Pembrolizumab and Ibrutinib in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma
A Phase I/Ib Study of the PD-1 Antibody Pembrolizumab in Combination With Ibrutinib in Relapsed/Refractory Non-Hodgkin's Lymphoma (NHL)
3 other identifiers
interventional
2
1 country
1
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jan 2017
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 28, 2016
CompletedFirst Posted
Study publicly available on registry
November 1, 2016
CompletedStudy Start
First participant enrolled
January 12, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 19, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
January 3, 2019
CompletedJuly 30, 2019
July 1, 2019
1.9 years
October 28, 2016
July 29, 2019
Conditions
Outcome Measures
Primary Outcomes (2)
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.
Up to 5 years
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
Up to 21 days
Secondary Outcomes (4)
Complete response rates
Up to 5 years
ORR
Up to 5 years
Overall survival
From study entry to the time of death due to any cause, assessed up to 5 years
Progressive-free survival
From study entry to the time of progression and/or death, assessed up to 5 years
Other Outcomes (4)
B, T, and NK cell subtypes
Baseline up to 5 years
Change in biomarker analysis of BTK
Baseline up to 5 years
Change in biomarker analysis of PD1
Baseline up to 5 years
- +1 more other outcomes
Study Arms (1)
Arm 1
EXPERIMENTALInterventions
Eligibility Criteria
You may qualify if:
- 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
- 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
- +10 more criteria
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; 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
- 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
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Kami Maddockslead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Kami Maddocks, MD
Ohio State University Comprehensive Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
October 28, 2016
First Posted
November 1, 2016
Study Start
January 12, 2017
Primary Completion
November 19, 2018
Study Completion
January 3, 2019
Last Updated
July 30, 2019
Record last verified: 2019-07
Data Sharing
- IPD Sharing
- Will not share