Lenalidomide and Vaccine Therapy in Treating Patients With Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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RATIONALE: Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Vaccines may help the body build an effective immune response to kill cancer cells. Giving lenalidomide together with vaccine therapy may make a stronger immune response and kill more cancer cells. PURPOSE: This phase II trial is studying how well giving lenalidomide together with vaccine therapy works in treating patients with relapsed or refractory multiple myeloma.

Detailed Description
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OBJECTIVES: Primary Determine whether lenalidomide can augment the efficacy of pneumococcal polyvalent vaccine as it correlates with lenalidomide-induced antitumor efficacy in patients with relapsed or refractory multiple myeloma. Secondary Determine the antibody responses to pneumococcal serotypes in patients treated with this regimen. Determine T-cell responses to the carrier protein CRM 197 in patients treated with this regimen. Determine the ability of lenalidomide to augment in vivo immune responsiveness as measured by cutaneous delayed-type hypersensitivity (DTH) reactions to Candida and tetanus in these patients. Determine the ability of lenalidomide to prime and/or boost systemic vaccine responses in both peripheral blood lymphocytes and marrow lymphocytes in these patients. OUTLINE: Patients are assigned to 1 of 2 treatment groups. Group 1: Patients receive oral lenalidomide on days 1-21. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity. Patients receive pneumococcal polyvalent vaccine intramuscularly (IM) 14 days prior to beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine). Group 2: Patients receive lenalidomide as in group 1. Patients receive pneumococcal polyvalent vaccine IM approximately 45 days after beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine). After completion of study treatment, patients are followed at 30 days. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Official Title
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Revlimid to Augment Efficacy of Prevnar Vaccines in Patients With Relapsed or Refractory Myeloma

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Biological: pneumococcal polyvalent vaccine
* Drug: lenalidomide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of multiple myeloma (MM) meeting all of the following criteria: Relapsed or refractory disease Previously received ≥ 2 courses of antimyeloma treatment Measurable levels of myeloma paraprotein in serum (> 0.5 g/dL) or urine (> 0.2 g/24-hour urine collection) OR serum-free light-chain disease PATIENT CHARACTERISTICS: ECOG performance status 0-2 Absolute neutrophil count ≥ 1,000/mm^3 Platelet count ≥ 75,000/mm^3 Creatinine ≤ 2.5 mg/dL 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 2 methods of highly effective contraception ≥ 4 weeks before, during, and for 4 weeks after completion of study therapy No other malignancy within the past 5 years except treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast No serious medical condition, laboratory abnormality, or psychiatric illness that would preclude study treatment or put patient at unacceptable risk No known hypersensitivity to thalidomide or lenalidomide No development of erythema nodosum in the presence of a reaction characterized by a desquamating rash while taking thalidomide or similar drugs No known hypersensitivity to any component of the pneumococcal polyvalent vaccine, including diphtheria toxin or CRM 197 No known HIV positivity No infectious hepatitis type A, B, or C PRIOR CONCURRENT THERAPY: See Disease Characteristics No more than 3 prior treatment regimens for MM More than 6 months since prior lenalidomide More than 28 days since prior experimental drug or therapy More than 1 month since prior systemic antimyeloma therapy More than 1 month since prior and no concurrent systemic corticosteroids No other concurrent anticancer agents or treatments or investigational agents No concurrent thalidomide No concurrent radiotherapy No other concurrent immune therapy or immunomodulatory agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Patients receive oral lenalidomide on days 1-21. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity. Patients receive pneumococcal polyvalent vaccine intramuscularly (IM) 14 days prior to beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine). | Biological: pneumococcal polyvalent vaccine<br>* Given intramuscularly<br>Drug: lenalidomide<br>* Given orally<br>|
| Experimental: Group 2<br>Patients receive lenalidomide as in group 1. Patients receive pneumococcal polyvalent vaccine IM approximately 45 days after beginning lenalidomide and again in approximately 2 months (after the first dose of the vaccine). | Biological: pneumococcal polyvalent vaccine<br>* Given intramuscularly<br>Drug: lenalidomide<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6B Antibody Response to Prevnar Vaccine in Peripheral Blood | Serum IgG levels against the PVC serotype were measured by ELISA | basline and 8 weeks after second vaccination | 
| 14F Antibody Response to Prevnar Vaccine in Peripheral Blood | Serum IgG levels against the PVC serotype were measured by ELISA | basline and 8 weeks after second vaccination | 
| 19F Antibody Response to Prevnar Vaccine in Peripheral Blood | Serum IgG levels against the PVC serotype were measured by ELISA | basline and 8 weeks after second vaccination | 
| 23F Antibody Response to Prevnar Vaccine in Peripheral Blood | Serum IgG levels against the PVC serotype were measured by ELISA | basline and 8 weeks after second vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma