Study of Ibrutinib in Relapsed and Refractory T-cell Lymphoma

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT02309580

Collaborator

Ohio State University (Other), Pharmacyclics LLC. (Industry), Janssen Biotech, Inc. (Industry)

Enrollment

Locations

Arm

Duration (Months)

9.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1 clinical trial, a type of research study. The purpose of this phase 1 clinical trial is to find out whether a new study drug, ibrutinib, is safe in patients with T-cell non-Hodgkin lymphoma that has either come back or not responded to treatment. In this phase 1 study, different doses of ibrutinib (560 mg and 840 mg daily) will be tested to see what effect the drug has on the patient and the disease.

Condition or Disease	Intervention/Treatment	Phase
T-cell Lymphoma Relapsed and Refractory T-cell Lymphoma	Drug: Ibrutinib	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

19 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multicenter Phase I Study of Ibrutinib in Relapsed and Refractory T-cell Lymphoma

Study Start Date :

Jan 1, 2015

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ibrutinib This will be a standard dose-escalation study to determine the MTD of ibrutinib in relapsed/refractory PTCL or CTCL. At each dose 6 patients with TCL (PTCL or CTCL) will be enrolled. The first 6 patients will be enrolled at dose level 1. Dose escalation to the next dose level will proceed after DLT assessment of all 6 patients at the end of cycle 1 (28-days).	Drug: Ibrutinib Ibrutinib will be administered once daily continuously until disease progression (confirmed by two assessments for CTCL patients only) or intolerance. The dose levels for the Phase 1 portion of the study. Either 560 mg (4 X 140 mg capsules) or 840 mg (6 X 140 mg capsules) doses will be administered. After the recommended expansion dose is established, an expansion cohort of 12 additional patients will be treated at the recommended expansion dose to further characterize the safety at that dose and to further assess preliminary efficacy

Arm

Intervention/Treatment

Experimental: Ibrutinib

This will be a standard dose-escalation study to determine the MTD of ibrutinib in relapsed/refractory PTCL or CTCL. At each dose 6 patients with TCL (PTCL or CTCL) will be enrolled. The first 6 patients will be enrolled at dose level 1. Dose escalation to the next dose level will proceed after DLT assessment of all 6 patients at the end of cycle 1 (28-days).

Drug: Ibrutinib

Ibrutinib will be administered once daily continuously until disease progression (confirmed by two assessments for CTCL patients only) or intolerance. The dose levels for the Phase 1 portion of the study. Either 560 mg (4 X 140 mg capsules) or 840 mg (6 X 140 mg capsules) doses will be administered. After the recommended expansion dose is established, an expansion cohort of 12 additional patients will be treated at the recommended expansion dose to further characterize the safety at that dose and to further assess preliminary efficacy

Outcome Measures

Primary Outcome Measures

Maximum tolerated does [1 year]
evaluate the safety and toxicities of ibrutinib in patients with relapsed/refractory Tcell lymphoma (PTCL and CTCL) as defined by CTCAE version 4.

Secondary Outcome Measures

overall response rate (ORR) [1 year]
Response and progression of disease will be evaluated in this study using the revised response criteria for malignant lymphoma with incorporation of PET/CT.33 Response in subjects with CTCL will be assessed using a specific skin scoring system with mSWAT and incorporation of measurements of extracutaneous disease.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Pathology confirmed relapsed or refractory T-cell lymphoma (PTCL and stage >IBCTCL) at treating institution
Relapse or progression after at least 1 systemic therapy
Age ≥18 years at the time of signing the informed consent form
Able to adhere to the study visit schedule and other protocol requirements
Previous systemic anti-cancer therapy must have been discontinued at least 3 weeks prior to treatment in this study. If there is progression of disease on that therapy and all adverse effects have resolved to Grade 1 or baseline, in which case 2 weeks is acceptable
Previous radiation, hormonal therapy, and surgery must have been discontinued at least 2 weeks prior to treatment in this study and adverse effects must have resolved. Lymph node or other diagnostic biopsy within 2 weeks is not considered exclusionary
Systemic corticosteroids are permissible in the following circumstances:
Short course systemic corticosteroids for disease control, improvement of performance status or non-cancer indication (≤ 7 days) must have been discontinued at least 7 days prior to study treatment.
Ongoing administration of a stable dose of corticosteroid therapy (previously received for ≥ 30 days) is permissible provided there is evidence of measurable disease and there will be no increase in steroid dose during the clinical trial
ECOG performance status of ≤ 2 at study entry
Patients who have undergone autologous stem cell transplant > 6 months prior are eligible
Patients who have undergone allogeneic stem cell transplant > 12 months, without active graft-versus-host-disease, and not on immunosuppression for prevention of graft-versus-host disease are eligible
Laboratory test results within these range:
Adequate hematologic function with screening laboratory assessment defined as:
Absolute neutrophil count >1,000 cells/mm3 (1.0 x 10^9/L)
Platelet count >75,000 cells/mm3 (75 x 10^9/L), if thrombocytopenia is due to bone marrow involvement platelet count must be ≥ 50,000 cells/mm3
Hemoglobin >8.0 g/dL
Adequate hepatic and renal function with screening laboratory assessment defined as:
Serum aspartate transaminase (AST) or alanine transaminase (ALT)

≤2.5 x upper limit of normal (ULN)

Creatinine <2.0 x ULN or Estimated Glomerular Filtration Rate GFR [Cockcroft-Gault] > 30 mL/min.
Bilirubin <1.5 x ULN [unless bilirubin rise is due to Gilbert's syndrome (as defined by >80% unconjugated hyperbilirubinemia) or of nonhepatic origin]
Females of childbearing potential (FCBP)† must have a negative serum pregnancy test and agree to use appropriate methods of birth control

Exclusion Criteria:

Patients who have a standard curative option for their lymphoid malignancy at current state of disease are excluded. For eligibility on this trial, allogeneic stem cell transplantation is not considered a standard curative option
Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc.) within 28 days of the first dose of study drug
Recent infection requiring intravenous anti-infective treatment that was completed ≤14 days before the first dose of study drug
Known bleeding diathesis (eg, von Willebrand's disease) or hemophilia
Treatment with warfarin or other Vitamin K antagonists (eg, phenprocoumon)
Any life-threatening illness, medical condition, or organ system dysfunction that, in the opinion of the investigator, could compromise the subject's safety or put the study outcomes at undue risk
Unwilling or unable to participate in all required study evaluations and procedures.
Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF)
Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment
Unable to swallow capsules, malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction
Pregnant females (Lactating females must agree not to breast feed while taking ibrutinib
Prior use of ibrutinib
Known seropositive and requiring anti-viral therapy for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) defined by PCR.
Active concurrent malignancy requiring active therapy
Known central nervous system or meningeal involvement (in the absence of symptoms investigation into central nervous system involvement is not required)
Patients who require treatment with a strong cytochrome P450 (CYP) 3A inhibitor