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B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin LymphomaPhase 1NCT02950220

Pembrolizumab and Ibrutinib in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

A Phase 1 study testing Ibrutinib, Laboratory Biomarker Analysis and Pembrolizumab in people with B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma and Grade 1 Follicular Lymphoma, run by Kami Maddocks at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase I/Ib trial studies the side effects and best dose of ibrutinib when given together with pembrolizumab and to see how well they work in treating patients with non-Hodgkin lymphoma that has come back or does not respond to treatment. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ibrutinib, Laboratory Biomarker Analysis and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
12 Jan 2017to 3 Jan 2019
Phase
Phase 1
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed B-cell NHL with any of the following subtypes: diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal zone lymphoma (MZL) and lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia (LL/WM), Burkitt's lymphoma (BL); patients with histological transformation to DLBCL from indolent lymphoma, primary mediastinal lymphoma and grey zone lymphoma are eligible (Part 1)
  • Patients must have received at least one prior therapy; prior autologous stem cell transplant is permitted; patients with DLBCL who have not had prior high-dose therapy (HDT)/autologous stem cell transplant (ASCT) must be ineligible for transplant; prior ibrutinib is not permitted if patients have progressed on therapy (Part 1)
  • Patients with Waldenstrom's macroglobulinemia (WM) must meet the indications for treatment per the International Workshop on Waldenstrom's Macroglobulinemia (IWWM) (Part 1)
  • Histologically confirmed B-cell NHL (Part 2):
  • Group 1: with only de novo DLBCL,
  • Group 2: with only FL of grade 1, 2 or 3a
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  • Group 3: with only MCL with t(11;14) or overexpression of cyclin D1
  • Group 4: all other NHL including MZL, LL, WM, BL, primary mediastinal B cell lymphoma (PMBCL), gray zone lymphoma (GZL) and patients with histological transformation to DLBCL from indolent lymphoma are eligible
  • Patients must have received at least one prior therapy; prior autologous stem cell transplant is permitted; patients with DLBCL who have not had prior HDT/ASCT must be ineligible for transplant; prior ibrutinib is not permitted if patients have progressed on therapy (Part 2)
  • Patients with Waldenstrom's macroglobulinemia (WM) must meet the indications for treatment per the International Workshop on Waldenstrom's Macroglobulinemia (IWWM) (Part 2)
  • Be willing and able to provide written informed consent/assent for the trial
  • Have evaluable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Absolute neutrophil count (ANC) >= 1,000/mcL
  • Platelets >= 50,000/mcL in the absence of transfusion support within 7 days of determining eligibility
  • Hemoglobin >= 8 g/dL
  • Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) OR >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
  • Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
  • Aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases
  • Albumin >= 2.5 mg/dL
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic
  • Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • 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 should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
  • Male subjects should agree to use an adequate method of 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; subjects may use topical or inhaled corticosteroids or low-dose steroids (=< 10 mg of prednisone or equivalent per day) as therapy for comorbid conditions; during study participation, subjects may receive systemic or enteric corticosteroids as needed for treatment-emergent comorbid conditions
  • Has a known history of active TB (Bacillus tuberculosis)
  • Hypersensitivity to pembrolizumab or ibrutinib 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 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; patients must be 4 weeks out from major procedures and 2 weeks out from minor procedures
  • 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) lymphoma
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Has known history of, or any evidence of active, non-infectious pneumonitis
  • Has evidence of immune- mediated hepatitis, nephritis, or thyroiditis
  • Has evidence of interstitial lung disease
  • Has evidence of colitis
  • Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years
  • Requires treatment with a strong CYP3A4 inhibitor/inducer
  • Known bleeding disorders
  • Requires therapeutic anticoagulation with warfarin or other vitamin K antagonists
  • History of stroke or intracranial hemorrhage within 6 months of the first dose of study drug
  • Has an active infection requiring intravenous 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 unable to swallow capsules or malabsorption syndrome, disease or condition significantly affecting gastrointestinal function
  • Clinically significant cardiovascular disease with uncontrolled arrhythmia, New York Association class 3 or 4 congestive heart failure, history of myocardial infarction within 6 months, or prolonged corrected QT (QTc) > 500 msec
  • 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
  • Has progressed on prior therapy with ibrutinib or other BTK inhibitors
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [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

