Lenalidomide and Dexamethasone With or Without Thalidomide in Treating Patients With Multiple Myeloma - Full Text View

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00098475

Purpose

RATIONALE: Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Lenalidomide and thalidomide may also stop the growth of multiple myeloma by blocking blood flow to the cancer. 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, thalidomide, and dexamethasone together may kill more cancer cells.

PURPOSE: This randomized phase III trial is studying lenalidomide and low-dose dexamethasone to see how well it works compared to lenalidomide and standard-dose dexamethasone, given with or without thalidomide, in treating patients with multiple myeloma.

Condition	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: acetylsalicylic acid Drug: dexamethasone Drug: lenalidomide Drug: thalidomide	Phase III

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Randomized Phase III Study of CC-5013 Plus Dexamethasone Versus CC-5013 Plus Low Dose Dexamethasone in Multiple Myeloma With Thalidomide Plus Dexamethasone Salvage Therapy for Non-Responders

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

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

U.S. FDA Resources

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

Primary Outcome Measures:

Comparison of treatment regimens [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity [ Designated as safety issue: Yes ]
Response rate [ Designated as safety issue: No ]

Estimated Enrollment:	412
Study Start Date:	October 2004

Detailed Description:

OBJECTIVES:

Primary

Compare the response rate in patients with newly diagnosed multiple myeloma treated with lenalidomide and standard-dose vs low-dose dexamethasone.
Compare the toxicity of these regimens in these patients.

Secondary

Determine the response rate in patients who do not achieve an objective response at any point during the first 4 courses of lenalidomide and dexamethasone and are subsequently treated with salvage therapy comprising thalidomide and dexamethasone.
Determine the efficacy of aspirin (325 mg/day) versus warfarin (dose adjusted to maintain a target INR of 2-3) in preventing deep vain thrombosis in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral lenalidomide once daily on days 1-21, oral acetylsalicyclic acid (or other deep vein thrombosis prophylaxis at the discretion of the principal investigator) once daily on days 1-28, and standard-dose oral dexamethasone once daily on days 1-4, 9-12, and 17-20.
Arm II: Patients receive oral lenalidomide and acetylsalicyclic acid as in arm I and low-dose oral dexamethasone once daily on days 1, 8, 15, and 22.

In both arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients not responding at any point during the first 4 courses of lenalidomide and dexamethasone are assigned to 1 of 2 salvage therapy arms. Patients who progress during treatment on arms I or II have the option to register on salvage therapy arms III or IV respectively.

Arm III (patients with no response after treatment on arm I): Patients receive oral thalidomide once daily on days 1-28 and standard-dose oral dexamethasone once daily on days 1-4, 9-12, and 17-20.
Arm IV (patients with no response after treatment on arm II): Patients receive oral thalidomide as in arm III and low-dose oral dexamethasone once daily on days 1, 8, 15, and 22.

In both salvage therapy arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. After completion of 4 courses of therapy, patients may undergo stem cell harvest (using growth factors only) for cryopreservation.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 412 patients (206 per treatment arm) will be accrued for this study within 24 months.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of multiple myeloma within the past 90 days, confirmed by the following criteria:
- Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells OR biopsy-proven plasmacytoma within the past 4 weeks
- Measurable monoclonal protein ≥ 1.0 g/dL by serum protein electrophoresis OR monoclonal light chain ≥ 200 mg by 24-hour urine protein electrophoresis within the past 4 weeks
Symptomatic disease
Prior plasmacytoma treated with curative-intent radiotherapy allowed provided disease progressed to active multiple myeloma
No smoldering myeloma
No monoclonal gammopathy of undetermined significance

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

Not specified

Hematopoietic

Hemoglobin > 7 g/dL
Platelet count > 75,000/mm^3
Absolute neutrophil count > 1,000/mm^3

Hepatic

Bilirubin ≤ 1.5 mg/dL
ALT and AST ≤ 2.5 times upper limit of normal (ULN)

Renal

Creatinine < 2.5 mg/dL

Cardiovascular

No uncontrolled hypertension
No uncontrolled cardiac arrhythmia
No symptomatic congestive heart failure
No unstable angina
No prior or concurrent deep vein thrombosis

Pulmonary

No prior or concurrent pulmonary embolism

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective double-method contraception (1 highly effective and one additional method) for 4 weeks prior, during, and for 4 weeks after completion of study treatment
No other active malignancy
- Prior malignancy with a low expectation of recurrence within the next 6 months allowed
No prior Stevens Johnson syndrome
No active uncontrolled seizure disorder
- No seizures within the past 6 months
No active uncontrolled infection
No uncontrolled psychiatric illness or social situation that would preclude study compliance
No peripheral neuropathy ≥ grade 2 due to other medical conditions
No other uncontrolled illness
Patients must be willing and able to take antithrombosis prophylaxis
Patients must

PRIOR CONCURRENT THERAPY:

Biologic therapy

No concurrent sargramostim (GM-CSF)

Chemotherapy

Not specified

Endocrine therapy

No prior glucocorticosteroid therapy for multiple myeloma
The following treatments for non-malignant disorders are allowed:
- Prior systemic glucocorticosteroids
- Prior or concurrent topical or localized glucocorticosteroids
- Concurrent systemic glucocorticosteroids at a dose of ≤ 10 mg of prednisone per day (or equivalent)

Radiotherapy

See Disease Characteristics
At least 4 weeks since prior palliative and/or localized radiotherapy

Surgery

Not specified

Other

No prior systemic therapy for multiple myeloma except bisphosphonates

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00098475

Show 243 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	S. V. Rajkumar, MD	Mayo Clinic
Investigator:	Rafael Fonseca, MD	Mayo Clinic

More Information

Additional Information:

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

Publications:

Jacobus S, Kumar S, Callander NS, et al.: Effect of venous thrombotic events on overall survival in multiple myeloma: analysis of thrombotic events occurring in E4A03: A randomized trial of lenalidomide plus high-dose dexamethasone (RD) versus lenalidomide plus low-dose dexamethasone (Rd) in newly diagnosed multiple myeloma, a trial coordinated by the Eastern Cooperative Oncology Group (ECOG). [Abstract] Blood 112 (11): A-1740, 2008.

Rajkumar SV, Jacobus S, Callander N, et al.: A randomized phase III trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): a trial coordinated by the Eastern Cooperative Oncology Group. [Abstract] Blood 108 (11): A-799, 2006.

Ballester O. The emperor's new clothes or the current practice of clinical trials for multiple myeloma in the USA. Cancer Invest. 2008 Jun;26(5):445-7.

Study ID Numbers:	CDR0000404161, ECOG-E4A03
Study First Received:	December 7, 2004
Last Updated:	January 10, 2009
ClinicalTrials.gov Identifier:	NCT00098475 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Dexamethasone
Anti-Inflammatory Agents
Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Hematologic Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Fibrin Modulating Agents
Hemorrhagic Disorders
Therapeutic Uses
Cardiovascular Diseases
Angiogenesis Modulating Agents
Immunoproliferative Disorders

Immune System Diseases
Antineoplastic Agents, Hormonal
Hematologic Diseases
Cyclooxygenase Inhibitors
Glucocorticoids
Multiple Myeloma
Neoplasms
Platelet Aggregation Inhibitors
Leprostatic Agents
Thalidomide
Immunologic Factors
Blood Protein Disorders
Antineoplastic Agents
Paraproteinemias
Fibrinolytic Agents

ClinicalTrials.gov processed this record on February 08, 2010