Study to Evaluate the Safety and Preliminary Efficacy of Ibrutinib and Pembrolizumab in Patients With Chronic Lymphocytic Leukemia (CLL) or Mantle Cell Lymphoma (MCL)

Joshua Brody1 site in 1 country23 target enrollmentJuly 14, 2017

ConditionsChronic Lymphocytic Leukemia Mantle Cell Lymphoma

InterventionsIbrutinib Pembrolizumab

DrugsIbrutinib Pembrolizumab

Overview

Phase: Phase 1
Intervention: Ibrutinib
Conditions: Chronic Lymphocytic Leukemia
Sponsor: Joshua Brody
Enrollment: 23
Locations: 1
Primary Endpoint: Dose Limiting Toxicity (DLT)
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to determine the most appropriate dose for the combination of ibrutinib and pembrolizumab and to see if the combination is active for the disease. The study will monitor for any side effects and if the combination of ibrutinib and pembrolizumab works in the cancers being studied.

There will be 2 experimental drugs given to the subject in this study. One experimental drug used in this study is called ibrutinib and the second is called pembrolizumab.

This is the first time that ibrutinib will be used in combination with pembrolizumab. This combination is considered experimental. Experimental means that it is still being tested to see if it is safe and effective. Ibrutinib is a new drug known as a 'Bruton's Tyrosine Kinase (BTK) inhibitor'. Ibrutinib blocks an enzyme (protein) that affects how certain types of blood cancer cells grow and survive. Blocking this enzyme is a very important mechanism in killing blood cancer cells. Ibrutinib has been approved in the United States, Israel, and the European Union for use in adult patients with mantle cell lymphoma (MCL) and adult patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy. Pembrolizumab is an antibody (a type of human protein) that is being tested to see if it will allow the body's immune system to work against tumor cells. Pembrolizumab is approved for use by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with melanoma (skin cancer) who have received prior treatments. Pembrolizumab is not FDA approved to treat patients with chronic lymphocytic leukemia [CLL] and mantle cell lymphoma [MCL].

Detailed Description

(1) Objective: a. (Phase 1) Assess the safety of fixed dose or, as needed, de-escalated ibrutinib/pembrolizumab in patients with MCL (Cohort A) and CLL (Cohort B) to determine recommended phase 2 dosing. b. (Phase 2A): Assess CR rate of combination ibrutinib/pembrolizumab therapy, in comparison to historical data of ibrutinib monotherapy, in patients with MCL (Cohort C) and CLL (Cohort D). Hypothesis: This is an open-label Phase 1/2A study, which consists of Phase 1 (Safety Assessment Cohorts) utilizing a 3+3 dose de-escalation design and Phase 2A (Expansion Cohorts) utilizing a single arm one-stage design. All patients receive a 28 day lead-in of ibrutinib and thereafter, a treatment 'cycle' is defined as a course of treatment of 21 days starting with the intravenous administration of pembrolizumab on Day 1 of each cycle along with once daily oral intake of ibrutinib on all days. 1. The combination of ibrutinib and pembrolizumab will be safe and well tolerated. 2. The combination of ibrutinib and pembrolizumab will result in higher CR rates compared to historic data of ibrutinib monotherapy in cohorts of CLL and MCL. Secondary Objectives \& Hypotheses (1) Objective: (Phase 2A): Assess duration of response, overall response rate, and duration of stable disease, compared to historical data of single agent ibrutinib, in patients with MCL (Cohort C) and CLL (Cohort D). Hypothesis: The combination of ibrutinib and pembrolizumab will increase duration of response, overall response rate and duration of stable disease when compared to historical data of single agent ibrutinib.

Registry

clinicaltrials.gov

Start Date

July 14, 2017

End Date

November 2026

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Joshua Brody

Responsible Party

Sponsor Investigator

Principal Investigator

Joshua Brody

Assistant Professor

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

Inclusion Criteria

•Be willing and able to provide written informed consent/assent for the trial.
•Be ³ 18 years of age on day of signing informed consent.c
•Have measurable disease based on:
•Lugano classification \[6\] (cohorts A,C)
•International Workshop on CLL \[7\] (cohorts B,D)
•Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day
•Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen or leukemic blood sample, only upon written agreement from the Study PI.
•Have a performance status of 0 or 1 on the ECOG Performance Scale.
•Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 14 days of treatment initiation.
•Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Exclusion Criteria

•Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
•Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
•Has a known history of active Bacillus Tuberculosis (TB)
•Hypersensitivity to ibrutinib or pembrolizumab or any of their excipients.
•Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
•Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
•Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
•Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
•Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
•Has known active central nervous system (CNS) metastases and/or lymphomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include lymphomatous meningitis which is excluded regardless of clinical stability.