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Monoclonal B-Cell LymphocytosisPhase 2NCT02309515

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

A Phase 2 study testing Laboratory Biomarker Analysis, Lenalidomide and Pneumococcal 13-valent Conjugate Vaccine in people with Monoclonal B-Cell Lymphocytosis and Stage 0 Chronic Lymphocytic Leukemia, run by Mayo Clinic at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Lenalidomide and Pneumococcal 13-valent Conjugate Vaccine
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
3 sitesUnited States
Study dates
11 Jun 2015to 21 Jul 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of:
  • CLL according to the National Cancer Institute (NCI) criteria
  • Small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) criteria
  • MBL according to the consensus criteria
  • This includes previous documentation of:
  • Biopsy-proven small lymphocytic lymphoma or
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  • Diagnosis of CLL or MBL as evidenced by all of the following:
  • Clonal B-cell population in the peripheral blood with immunophenotyping consistent with CLL defined as:
  • The population of lymphocytes share both B-cell antigens (cluster of differentiation [CD]19, CD20 [typically dim expression], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc)
  • Clonality as evidenced by k (kappa) or lambda light chain expression (typically dim immunoglobulin expression) or other genetic method (e.g. immunoglobulin heavy chain variable [IGHV] analysis) NOTE: splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL
  • Patients with a peripheral blood B-cell lymphocyte count of < 5 x 10^9/L and no evidence of lymphadenopathy or organomegaly will be classified as MBL; patients with a peripheral blood B-cell lymphocyte count of < 5 x 10^9/L who have evidence of lymphadenopathy will be classified as SLL; patients with a peripheral blood B-cell lymphocyte count >= 5 x 10^9/L will be considered to have CLL
  • Before diagnosing MBL, CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescence in situ hybridization (FISH) analysis for t(11;14)(IgH/cyclin D 1 [CCND1]) on peripheral blood or tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy
  • CLL or SLL patients only (does not apply to MBL patients): Rai stage 0-1 (both CLL and SLL patients can be staged using the Rai system)
  • Patients must not previously have received the Prevnar 13 pneumococcal vaccination; NOTE: previous vaccination with Pneumovax (PCV23) is permitted but must have been at least 365 days prior to registration
  • Patients must be previously untreated and must NOT have any of the following indications for chemotherapy:
  • Evidence of progressive marrow failure as manifested by the development of or worsening anemia (=< 11 g/dL) and/or thrombocytopenia (=< 100 x 10^9/L) not due to autoimmune disease
  • Symptomatic or progressive lymphadenopathy, splenomegaly or hepatomegaly
  • One or more of the following disease-related symptoms:
  • Weight loss >= 10% within the previous 6 months
  • Extreme fatigue attributed to CLL
  • Fevers > 100.4 degree Fahrenheit (o^F) for 2 weeks without evidence of infection
  • Drenching night sweats without evidence of infection Note: 1) Prior chemotherapy or monoclonal antibody based therapy for treatment of CLL or SLL will be considered prior therapy; nutraceutical treatments with no established benefit in CLL (such as epigallocatechin gallate or EGCG, found in green tea or other herbal treatments) will not be considered "prior treatment" 2) Prior corticosteroid therapy for an indication other than CLL/SLL will not be considered "prior treatment"; previous use of corticosteroids for treatment of autoimmune complications of CLL/SLL does not constitute prior therapy for CLL/SLL
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
  • Absolute neutrophil count (ANC) >= 1000/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 11.0 g/dL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) unless due to Gilbert's disease; if total bilirubin is > 1.5 x ULN, a direct bilirubin should be performed and must be < 1.5 mg/dL for Gilbert's to be diagnosed
  • Aspartate transaminase (AST) =< 3 x ULN
  • Calculated creatinine clearance must be >= 50 ml/min using the Cockcroft-Gault formula
  • Provide informed written consent
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  • All study participants must be willing to be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS)® program, and be willing and able to comply with the requirements of the REMS® program; NOTE: Actual registration in the Revlimid REMS® program may occur after the patient is randomized since this requirement only applies to patients randomized to Arm A
  • Females of reproductive potential must be willing to adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program; NOTE: This requirement only applies to patients randomized to Arm A
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid [ASA] may use warfarin or low molecular weight heparin)
  • Willing to provide blood samples for correlative research purposes

