Study of Ibrutinib in Relapsed and Refractory T-cell Lymphoma

NCT02309580 | Completed Phase 1 DMC

• 1 other identifier: 14-227
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

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.

Conditions

T-cell Lymphoma; Relapsed and Refractory T-cell Lymphoma

Keywords

Ibrutinib; 14-227

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated does

  evaluate the safety and toxicities of ibrutinib in patients with relapsed/refractory Tcell lymphoma (PTCL and CTCL) as defined by CTCAE version 4.

  1 year

Secondary Outcomes (1)

• overall response rate (ORR)

  1 year

Study Arms (1)

Ibrutinib

EXPERIMENTAL

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

Interventions

Ibrutinib DRUG

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

Ibrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Ohio State University: collaborator
• Pharmacyclics LLC.: collaborator
• Janssen Biotech, Inc.: collaborator

Study Sites (2)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Kumar A, Vardhana S, Moskowitz AJ, Porcu P, Dogan A, Dubovsky JA, Matasar MJ, Zhang Z, Younes A, Horwitz SM. Pilot trial of ibrutinib in patients with relapsed or refractory T-cell lymphoma. Blood Adv. 2018 Apr 24;2(8):871-876. doi: 10.1182/bloodadvances.2017011916.

  PMID: 29669753 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma, T-Cell; Recurrence

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Anita Kumar, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2014
• First Posted: December 5, 2014
• Study Start: January 1, 2015
• Primary Completion: May 8, 2023
• Study Completion: May 8, 2023
• Last Updated: May 9, 2023

Record last verified: 2023-05

Locations

US (2)