search
Back to results

Ibrutinib and PD-1 Blockade in High Risk Lymphocytic Leukemia

Primary Purpose

Chronic Lymphocytic Leukemia

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pembrolizumab
Ibrutinib
Sponsored by
H. Lee Moffitt Cancer Center and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring Lymphocytic, Leukemia, CLL, Blood disease, White blood cells, Bone marrow disease, Immunotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • H. Lee Moffitt Cancer Center and Research Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pembrolizumab and Ibrutinib

Arm Description

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.

Outcomes

Primary Outcome Measures

Overall Response Rate (ORR) to the Therapeutic Intervention
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 Best Response
Time to best response to chronic lymphocytic leukemia (CLL) to the therapeutic intervention.

Secondary Outcome Measures

Progression-free Survival (PFS)
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.

Full Information

First Posted
April 20, 2018
Last Updated
September 22, 2023
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Merck Sharp & Dohme LLC, Janssen Scientific Affairs, LLC
search

1. Study Identification

Unique Protocol Identification Number
NCT03514017
Brief Title
Ibrutinib and PD-1 Blockade in High Risk Lymphocytic Leukemia
Official Title
Phase II Trial of Ibrutinib and PD-1 Blockade in High Risk Chronic Lymphocytic Leukemia to Improve Immune Dysfunction
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Terminated
Why Stopped
Funding unavailable
Study Start Date
May 31, 2019 (Actual)
Primary Completion Date
May 16, 2023 (Actual)
Study Completion Date
May 16, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Merck Sharp & Dohme LLC, Janssen Scientific Affairs, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia
Keywords
Lymphocytic, Leukemia, CLL, Blood disease, White blood cells, Bone marrow disease, Immunotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pembrolizumab and Ibrutinib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda®
Intervention Description
Pembrolizumab will be administered intravenously (IV) at 200 mg every 3 weeks for 1 year and up to 2 years.
Intervention Type
Drug
Intervention Name(s)
Ibrutinib
Other Intervention Name(s)
Imbruvica®
Intervention Description
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).
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR) to the Therapeutic Intervention
Description
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 Frame
Up to 2 years
Title
Time to Best Response
Description
Time to best response to chronic lymphocytic leukemia (CLL) to the therapeutic intervention.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
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.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julio Chavez, M.D.
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States

12. IPD Sharing Statement

Links:
URL
https://www.moffitt.org/clinical-trials-research/clinical-trials/
Description
Moffitt Cancer Center Clinical Trials website

Learn more about this trial

Ibrutinib and PD-1 Blockade in High Risk Lymphocytic Leukemia

We'll reach out to this number within 24 hrs