Pembrolizumab Alone or With Idelalisib or Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Non-Hodgkin Lymphomas

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Scottsdale/Phoenix, Arizona: 14-005666
    • Rochester, Minnesota: 14-005666
    NCT ID: NCT02332980
    Sponsor Protocol Number: MC1485

About this study

This phase II trial studies how well pembrolizumab alone or with idelalisib or ibrutinib works in treating patients with chronic lymphocytic leukemia or other low-grade B-cell non-Hodgkin lymphomas that have returned after a period of improvement or have not responded to treatment. Monoclonal antibodies can block cancer growth in different ways. Pembrolizumab may block cancer growth by blocking a cell that protects the cancer from the immune system and allowing the immune system to attack the cancer. Idelalisib and ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab alone or with idelalisib or ibrutinib may be an effective treatment in patients with chronic lymphocytic leukemia or other low-grade B-cell non-Hodgkin lymphomas.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria

  • CLL/SLL patients only
    • Diagnosis of CLL according to the National Cancer Institute (NCI) criteria or SLL according to the World Health Organization (WHO) criteria
    • This includes previous documentation of biopsy-proven small lymphocytic lymphoma or
    • Diagnosis of CLL according to NCI working group criteria as evidenced by all of the following
      • Peripheral blood B cell count of > 5 x 10^9/L consisting of small to moderate size lymphocytes
      • Immunophenotyping consistent with CLL defined as:
        • The predominant population of lymphocytes share both B-cell antigens 
        • Clonality as evidenced by kappa (κ) or lambda (λ) light chain expression  or other genetic method
        • Splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL
        • Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescent in situ hybridization (FISH) analysis  on peripheral blood or tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy
    • Patients must be previously treated with at least one prior line of therapy
    • Prior chemotherapy or biologic novel therapy or anti-cancer monoclonal antibody based therapy for treatment of CLL 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"
      • Prior oral corticosteroid therapy for an indication other than CLL will not be considered "prior treatment"
    • Previous use of corticosteroids in the combination with other therapy for treatment of autoimmune complications of CLL does constitute prior therapy for CLL
    • Have progressive disease with any one of the following characteristics based on standard criteria for treatment as defined by the NCI-Working Group (WG) 1996
    • Symptomatic CLL characterized by any one of the following
      • Weight loss ≥ 10% within the previous 6 months
      • Extreme fatigue attributed to CLL
      • Fevers ≥ 100.5*F for 2 weeks without evidence of infection
      • Drenching night sweats without evidence of infection
    • Evidence of progressive bone marrow failure with hemoglobin ≤ 11 g/dL or platelet count ≤ 100 x 10^9/L
    • Symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly
      • Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease are not sufficient for protocol therapy
  • Low Grade B-NHL patients only
    • Histologically confirmed relapsed (response to last treatment ≥ 6 months duration) or refractory (no response to last treatment or response duration < 6 months) indolent/low grade B cell NHL
      • If patient has received previous anti-PD-1 or anti-PDL-1 consult with study chair
    • Follicular lymphoma, grades 1, 2 and 3
    • Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type
    • Splenic and nodal marginal zone lymphoma
    • Lymphoplasmacytic lymphoma including Waldenstrom macroglobulinemia
    • Measurable disease (at least 1 lesion of ≥ 1.5 cm in diameter) as detected by computed tomography (CT) or the CT images of the positron emission tomography (PET)/CT 
      • Patients with Waldenstrom macroglobulinemia are not required to have measurable disease by CT or PET/CT if monoclonal protein is detectable by serum protein electrophoresis and/or immunoglobulin M (IgM) level is at least 2 times upper limit of normal
  • All patients
    • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
    • Creatinine ≤ 1.5 X upper limit of normal (ULN) OR creatinine clearance ≥ 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
    • Platelet count ≥ 25 x 10^9/L
    • Absolute neutrophil count ≥ 0.5 X 10^9/L
    • 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 ≤ upper limit of normal
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 X ULN
    • Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only
    • Provide informed written consent
    • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
    • Willing to provide bone marrow and blood samples for correlative research purposes
    • Must have failed or be unable to tolerate or refused other available Food and Drug Administration (FDA) approved effective therapies
      • Patients should not have other treatment options considered curative

 

Exclusion Criteria

  • Currently participating in or has participated in a study of an investigational agent or using an investigational device ≤ 28 days prior to registration
  • Receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy ≤ 7 days prior to registration
    • Exceptions
      • Low doses of steroids (≤ 20 mg of prednisone or equivalent dose of other steroid/day) used for treatment of non-hematologic medical conditions
        • Previous use of corticosteroids is allowed
        • After initiation of MK-3475 therapy, steroid can be used for management of potential immune mediated adverse events  for less than 8 weeks of therapy
        • Topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption) are permitted 
  • Prior anti-cancer monoclonal antibody < 28 days prior to registration or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
  • Prior chemotherapy or radiation therapy ≤ 14 days prior to registration or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to a previously administered agent
    • Subjects with ≤ grade 2 neuropathy are an exception to this criterion and may qualify for the study
    • If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Known additional malignancy that is progressing or requires active treatment
    • Exceptions
      • Basal cell carcinoma, squamous cell carcinoma, melanoma of the skin that has undergone or will undergo potentially curative therapy
      • In situ cervical cancer that has undergone or will undergo potentially curative therapy
      • Richter's transformation or Hodgkin's transformation of the CLL are permitted
  • Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease/syndrome difficult to control in the past
    • Exceptions
      • Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule
      • Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study
      • Subjects with hypothyroidism stable on hormone replacement, diabetes or Sjogren's syndrome are permitted for the study
      • Patients who have a positive Coombs test but no evidence of hemolysis are permitted for participation
      • Patients with psoriasis not requiring systemic treatment are permitted for participation
      • Conditions not expected to recur in the absence of an external trigger are permitted to enroll
  • Evidence of interstitial lung disease or active, non-infectious pneumonitis
  • Active infection requiring systemic therapy
    • When the infection is controlled, patients are permitted for this study
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Any of the following
    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Known to be human immunodeficiency virus (HIV) positive
  • Known active hepatitis B or hepatitis C.
    • Patients with a positive hepatitis B core antibody but with negative hepatitis B DNA may participate, but must have hepatitis serologies and hepatitis B DNA monitored periodically by the treating physician
      • Intravenous immunoglobulin (IVIG) can cause a false positive hepatitis B serology. If patients receiving routine IVIG have core antibody or surface antigen positivity without evidence of active viremia (negative hepatitis B DNA) they may still participate in the study, but should have hepatitis serologies and hepatitis B DNA monitored periodically by the treating physician
  • Received a live vaccine ≤ 30 days prior to registration
  • New York Heart Association classification III or IV cardiovascular disease or recent myocardial infarction or unstable angina pectoris or cardiac arrhythmia (< 30 days)
  • Active central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells that requires therapy
  • Has a clinically significant coagulopathy per investigator's assessment
  • Has received an allogeneic stem cell transplant

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Wei Ding, M.B.B.S., Ph.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Wei Ding, M.B.B.S., Ph.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015