Lenalidomide With or Without Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma

NCT ID: NCT00772915

Last Updated: 2020-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-03
• Study Completion Date: 2018-06-27

Brief Summary

RATIONALE: Lenalidomide and dexamethasone may stop the growth of multiple myeloma by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well lenalidomide works with or without dexamethasone in treating patients with newly diagnosed multiple myeloma.

Detailed Description

OBJECTIVES:

Primary

• To assess the progression-free survival at 1 year in patients with newly diagnosed symptomatic multiple myeloma treated with lenalidomide alone or in combination with dexamethasone added for disease progression or lack or partial response.

Secondary

• To assess the response rate of this regimen in these patients.
• To assess the toxicity of this regimen in these patients.

Tertiary

• To examine the effect of lenalidomide alone on tumor specific immunity and global parameters of immune function.
• To examine the effect of dexamethasone addition in patients requiring steroids.
• To correlate changes in parameters of immune response and measures of disease response.
• To examine the antiangiogenic activity of lenalidomide alone and in combination with dexamethasone.
• To examine the effect of lenalidomide alone on tumor cell survival and proliferation.

OUTLINE: Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for up to 18 courses in the absence of second disease progression or unacceptable toxicity. Beginning in course 4, patients experiencing stable or progressive disease also receive concurrent oral dexamethasone once daily on days 1, 8, 15, and 22 and for all subsequent courses.

Blood and bone marrow samples are collected periodically for pharmacological and correlative studies. Samples are analyzed for parameters of immune activation, cell proliferation and apoptosis, and circulating tumor cells and endothelial cells via flow cytometry; global impact of therapy on immune cell subsets via immunophenotype analysis; and angiogenesis via CD34 staining.

After completion of study therapy, patients are followed periodically for up to 2 years.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lenalidomide with On-Demand Dexamethasone

Lenalidmoide: 25mg once daily orally with food on days 1-21 of 28 day cycle until progression or to a maximum of 18 cycles.

Dexamethasone: 10-40 mg once weekly (days 1, 8, 15, & 22) orally with food until progression.

Group Type: EXPERIMENTAL

dexamethasone

Intervention Type: DRUG

Dose: -40 mg once weekly (days 1, 8, 15, & 22) orally with food until progression.

If after 3 cycles, a partial response is not achieved on lenalidomide alone, dexamethasone 10 mg weekly will be added, and the weekly dexamethasone dose will be increased by 10 mg each cycle to a maximum of 40 mg weekly, as long as a partial response is not achieved. If a partial response is achieved at a dose of dexamethasone less than 40 mg weekly, patients will continue on that dose. If progression at any time, increase dexamethasone to 40 mg weekly. Patient will go off study only when progression is documented while receiving 40 mg/week of dexamethasone or the maximum tolerated dose of dexamethasone (if prior dose reductions have been implemented for toxicity). Increases in dexamethasone dose are to be made only at the initiation of a cycle.

If progression at any time while on lenalidomide alone (first 3 cycles), add dexamethasone 40 mg weekly.

lenalidomide

Intervention Type: DRUG

25mg once daily orally with food on days 1-21 of 28 day cycle until progression or to a maximum of 18 cycles.

Lenalidomide alone will be administered for the first 3 cycles, then in combination with dexamethasone as needed (described).

Interventions

dexamethasone

Dose: -40 mg once weekly (days 1, 8, 15, & 22) orally with food until progression.

If after 3 cycles, a partial response is not achieved on lenalidomide alone, dexamethasone 10 mg weekly will be added, and the weekly dexamethasone dose will be increased by 10 mg each cycle to a maximum of 40 mg weekly, as long as a partial response is not achieved. If a partial response is achieved at a dose of dexamethasone less than 40 mg weekly, patients will continue on that dose. If progression at any time, increase dexamethasone to 40 mg weekly. Patient will go off study only when progression is documented while receiving 40 mg/week of dexamethasone or the maximum tolerated dose of dexamethasone (if prior dose reductions have been implemented for toxicity). Increases in dexamethasone dose are to be made only at the initiation of a cycle.

If progression at any time while on lenalidomide alone (first 3 cycles), add dexamethasone 40 mg weekly.

Intervention Type: DRUG

lenalidomide

25mg once daily orally with food on days 1-21 of 28 day cycle until progression or to a maximum of 18 cycles.

Lenalidomide alone will be administered for the first 3 cycles, then in combination with dexamethasone as needed (described).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Newly diagnosed multiple myeloma, meeting the following criteria:

• Symptomatic disease
• Previously untreated disease
• Measurable or evaluable disease, defined by ≥ 1 of the following:

• Serum monoclonal protein ≥ 1.0 g/dL
• Monoclonal protein > 200 mg by 24-hour urine electrophoresis
• Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa:lambda free light chain ratio
• Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease)
• Measurable soft tissue plasmacytoma, not previously radiated
• No monoclonal gammopathy of unknown significance or asymptomatic myeloma

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 (PS 3 allowed if secondary to pain)
• ANC ≥ 1,500/μL
• Platelet count ≥ 75,000/μL
• Creatinine ≤ 2.0 mg/dL
• Total bilirubin ≤ 1.5 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 2 effective forms of contraception 28 days prior to, during and 28 days after study treatment
• Registered into the RevAssist® program and willing to comply with program requirements
• Able to take prophylactic aspirin (325 mg/day) or warfarin or low molecular weight heparin
• Willing to provide mandatory blood and bone marrow samples
• Willing to return for follow up
• No uncontrolled infection
• No NYHA class III or IV heart failure
• No active deep vein thrombosis that has not been therapeutically anticoagulated
• No known hypersensitivity to thalidomide
• No known HIV positivity
• No known hepatitis type A, B, or C infection
• No other prior active malignancy within the past 2 years, except currently treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast
• No development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs

PRIOR CONCURRENT THERAPY:

• At least 3 weeks since prior radiotherapy for solitary plasmacytoma
• More than 28 days since other prior experimental drug or therapy
• Prior clarithromycin, DHEA, anakinra, pamidronate, or zoledronic acid allowed
• No prior lenalidomide
• No prior cytotoxic chemotherapy
• No prior corticosteroids (≥ 160 mg of dexamethasone or equivalent) for this disease

• Prior corticosteroid for nonmalignant disease allowed
• Concurrent corticosteroids allowed (≤ 20 mg/day of prednisone or equivalent)
• Concurrent palliative radiotherapy for bone pain or fracture allowed
• No other concurrent anticancer agents or treatments

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shaji K. Kumar, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MC0884

Identifier Type: OTHER

Identifier Source: secondary_id

08-002093

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2009-01201

Identifier Type: REGISTRY

Identifier Source: secondary_id

RV-MM-PI-367

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000616057

Identifier Type: -

Identifier Source: org_study_id