Clinical trial NCT00445484: Lenalidomide and Vaccine Therapy in Treating Patients With Relapsed or Refractory Multiple Myeloma
Official title: Revlimid to Augment Efficacy of Prevnar Vaccines in Patients With Relapsed or Refractory Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma and Plasma Cell Neoplasm
Keywords: stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-03-09
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 6B Antibody Response to Prevnar Vaccine in Peripheral Blood
timeFrame: basline and 8 weeks after second vaccination
measure: 14F Antibody Response to Prevnar Vaccine in Peripheral Blood
timeFrame: basline and 8 weeks after second vaccination
measure: 19F Antibody Response to Prevnar Vaccine in Peripheral Blood
timeFrame: basline and 8 weeks after second vaccination
measure: 23F Antibody Response to Prevnar Vaccine in Peripheral Blood
timeFrame: basline and 8 weeks after second vaccination
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Ivan Borrello, MD
role: STUDY_CHAIR
References:
citation: Noonan K, Rudraraju L, Ferguson A, Emerling A, Pasetti MF, Huff CA, Borrello I. Lenalidomide-induced immunomodulation in multiple myeloma: impact on vaccines and antitumor responses. Clin Cancer Res. 2012 Mar 1;18(5):1426-34. doi: 10.1158/1078-0432.CCR-11-1221. Epub 2012 Jan 12.