Ibrutinib and Pembrolizumab in Treating Patients with Relapsed or Refractory Mantle Cell Lymphoma
Hematopoietic Malignancies
Lymphoma
Non-Hodgkin Lymphoma
Unknown Primary
18 Years and older, Male and Female
17-0554 (primary)
NCI-2017-01538
Summary
This phase I/IIa trial studies the side effects of ibrutinib and pembrolizumab and how well they work in treating patients with mantle cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving ibrutinib and pembrolizumab may work better in treating patients with mantle cell lymphoma.
Objectives
PRIMARY OBJECTIVES:
I. Assess the safety of fixed dose or, as needed, de-escalated ibrutinib/pembrolizumab in patients with mantle cell lymphoma (MCL) to determine recommended phase 2 dosing of ibrutinib. (Phase I)
II. Assess complete response (CR) rate of combination ibrutinib/pembrolizumab therapy, in comparison to historical data of ibrutinib monotherapy, in patients with MCL. (Phase IIa)
SECONDARY OBJECTIVE:
I. Assess duration of response, overall response rate, and duration of stable disease, compared to historical data of single agent ibrutinib, in patients with MCL. (Phase IIa)
EXPLORATORY OBJECTIVES:
I. Assess progression-free survival rate at 1 year and overall survival at 1 year of combination ibrutinib/pembrolizumab therapy, in comparison to historical data of ibrutinib monotherapy, in patients with MCL.
II. Assess TH2:TH1 skewing and checkpoint/costimulatory molecule expression (e.g. PD-1, CTLA-4, ICOS, OX40, GITR, CD137, BTLA, LAG3, ICOS, TIM3, TIGIT) across the immune cell repertoire as well as checkpoint/costimulatory molecule ligands (e.g. PD-L1, PD-L2, CD80, CD86) of patients during the 4 week lead-in of ibrutinib and then during pembrolizumab therapy, using mass cytometry.
OUTLINE:
Patients receive ibrutinib orally (PO) once daily (QD) on days 1-21 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 3 months.
Eligibility
- Subjects must have relapsed/refractory MCL
- Be willing and able to provide written informed consent/assent for the trial
- Have measurable disease based on the Lugano classification
- 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 principal investigator (PI)
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- Absolute neutrophil count (ANC) >= 1,000 /mcL (within 28 days of treatment initiation)
- Platelets >= 25,000/mcL (within 28 days of treatment initiation)
- Hemoglobin >= 8 g/dL (within 28 days of treatment initiation)
- Serum creatinine =< 2.0 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]) >= 60 mL/min for subject with creatinine levels > 2.0 X institutional ULN (within 28 days of treatment initiation)
* Creatinine clearance should be calculated per institutional standard
- Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (within 28 days of treatment initiation)
- Aspartate aminotransferase (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 (within 28 days of treatment initiation)
- Albumin >= 2.5 mg/dL (within 28 days of treatment initiation)
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN (within 28 days of treatment initiation)
- Activated partial thromboplastin time (aPTT) =< 1.5 X ULN (within 28 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 must be willing to use an adequate method of 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 must 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
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts...
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