Ibrutinib in Treating Patients With Relapsed or Refractory Classical Hodgkin Lymphoma

Phase 2

Active, not recruiting

• Conditions: Classical Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma
• Interventions: Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

• Registration Number: NCT02824029
• Lead Sponsor: Barbara Ann Karmanos Cancer Institute

Brief Summary

This phase II trial evaluates how effective 560 mg of ibrutinib taken by mouth daily is in the treatment of classical Hodgkin lymphoma which recurs or does not respond to initial treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth, by altering the environment around the tumor or by affecting the immune system.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the antitumor efficacy of single agent ibrutinib as measured by the overall response rate in patients with relapsed/refractory Hodgkin's lymphoma who have relapsed or not responded to chemotherapy, immunotherapy and/or radiation.

SECONDARY OBJECTIVES:

I. To assess duration of tumor control including duration of response (DOR) II. To assess progression free survival (PFS). III. To assess the safety and tolerability of 560mg of ibrutinib in Hodgkin lymphoma (HL) patients.

TERTIARY OBJECTIVES:

I. To assess the mechanism(s) by which ibrutinib may be active in patients with classical Hodgkin lymphoma (cHL) by the correlation of potential biomarkers with clinical outcomes.

OUTLINE:

Patients receive ibrutinib orally (PO) once daily (QD). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days then every 9 weeks for 1 year.

Study Timeline

• Study Start: 2016-06
• Study First Submitted: 2016-06-20
• Study First Submitted QC: 2016-06-30
• Study First Posted: 2016-07-06
• Primary Completion: 2023-05-12
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-12
• Last Update Posted: 2023-09-14
• Study Completion: 2024-08-18

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

Not provided

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Exclusion Criteria

• Prior allogeneic Stem cell transplant within 6 months.

• Active GVHD or concurrent treatment with immunosuppressive medications as prophylaxis for GVHD

• Previous therapy with BTK inhibition

• Known cerebral/meningeal disease

• Nodular lymphocyte predominant Hodgkin's Lymphoma subtype

• Concurrent therapy with other systemic anti-neoplastic or investigational agents

• Patients with a known hypersensitivity to any excipient contained in the drug formulation

• History of other malignancies, except:

  • Malignancy treated with curative intent and with no known active disease present for

    ≥3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.

  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.

  • Adequately treated carcinoma in situ without evidence of disease.

• Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration [>14 days] of >20 mg/day of prednisone) within 28 days of the first dose of study drug.

• Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug

• Recent infection requiring systemic treatment that was completed ≤14 days before the first dose of study drug.

• Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4), grade ≤1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia.

• Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia.

• History of stroke or intracranial hemorrhage within 6 months prior to enrollment.

• Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.

• Any uncontrolled active systemic infection

• Major surgery within 4 weeks of first dose of study drug.

• Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.

• 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 randomization

• Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.

• Concomitant use of warfarin or other Vitamin K antagonists.

• Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor

• Currently active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification

• Lactating or pregnant

• 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) and authorization to use protected health information (in accordance with national and local subject privacy regulations).

Potential subjects must be willing and able to adhere to the following prohibitions and restrictions during the course of the study to be eligible for participation. During the study, subjects should avoid consuming food and beverages containing grapefruit or Seville oranges as these contain certain ingredients that inhibit CYP3A4/5 enzymes.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (ibrutinib)	Laboratory Biomarker Analysis	Patients receive ibrutinib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Treatment (ibrutinib)	Pharmacological Study	Patients receive ibrutinib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Treatment (ibrutinib)	Ibrutinib	Patients receive ibrutinib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Overall response rate (ORR) defined as the proportion of participants having a complete (CR) and partial (PR) response	From date of study entry to date of progression or death up to 24 months	A one-sample binomial test will be used to assess ORR.

Secondary Outcome Measures

Name	Time	Method
Progression free survival (PFS)	From date of study entry to date of progression or death up to 24 months.	Kaplan-Meier estimate of median PFS will be reported with 95% confidence intervals.
Duration of response (DOR)	From date of documented tumor response, CR or PR, to date of disease progression,up to 24 months	DOR will be reported as median and range.
Incidence of Treatment-Emergent adverse Events (safety and tolerability)	From date of study entry to date of progression or death up to 24 months.	Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0

Trial Locations

Locations (4)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

University of Tennessee; 🇺🇸 Knoxville, Tennessee, United States

Wayne State University/Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

University of Michigan Health System; 🇺🇸 Ann Arbor, Michigan, United States