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Chronic Lymphocytic LeukemiaPhase 1/2NCT03153202

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

A Phase 1/2 study testing Ibrutinib and Pembrolizumab in people with Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma, run by Joshua Brody at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
Ibrutinib and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
1 siteUnited States
Study dates
14 Jul 2017to Apr 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • 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 120 days after the last dose of trial treatment.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. Patients
  • Has previously received a btk inhibitor and had progressive disease during therapy. Patients who have previously discontinued btk inhibitor therapy because of intolerance may be considered for eligibility per the assessment of the PI and treating physician if there is reason that the patient may better tolerate btk inhibitor therapy at enrollment versus previously.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., hepatitis C virus (HCV) RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

Other trials in United States

About this study

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].

Read the 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.

  1. (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.

Keywords
Ibrutinib, Pembrolizumab, Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03153202
Study groupRoleWhat they receive
Participants with CLLExperimentalParticipants with relapsed/ refractory Chronic Lymphocytic Leukemia (CLL) or 17p- CLL
Receives: Drug: Ibrutinib; Drug: Pembrolizumab
Participants with MCLExperimentalParticipants with relapsed/ refractory Mantle Cell Lymphoma (MCL)
Receives: Drug: Ibrutinib; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Limiting Toxicity (DLT)

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

    Measured: up to 3 months

Secondary outcomes (3)

  1. Complete Response (CR) rate

    Number of participants with complete response to combination ibrutinib/pembrolizumab therapy in Phase 2

    Measured: up to 1 year

  2. Progression-free Survival Rate

    Phase 2: Number of participants with progression-free disease

    Measured: up to 1 year

  3. Overall Survival Rate

    Phase 2: Number of Participants alive at 1 year of combination therapy

    Measured: up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 May 2017
  2. Study start14 Jul 2017
  3. Primary completionApr 2027 (estimated)
  4. Study completionApr 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
23 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03153202
Sponsor's protocol ID
GCO 17-0554
Status last verified
Oct 2026
First submitted
11 May 2017
Last updated
29 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Ibrutinib and Pembrolizumab in people with Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma, run by Joshua Brody at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicity (DLT) (time frame: up to 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03153202.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.

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