Lenalidomide and Low-Dose Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma and Kidney Dysfunction - Full Text View

Sponsors and Collaborators:	Mayo Clinic Scottsdale National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00790842

Purpose

RATIONALE: 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.

PURPOSE: This phase I/II trial is studying the side effects and best dose of lenalidomide when given together with low-dose dexamethasone and to see how well they work in treating patients with relapsed or refractory multiple myeloma and kidney dysfunction.

Condition	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: dexamethasone Drug: lenalidomide Procedure: pharmacological study	Phase I Phase II

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

Drug Information available for: Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus Lenalidomide CC 5013

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I/II Study of the Tolerability of Lenalidomide and Low Dose Dexamethasone in Multiple Myeloma Patients With Impaired Renal Function.

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose of lenalidomide (Phase I) [ Designated as safety issue: Yes ]
Toxicity profile as assessed by NCI CTCAE v3.0 (Phase I) [ Designated as safety issue: Yes ]
Time to any treatment-related toxicity, treatment-related grade 3+ toxicity, and hematologic nadirs (WBC, ANC, and platelet counts) (Phase I) [ Designated as safety issue: Yes ]
Time to progression and time to treatment failure (Phase I) [ Designated as safety issue: No ]
Proportion of patients with at least partial response (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Survival time (Phase II) [ Designated as safety issue: No ]
Progression-free survival time (Phase II) [ Designated as safety issue: No ]
Duration of response (Phase II) [ Designated as safety issue: No ]
Time to treatment failure (Phase II) [ Designated as safety issue: No ]
Adverse events (Phase II) [ Designated as safety issue: Yes ]

Estimated Enrollment:	135
Study Start Date:	December 2008
Estimated Primary Completion Date:	November 2011 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To establish the maximum tolerated dose of lenalidomide when administered in combination with low-dose dexamethasone in patients with relapsed or refractory multiple myeloma and varying degrees of renal dysfunction. (Phase I)
To assess the efficacy of this regimen, in terms of response rate (complete response [CR], stringent CR, partial response [PR], and very good PR), in these patients. (Phase II)

Secondary

To describe the overall survival, progression-free survival, duration of response, and time to treatment failure in these patients.
To evaluate the safety profile of this regimen in these patients.
To determine the pharmacokinetics of lenalidomide in these patients. (Phase II)

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 30-50 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 on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients enrolled in the phase II portion of the study undergo blood sample collection periodically for pharmacokinetic analysis of lenalidomide.

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

DISEASE CHARACTERISTICS:

Diagnosis of symptomatic multiple myeloma
- Relapsed or refractory disease
Measurable or evaluable disease, as defined by one of the following:
- Serum monoclonal protein ≥ 1.0 g by protein electrophoresis
- Urine monoclonal protein > 200 mg by 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
Must have renal dysfunction at baseline (i.e., creatinine clearance ≤ 50 mL/min)

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy ≥ 6 months
ANC ≥ 1,000/mm^3
Platelet count ≥ 75,000/mm^3
Total bilirubin ≤ 2.0 mg/dL
AST and ALT ≤ 3 times upper limit of normal
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective double-method contraception for ≥ 28 days prior to, during, and for ≥ 28 days after completion of study therapy
Willing to provide blood samples for research purposes
Able to take prophylactic anticoagulation
No concurrent uncontrolled 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 or social situation that would limit compliance with study requirements
No other active malignancy except for nonmelanoma skin cancer or in situ cervical or breast cancer
No known hypersensitivity or prior intolerance to thalidomide
No development of Stevens-Johnson syndrome characterized by a desquamating rash while taking thalidomide or similar drugs

PRIOR CONCURRENT THERAPY:

Prior lenalidomide allowed provided the patient demonstrated clinical response of any duration OR stable disease with progression-free interval of ≥ 6 months from the start of therapy
At least 2 weeks since prior chemotherapy, radiotherapy, hormonal therapy, or surgery for cancer
No concurrent radiotherapy except for the palliation of a single painful bone lesion or fracture
No other concurrent anticancer agents or treatments except for the following:
- Prednisone at stable doses of ≤ 20 mg/day (i.e., dose has not been adjusted upwards within the past 2 weeks)
- Growth factors or bisphosphonates as medically indicated
No concurrent combination antiretroviral therapy for HIV-positive patients

Contacts and Locations

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

Locations

United States, Arizona
Mayo Clinic Scottsdale	Recruiting
Scottsdale, Arizona, United States, 85259-5499
Contact: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623
United States, Minnesota
Mayo Clinic Cancer Center	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623

Sponsors and Collaborators

Mayo Clinic Scottsdale

National Cancer Institute (NCI)

Investigators

Study Chair:	Joseph R. Mikhael, MD	Mayo Clinic Scottsdale
Investigator:	Suzanne Hayman, MD	Mayo Clinic

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Responsible Party:	Mayo Clinic Scottsdale ( Clinical Trials Office )
Study ID Numbers:	CDR0000617813, MAYO-MC0885, MAYO-08-003156, CELGENE-RV-MM-PI-0394
Study First Received:	November 13, 2008
Last Updated:	December 31, 2008
ClinicalTrials.gov Identifier:	NCT00790842
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Study placed in the following topic categories:

Dexamethasone
Immunoproliferative Disorders
Blood Protein Disorders
Hematologic Diseases
Blood Coagulation Disorders
Lenalidomide
Vascular Diseases
Paraproteinemias

Hemostatic Disorders
Multiple Myeloma
Hemorrhagic Disorders
Multiple myeloma
Lymphoproliferative Disorders
Dexamethasone acetate
Neoplasms, Plasma Cell

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Gastrointestinal Agents
Antiemetics

Hormones
Glucocorticoids
Pharmacologic Actions
Neoplasms
Autonomic Agents
Therapeutic Uses
Cardiovascular Diseases
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009