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Ibrutinib and PD-1 Blockade in High Risk Lymphocytic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03514017
Recruitment Status : Recruiting
First Posted : May 2, 2018
Last Update Posted : June 22, 2022
Merck Sharp & Dohme LLC
Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Brief Summary:
The purpose of this study is to evaluate the impact of sequential overlapping treatment with PD-1 monoclonal antibody (mAb), pembrolizumab/MK-1375, followed by ibrutinib on endogenous immune function in previously untreated, high-risk CLL patients. Immune function will be evaluated through various laboratory correlative tests.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: Pembrolizumab Drug: Ibrutinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Ibrutinib and PD-1 Blockade in High Risk Chronic Lymphocytic Leukemia to Improve Immune Dysfunction
Actual Study Start Date : May 31, 2019
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2023

Arm Intervention/treatment
Experimental: Pembrolizumab and Ibrutinib

Treatment with pembrolizumab and ibrutinib and follow-up period of up to 24 months.

Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2.

Ibrutinib is an inhibitor of Bruton's tyrosine kinase (BTK). Ibrutinib is a small-molecule inhibitor of BTK.

Drug: Pembrolizumab
Pembrolizumab will be administered intravenously (IV) at 200 mg every 3 weeks for 1 year and up to 2 years.
Other Name: Keytruda®

Drug: Ibrutinib
Ibrutinib will be administered orally once daily at approximately the same time each day at the dose of 420 mg daily (3 capsules of 140 mg daily).
Other Name: Imbruvica®

Primary Outcome Measures :
  1. Overall Response Rate (ORR) to the Therapeutic Intervention [ Time Frame: Up to 2 years ]
    Response categories according to The International Workshop on Chronic Lymphocytic Leukemia (IWCLL): Complete remission (CR); Complete remission with incomplete marrow recovery (CRi); Partial remission (PR); Progressive disease (PD); Stable disease (SD), defined as not meeting criteria for CR, CRi, PR or PD.

  2. Time to Response [ Time Frame: Up to 2 years ]
    Time to response to chronic lymphocytic leukemia (CLL) to the therapeutic intervention.

Secondary Outcome Measures :
  1. Restoration of Immune Response [ Time Frame: Up to 2 years ]
    Restoration of immune response as measured by: Decreased markers of T-cell exhaustion; Increased of quantitative immunoglobulin levels and subtype.

  2. Progression-free Survival (PFS) [ Time Frame: Up to 2 years ]
    Progressive disease (PD), defined as ≥ 50% rise in lymphocyte count to > 5 x10^9/L, ≥ 50% increase in lymphadenopathy, ≥ 50% increase in liver or spleen size, Richter's transformation, or new cytopenias due to CLL.

  3. Incidence of Richter's Transformation [ Time Frame: Up to 2 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Have high risk CLL
  • Have documented previously untreated CLL according to IWCLL criteria
  • Willing and able to provide written informed consent
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Demonstrate adequate organ function
  • Able to take oral medication and willing to adhere to the medication regimen

Exclusion Criteria:

  • Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
  • Meets IWCLL criteria to start therapy
  • Has had any treatment for CLL including any investigational agent, chemotherapy, mAb, anti-PD-1, anti-PDL-1, or anti-CTLA-4
  • Transformation of CLL to aggressive NHL (Richter's transformation or pro-lymphocytic leukemia)
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 90 days after the last dose of trial treatment
  • Major surgery or a wound that has not fully healed within 4 weeks of first dose
  • Additional criteria may apply

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03514017

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United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Elyse Turba    813-745-1706   
Contact: Julio Chavez, M.D.    813-745-2069   
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Merck Sharp & Dohme LLC
Janssen Scientific Affairs, LLC
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Principal Investigator: Julio Chavez, M.D. H. Lee Moffitt Cancer Center and Research Institute
Additional Information:
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Responsible Party: H. Lee Moffitt Cancer Center and Research Institute Identifier: NCT03514017    
Other Study ID Numbers: MCC-19199
First Posted: May 2, 2018    Key Record Dates
Last Update Posted: June 22, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Blood disease
White blood cells
Bone marrow disease
Additional relevant MeSH terms:
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Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antineoplastic Agents, Immunological
Antineoplastic Agents