Clinical Trial: Lenalidomide in Improving Immune Response to Vaccine Therapy in Patients With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Monoclonal B Cell Lymphocytosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Impact of Short Term Lenalidomide on Immune Response to Prevnar 13® in Individuals With Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Leukemia (SLL), and Monoclonal B Cell Lymphocytosis (

Brief Summary: This randomized phase II trial studies how well lenalidomide improves immune response to pneumococcal 13-valent conjugate vaccine in patients with chronic lymphocytic leukemia, small lymphocytic lymphoma, or monoclonal B cell lymphocytosis. Biological therapies, such as lenalidomide, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Lenalidomide may also improve the effectiveness of pneumococcal 13-valent conjugate vaccine that is used to prevent infection.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To assess the ability of a 6 week course of low dose lenalidomide to improve the proportion of patients with monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL) who develop an immune response to pneumococcal vaccination as measured by the proportion of patients with >= 4-fold rise from pre-vaccine (day 15) for >= 2 of the 3 serotypes measured at 28 days post-vaccination by opsonophagocytic activity (OPA) of antibodies from sera.

SECONDARY OBJECTIVES:

I. Evaluate disease status by physical exam and complete blood counts in patients participating in each arm of the study at the time of the 6 week assessment of immune response.

II. Evaluate time to treatment for progressive CLL for patients on each study arm.

III. Evaluate the adverse events profile in each study arm.

TERTIARY OBJECTIVES:

I. To assess the immune response to pneumococcal vaccination as measured by fold-change from pre-vaccine (day 15) to 28 days post-vaccination in OPA geometric mean titers (GMT) of antibodies from sera.

II. To assess the immune response to pneumococcal vaccination as measured by fold-change from pre-vaccine (day 15) to 28 days post-vaccination in quantitative Streptococcus pneumoniae immunoglobulin G (IgG) GMT of antibodies from sera.

III. Evaluate the effect of 6 weeks of low dose lenalidomide on global immune function including T-cell repertoire, T-cell immune synapse, serum immunoglobulin levels, and absolute numbers of T-cell and natural kill
Sponsor: Mayo Clinic

Current Primary Outcome: Rate of response to pneumococcal 13-valent conjugate vaccine defined as a four-fold rise from baseline to 28 days after immunization (day 43) for >= 2 of the 3 serotypes studied by OPA of antibodies from sera [ Time Frame: Day 43 ]

The proportion of successes will be estimated in each arm by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated in each arm based on the normal approximation. Comparison of response rates between the two treatment groups will be performed using a one-sided z-test (based on normal approximation with pooled variance of standardized test statistics) at significance level 0.16.


Original Primary Outcome: Rate of response to pneumococcal 13-valent conjugate vaccine defined as a four-fold rise from baseline to 28 days after immunization (day 43) for >= 2 of the 3 serotypes studied by OPA of antibodies from sera [ Time Frame: Day 43 ]

The proportion of successes will be estimated in each arm by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated in each arm based on the normal approximation. Comparison of response rates between the two treatment groups will be performed using a one-sided z-test (based on normal approximation with pooled variance of standardized test statistics) at significance level 0.15.


Current Secondary Outcome:

  • Disease status by physical exam and complete blood counts [ Time Frame: At 6 weeks ]
    The distribution of disease status will be evaluated in each arm and will be summarized descriptively. Patients will be classified as responders (complete clinical response, incomplete marrow recovery, partial response) vs. non-responders (stable disease, progressive disease [PD]). For MBL, patients will be classified as not PD vs PD. Differences in disease status response will be compared between the two arms using Fisher's exact test.
  • Incidence of adverse events using NCI Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 2 years ]
    Platelets and hemoglobin will be graded according to the Grading Scale for Hematologic Adverse Events in CLL studies. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed for each arm to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
  • Time to treatment for progressive CLL [ Time Frame: Time from the date of registration to the date of initiation of treatment for progressive CLL assessed up to 2 years ]
    The distribution of time to treatment will be estimated in each arm using the method of Kaplan-Meier. Time to treatment will be compared between the two arms using log-rank statistics.


Original Secondary Outcome:

  • Disease status by physical exam and complete blood counts [ Time Frame: At 6 weeks ]
    The distribution of disease status will be evaluated in each arm and will be summarized descriptively. Patients will be classified as responders (complete clinical response, incomplete marrow recovery, partial response) vs. non-responders (stable disease, progressive disease [PD]). For MBL, patients will be classified as not PD vs PD. Differences in disease status response will be compared between the two arms using Fisher's exact test.
  • Time to treatment for progressive CLL [ Time Frame: Time from the date of registration to the date of initiation of treatment for progressive CLL assessed up to 2 years ]
    The distribution of time to treatment will be estimated in each arm using the method of Kaplan-Meier. Time to treatment will be compared between the two arms using log-rank statistics.
  • Incidence of adverse events using NCI Common Terminology Criteria for Adverse Events version 4.0. Platelets and hemoglobin will be graded according to the Grading Scale for Hematologic Adverse Events in CLL studies [ Time Frame: Up to 2 years ]
    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed for each arm to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.


Information By: Mayo Clinic

Dates:
Date Received: December 3, 2014
Date Started: June 2015
Date Completion:
Last Updated: June 13, 2016
Last Verified: June 2016