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Ibrutinib and PD-1 Blockade in High Risk Lymphocytic Leukemia

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ClinicalTrials.gov Identifier: NCT03514017
Recruitment Status : Recruiting
First Posted : May 2, 2018
Last Update Posted : October 6, 2020
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Tracking Information
First Submitted Date  ICMJE April 20, 2018
First Posted Date  ICMJE May 2, 2018
Last Update Posted Date October 6, 2020
Actual Study Start Date  ICMJE April 10, 2019
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 20, 2018)
  • 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.
  • Time to Response [ Time Frame: Up to 2 years ]
    Time to response to chronic lymphocytic leukemia (CLL) to the therapeutic intervention.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 20, 2018)
  • 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.
  • 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.
  • Incidence of Richter's Transformation [ Time Frame: Up to 2 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ibrutinib and PD-1 Blockade in High Risk Lymphocytic Leukemia
Official Title  ICMJE Phase II Trial of Ibrutinib and PD-1 Blockade in High Risk Chronic Lymphocytic Leukemia to Improve Immune Dysfunction
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Lymphocytic Leukemia
Intervention  ICMJE
  • 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®
Study Arms  ICMJE 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.

Interventions:
  • Drug: Pembrolizumab
  • Drug: Ibrutinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 20, 2018)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03514017
Other Study ID Numbers  ICMJE MCC-19199
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party H. Lee Moffitt Cancer Center and Research Institute
Study Sponsor  ICMJE H. Lee Moffitt Cancer Center and Research Institute
Collaborators  ICMJE
  • Merck Sharp & Dohme Corp.
  • Janssen Scientific Affairs, LLC
Investigators  ICMJE
Principal Investigator: Julio Chavez, M.D. H. Lee Moffitt Cancer Center and Research Institute
PRS Account H. Lee Moffitt Cancer Center and Research Institute
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP