We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Ibrutinib in Treating Patients With Relapsed or Refractory Classical Hodgkin Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02824029
Recruitment Status : Active, not recruiting
First Posted : July 6, 2016
Last Update Posted : June 28, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Dipenkumar Modi, 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.

Condition or disease Intervention/treatment Phase
Classical Hodgkin Lymphoma Recurrent Hodgkin Lymphoma Refractory Hodgkin Lymphoma Drug: Ibrutinib Other: Laboratory Biomarker Analysis Other: Pharmacological Study Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Multicenter Single Arm Study to Evaluate the Efficacy and Safety of Single Agent Bruton's Tyrosine Kinase Inhibitor, Ibrutinib, in Patients With Relapsed Refractory Classical Hodgkin's Lymphoma
Study Start Date : June 2016
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Ibrutinib

Arm Intervention/treatment
Experimental: Treatment (ibrutinib)
Patients receive ibrutinib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Ibrutinib
Given PO
Other Names:
  • BTK Inhibitor PCI-32765
  • CRA-032765
  • PCI-32765

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies




Primary Outcome Measures :
  1. Overall response rate (ORR) defined as the proportion of participants having a complete (CR) and partial (PR) response [ Time Frame: 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 :
  1. Duration of response (DOR) [ Time Frame: 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.

  2. Progression free survival (PFS) [ Time Frame: From date of study entry to date of progression or death. ]
    Kaplan-Meier estimate of median PFS will be reported with 95% confidence intervals.

  3. Incidence of Treatment-Emergent adverse Events (safety and tolerability) [ Time Frame: 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


Other Outcome Measures:
  1. Identify which genes and immune alterations are affected by ibrutinib. [ Time Frame: From date of study entry until completion of testing up to 24 months ]
    analysis of tumor and blood samples for gene expression, mutation analysis, and immune alterations.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Patients with relapsed or refractory classical HL who have previously received autologous stem cell transplant and/or allogeneic stem cell transplant. Patients must have received prior autologous stem cell transplant at least 12 weeks (3 months) before the first dose of ibrutinib and/or allogeneic stem cell transplant must have been completed at least 6 months prior to the first dose of Ibrutinib. OR
  • Patients with relapsed or refractory HL who have failed at least 2 lines of prior therapy and are not eligible for autologous stem cell transplant due to:

    • Inability to achieve a CR or PR prior to transplant
    • Age or comorbid conditions
    • Inability to collect stem cells
  • Completion of any prior treatment with radiation, chemotherapy, biologics, and/or other investigational agents at least 4 weeks prior to the first dose of ibrutinib. Patients must have completed any prior immunotherapy (e.g., rituximab or PD-1 inhibition) or antibody drug conjugate therapy (e.g. brentuximab vedotin) at least 4 weeks prior to the first dose of ibrutinib in the absence of clear disease progression.
  • Prior treatment with at least 2 lines of therapy for HL including brentuximab vedotin. In those patients who cannot receive brentuximab vedotin, treatment with 2 prior therapeutic regimens is sufficient.
  • Fluorodeoxyglucose (FDG)-avid disease by PET and measurable disease of at least 1.5 cm in minimum dimension by CT scan with contrast, as assessed by the site radiologist.
  • Adequate hematologic function independent of transfusion and growth factor support for at least 7 days prior to screening and randomization, with the exception of PEGylated GCSF (pegfilgrastim) and darbopoeitin which require at least 14 days prior to screening and randomization defined as:

    • Absolute neutrophil count >750 cells/mm3 (0.75 x 109/L).
    • Platelet count >50,000 cells/mm3 (50 x 109/L).
    • Hemoglobin >8.0 g/dL.
  • Adequate hepatic and renal function defined as:

    • Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN).
    • Estimated Creatinine Clearance ≥30 ml/min (Cockcroft-Gault)
    • Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
  • PT/INR <1.5 x ULN and PTT (aPTT) <1.5 x ULN.
  • Men and women ≥ 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
  • Female subjects who are of non-reproductive potential (i.e., post-menopausal by history-no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry.
  • Male and female subjects who agree to use highly effective methods of birth control (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], sexual abstinence, or sterilized partner) during the period of therapy and for 90 days after the last dose of study drug
  • Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02824029


Locations
Layout table for location information
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States, 48109
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Tennessee
University of Tennessee
Knoxville, Tennessee, United States, 37920
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Erlene Seymour, M.D. Barbara Ann Karmanos Cancer Institute
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Dipenkumar Modi, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT02824029    
Other Study ID Numbers: 2016-033
NCI-2016-00879 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2016-033 ( Other Identifier: Wayne State University/Karmanos Cancer Institute )
P30CA022453 ( U.S. NIH Grant/Contract )
First Posted: July 6, 2016    Key Record Dates
Last Update Posted: June 28, 2022
Last Verified: June 2022
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases