Clinical trial NCT00772915: Lenalidomide With or Without Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma
Official title: A Phase II Trial of Revlimid® and "On Demand" Dexamethasone Dosing in Patients With Newly Diagnosed Symptomatic Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma and Plasma Cell Neoplasm
Keywords: stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-10-15
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Progression-free Survival (PFS) Rate at 12 Months
timeFrame: 12 months from registration
Secondary outcomes:
measure: Confirmed Response Rate
timeFrame: Up to 18 cycles from registration
measure: Overall Survival (OS)
timeFrame: Time from registration to death (up to 3 years)
measure: Progression-free Survival (PFS)
timeFrame: Time from registration to progression or death (up to 3 years)
measure: Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Event at Least Possibly Related to Treatment (Toxicity)
timeFrame: Duration on treatment (up to 18 cycles from registration)
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Shaji K. Kumar, MD
role: STUDY_CHAIR
References: