPR, PR]) of this combination across the three groups of myeloma patients with impaired renal function.


Secondary Outcome Measures:
  • Survival time [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    To describe the overall survival and progression-free survival of myeloma patients with impaired renal function treated with lenalidomide and dexamethasone.

  • Duration of response [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    To describe the duration of response and time to treatment failure of myeloma patients with impaired renal function treated with lenalidomide and dexamethasone.

  • Safety profile [ Time Frame: 56 months ] [ Designated as safety issue: Yes ]
    To evaluate the safety profile of lenalidomide given in combination with weekly dexamethasone in myeloma patients with impaired renal function.

  • Renal function over time [ Time Frame: 56 months ] [ Designated as safety issue: Yes ]
    To describe renal function over time and to evaluate the safety profile of a onetime increase in lenalidomide dose at least 2 cycles after start of treatment due to improved renal function.

  • Pharmacokinetics of lenalidomide in impaired renal function [ Time Frame: 56 months ] [ Designated as safety issue: No ]
    To determine the pharmacokinetics of lenalidomide administration in myeloma patients with impaired renal function (pharmacokinetic analysis will be performed in up to 12 consented Mayo Clinic subjects treated during the Phase II component of the trial (only).


Enrollment: 62
Study Start Date: December 2008
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Group A=30-60 CrCl (mL/min)
Lenalidomide days 1-21 and Dexamethasone 40 mg days 1, 8, 15 and 22 every 28 days. Phase I will determine the dose of lenalidomide to be used in Phase II.
Drug: Group A=30-60 CrCl (mL/min)
Each Cycle=28 days. Lenalidomide by mouth days 1-21 and Dexamethasone 40 mg by mouth days 1, 8, 15 and 22. There is a 7 day rest (days 22-28) from lenalidomide. Continue until disease progression or unacceptable toxicity. Phase I will determine the dose of lenalidomide to be used in Phase II.
Other Names:
  • Revlimid
  • Immunomodulatory
  • Decadron
Group B=CrCL<30 mL/min not on dialysis
Lenalidomide days 1-21 and Dexamethasone 40 mg days 1, 8, 15 and 22 every 28 days. Phase I will determine the dose of lenalidomide to be used in Phase II.
Drug: Group B=CrCL<30 mL/min not on dialysis
Each Cycle=28 days. Lenalidomide by mouth days 1-21 and Dexamethasone 40 mg by mouth days 1, 8, 15 and 22. There is a 7 day rest (days 22-28) from lenalidomide. Continue until disease progression or unacceptable toxicity. Phase I will determine the dose of lenalidomide to be used in Phase II.
Other Names:
  • Revlimid
  • Immunomodulatory
  • Decadron
Group C=CrCL<30 mL/min and on dialysis
Lenalidomide days 1-21 and Dexamethasone 40 mg days 1, 8, 15 and 22 every 28 days. Phase I will determine the dose of lenalidomide to be used in Phase II.
Drug: Group C=CrCL<30 mL/min and on dialysis

Each Cycle=28 days. Lenalidomide by mouth days 1-21 and Dexamethasone 40 mg by mouth days 1, 8, 15 and 22. There is a 7 day rest (days 22-28) from lenalidomide. Continue until disease progression or unacceptable toxicity. Phase I will determine the dose of lenalidomide to be used in Phase II.

Dialysis includes hemodialysis or peritoneal dialysis. When lenalidomide and/or dexamethasone treatment occurs on a dialysis day, lenalidomide and/or dexamethasone must be taken after dialysis.

Other Names:
  • Revlimid
  • Immunomodulatory
  • Decadron

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
    • 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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00790842

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259-5499
United States, Georgia
Emory University Winship Cancer
Atlanta, Georgia, United States, 30322
United States, Illinois
University of IL at Chicago
Chicago, Illinois, United States, 60612
United States, Iowa
McFarland Clinic
Ames, Iowa, United States, 50010
Siouxland Hematology Oncology Associates
Sioux City, Iowa, United States, 51101
United States, Michigan
Michigan Cancer Research Consortium and Oncology Research- St. Joseph Mercy Hospital - Ann Arbor
Ann Arbor, Michigan, United States, 48106-0955
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Metro MN CCOP
St. Louis Park, Minnesota, United States, 55416
United States, Nebraska
Missouri Valley Cancer Consortium
Omaha, Nebraska, United States, 68106
United States, North Carolina
Kinston Medical Specialists
Kinston, North Carolina, United States, 28501
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
Reading Hospital and Medical Center
West Reading, Pennsylvania, United States, 19611
United States, West Virginia
WVU Mary Babb Randolph Cancer Center
Morgantown, West Virginia, United States, 26506
United States, Wisconsin
Gundersen Lutheran
La Crosse, Wisconsin, United States, 54601
Waukesha Memorial Hospital (ProHealth Care)
Waukesha, Wisconsin, United States, 53188
Aurora Cancer Center
Wauwatosa, Wisconsin, United States, 53226
Sponsors and Collaborators
PrECOG, LLC.
Celgene Corporation
Investigators
Study Chair: Joseph R. Mikhael, MD Mayo Clinic
  More Information

Publications:
Responsible Party: PrECOG, LLC.
ClinicalTrials.gov Identifier: NCT00790842     History of Changes
Other Study ID Numbers: PrE1003  RV-MM-PrECOG-0394 
Study First Received: November 13, 2008
Last Updated: February 3, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by PrECOG, LLC.:
Refractory Multiple Myeloma
Relapsed Multiple Myeloma
Multiple Myeloma with Renal Dysfunction
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Lenalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents

ClinicalTrials.gov processed this record on February 04, 2016