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

NCT03153202 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: GCO 17-0554
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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 \[MCL\].

Conditions

Chronic Lymphocytic Leukemia; Mantle Cell Lymphoma

Keywords

Ibrutinib; Pembrolizumab; Chronic Lymphocytic Leukemia; Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity (DLT)

  Safety of fixed dose as determined by DLT to determine recommended phase 2 dosing

  up to 3 months

Secondary Outcomes (3)

• Complete Response (CR) rate

  up to 1 year

• Progression-free Survival Rate

  up to 1 year

• Overall Survival Rate

  up to 1 year

Study Arms (2)

Participants with CLL

EXPERIMENTAL

Participants with relapsed/ refractory Chronic Lymphocytic Leukemia (CLL) or 17p- CLL

Drug: Ibrutinib; Drug: Pembrolizumab

Participants with MCL

EXPERIMENTAL

Participants with relapsed/ refractory Mantle Cell Lymphoma (MCL)

Drug: Ibrutinib; Drug: Pembrolizumab

Interventions

Ibrutinib DRUG

once daily oral intake ibrutinib

Participants with CLL; Participants with MCL

Pembrolizumab DRUG

200mg IV pembrolizumab on Day 1 of each cycle

Participants with CLL; Participants with MCL

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 1. 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.
• Female subjects of childbearing potential (Section 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the course of the study through 120 days after the last dose of study medication.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate method of contraception as outlined in Section 5.7.1- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.

You may not qualify if:

• 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.
• Has active autoimmune disease that has required systemic treatment in the past 1 year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Sponsors & Collaborators

• Joshua Brody: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell

Interventions

ibrutinib; pembrolizumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma

Study Officials

• Joshua Brody, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: This is a non-randomized trial. Patients will be allocated to appropriate cohort A-D per their disease type and time of enrollment to study.

Study Record Dates

• First Submitted: May 11, 2017
• First Posted: May 15, 2017
• Study Start: July 14, 2017
• Primary Completion: November 1, 2025
• Study Completion (Estimated): November 1, 2026
• Last Updated: November 19, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)