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Phase I/Ib Study of the PD-1 Antibody Pembrolizumab in Combination With Ibrutinib in Relapsed/Refractory Non-Hodgkin's Lymphoma (NHL)

This phase I/Ib trial studies the side effects and best dose of ibrutinib when given together with pembrolizumab and to see how well they work in treating patients with non-Hodgkin lymphoma that has come back or does not respond to treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Given pembrolizumab and ibrutinib may work better in treating patients with non-Hodgkin lymphoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety and tolerability of the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory non-Hodgkin lymphoma (NHL).

II. To determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory NHL.

III. To evaluate the efficacy of the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory NHL.

SECONDARY OBJECTIVES:

  1. To determine the overall response rate (ORR), duration of response, progression-free survival and overall survival of the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory NHL.

TERTIARY OBJECTIVES:

  1. To explore the relationship between prognostic parameters including ki-67 staining, PD-1 staining and cell of origin (activated B-cell or ABC versus germinal center B-cell or GCB) with ORR to the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory NHL.

II. To determine relationship between gene mutations and resistance to therapy with the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory NHL (BTK, PLC gamma 2, PD-1).

III. To evaluate and monitor effects on B-, T-, and natural killer (NK)-cell function with the combination of ibrutinib and pembrolizumab in patients with relapsed/refractory NHL.

OUTLINE: This is a phase I, dose-escalation study of ibrutinib followed by a phase Ib study.

Patients receive ibrutinib orally (PO) daily on days 1-21 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days, and then every 3 months for 2 years and every 6 months for 3 years.

Being tested
Ibrutinib, Laboratory Biomarker Analysis, Pembrolizumab
Medical subject headings
Lymphoma, B-Cell, Lymphoma, Follicular, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Mantle-Cell, Waldenstrom Macroglobulinemia

What participants receive

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

  • IbrutinibDrug

    Also called BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT02950220
Study groupRoleWhat they receive
Arm 1ExperimentalNot described
Receives: Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

What is being measured

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

  1. Incidence of adverse events assessed using NCI CTCAE version 4

    Summarized based on severity and perceived attribution to study treatment. Will be assessed and tabulated by dose level.

    Measured: Up to 5 years

  2. MTD defined as the dose level at which no more than one of 6 patients experiences a dose-limiting toxicity assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4

    Measured: Up to 21 days

Secondary outcomes (4)

  1. Complete response rates

    Measured: Up to 5 years

  2. ORR

    Measured: Up to 5 years

  3. Overall survival

    Will be evaluated for each of the cohorts and graphically summarized using the methods of Kaplan and Meier.

    Measured: From study entry to the time of death due to any cause, assessed up to 5 years

  4. Progressive-free survival

    Will be evaluated for each of the cohorts and graphically summarized using the methods of Kaplan and Meier.

    Measured: From study entry to the time of progression and/or death, assessed up to 5 years

Timeline

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

  1. First posted1 Nov 2016 (estimated)
  2. Study start12 Jan 2017
  3. Primary completion19 Nov 2018
  4. Study completion3 Jan 2019

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02950220
Sponsor's protocol ID
OSU-16070
Other IDs
NCI-2016-01560, P30CA016058
Status last verified
Jul 2019
First submitted
28 Oct 2016
Last updated
30 Jul 2019
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 study testing Ibrutinib, Laboratory Biomarker Analysis and Pembrolizumab in people with B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma and Grade 1 Follicular Lymphoma, run by Kami Maddocks 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 25 inclusion and 32 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: finished, as of the sponsor's last update on 30 Jul 2019. 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 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.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of adverse events assessed using NCI CTCAE version 4 (time frame: Up to 5 years). The study lists 2 primary outcomes in all. 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 NCT02950220.

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 30 Jul 2019.

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