Who cannot join

  • Palpable lymph nodes > 3 cm in maximal dimension
  • Any of the following:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Any of the following comorbid conditions:
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  • New York Heart Association classification III or IV cardiovascular disease
  • Recent myocardial infarction (=< 30 days)
  • Uncontrolled infection
  • Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
  • Other active primary malignancy requiring treatment or limiting survival to =< 2 years prior to registration
  • Any radiation therapy =< 28 days prior to registration
  • Any major surgery =< 28 days prior to registration
  • Current use of corticosteroids; EXCEPTION: low doses of steroids (=< 10 mg of prednisone or equivalent dose of other steroid) used for treatment of nonhematologic medical conditions; NOTE: previous use of corticosteroids is allowed
  • Active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment; NOTE: patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation
  • History of deep venous thromboses or pulmonary embolism =< 365 days prior to registration
  • Co-existent diffuse large B-cell lymphoma (Richter's transformation)

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

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 (MBL)

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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 killer (NK) cells.

OUTLINE: Patients are randomized 1 of 2 treatment arms.

ARM I: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-42 and pneumococcal 13-valent conjugate vaccine intramuscularly (IM) on day 15.

ARM II: Patients receive pneumococcal 13-valent conjugate vaccine IM on day 15.

After completion of study treatment, patients are followed up at day 28, and then every 6 months for up to 2 years.

Being tested
Laboratory Biomarker Analysis, Lenalidomide, Pneumococcal 13-valent Conjugate Vaccine
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • LenalidomideDrug

    Also called CC-5013, CC5013, CDC 501, Revlimid

    Given PO

  • Pneumococcal 13-valent Conjugate VaccineBiological

    Also called PCV 13, PCV13 Vaccine, Prevnar 13

    Given IM

Study groups in NCT02309515
Study groupRoleWhat they receive
Arm I (lenalidomide, pneumococcal 13-valent conjugate vaccine)ExperimentalPatients receive lenalidomide PO QD on days 1-42 and pneumococcal 13-valent conjugate vaccine IM on day 15.
Receives: Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Biological: Pneumococcal 13-valent Conjugate Vaccine
Arm II (pneumococcal 13-valent conjugate vaccine)Active comparatorPatients receive pneumococcal 13-valent conjugate vaccine IM on day 15.
Receives: Other: Laboratory Biomarker Analysis; Biological: Pneumococcal 13-valent Conjugate Vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of Participants With Successful Response

    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.

    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.

    Measured: Day 43

Secondary outcomes (3)

  1. Disease Status by Physical Exam and Complete Blood Counts

    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.

    Measured: At 6 weeks

  2. Incidence of Adverse Events Using NCI Common Terminology Criteria for Adverse Events Version 4.0

    Adverse Events were collected during treatment according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The maximum grade for each type of adverse event will be recorded for each patient. The worst grade per patient is presented below.

    Measured: Up to day 50

  3. Time to Treatment for Progressive CLL

    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.

    Measured: Time from the date of registration to the date of initiation of treatment for progressive CLL assessed up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Dec 2014 (estimated)
  2. Study start11 Jun 2015
  3. Primary completion28 Apr 2017
  4. Study completion21 Jul 2017

Why it stopped: Slow Accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02309515
Sponsor's protocol ID
MC138E
Other IDs
NCI-2014-02373, RV-CL-CLL-PI-003938, MC138E, P30CA015083
Status last verified
Jun 2020
First submitted
3 Dec 2014
Last updated
19 Jan 2021
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis, Lenalidomide and Pneumococcal 13-valent Conjugate Vaccine in people with Monoclonal B-Cell Lymphocytosis and Stage 0 Chronic Lymphocytic Leukemia, run by Mayo Clinic at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 35 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Participants With Successful Response (time frame: Day 43). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02309515.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2021.

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