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Ibrutinib in Treating Patients With Relapsed or Refractory Classical Hodgkin Lymphoma

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ClinicalTrials.gov Identifier: NCT02824029
Recruitment Status : Recruiting
First Posted : July 6, 2016
Last Update Posted : March 4, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Dahlia Sano, 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.

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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 2021
Estimated Study Completion Date : September 2021

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.



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

Inclusion Criteria

  • Phase 1 Part: Patients with pathologically confirmed advanced stage B-cell NHL (Ann Arbor stage 3 or 4) for whom R-CHOP is considered appropriate therapy; newly diagnosed DLBCL, newly diagnosed low grade B cell NHL, and previously treated low grade B cell NHL patients in first relapse after a prior treatment with non-anthracycline containing chemotherapy are allowed; double hit and transformed diffuse large B cell lymphoma are allowed

    * Allowed low grade B cell lymphomas will include follicular lymphoma any grade, marginal zone lymphoma including mucosa-associated lymphoid tissue (MALT) lymphoma, indolent mantle cell lymphoma and Waldenstrom's Macroglobulinemia

  • Phase 2 Part

    • DLBCL (Arm A): Patients with pathologically confirmed newly diagnosed diffuse large B cell lymphoma (Ann Arbor stage 3 or 4) with no prior therapies; newly diagnosed double hit and transformed diffuse large B cell lymphoma a (excluding Richter's transformation from CLL) are allowed in this arm
    • Richter's transformation from CLL to DLBCL (Arm B):Patients with pathologically confirmed newly diagnosed Richter's transformation from CLL to DLBCL (all stages)
  • Patients must have measurable disease, defined as at least one lesion above and below the diaphragm or stage 4 disease that can be accurately measured in at least one dimension; lymph nodes should be considered abnormal if the long axis is > 1.5 cm and extranodal disease if the long axis is > 1.0 cm, regardless of the short axis
  • Allowed prior therapy:

    • Newly diagnosed DLBCL (phase 1 and phase 2 Arm A) and low grade B cell lymphoma (phase 1 only): No prior therapy is allowed except steroids equivalent to maximum of prednisone 60 mg once daily for maximum of ten days (or a total of dexamethasone 90 mg) prior to registration
    • Relapsed/refractory low grade B cell lymphoma (only allowed phase I): A minimum and maximum of one line of prior non-anthracycline containing therapy is allowed; prior localized radiation therapy is not considered a line

      ** Allowed low grade B cell lymphomas will include follicular lymphoma any grade, marginal zone lymphoma including MALT lymphoma, indolent mantle cell lymphoma and Waldenstrom's Macroglobulinemia

    • Newly diagnosed Richter's transformation from CLL to DLBCL (Phase 2 Arm B): No prior therapy specific to DLBCL is allowed except steroids equivalent to maximum of prednisone 60 mg once daily for maximum of ten days (or total of dexamethasone 90 mg) prior to registration; prior non-anthracycline based therapy or CLL specific therapies are allowed ** For patients who have had prior chemotherapy or immunotherapy, at least 2 weeks must have elapsed between last dose and initial dose of RCHOP-selinexor; for patients treated with radio-immunotherapy, at least 12 weeks
  • All races and ethnic groups are eligible for this trial
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 60%)
  • Life expectancy of greater than 6 months
  • Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential; acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal; for both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients with DLBCL who have received chemotherapy or immunotherapy (except one week of steroids as described above) at any time point in the past for therapy of the DLBCL; patients with low grade B cell lymphomas who have received more than one prior line of chemotherapy or any anthracycline-containing therapy in the past for their low grade B cell lymphoma; localized radiation therapy does not count as a line of therapy
  • Patients who are receiving any other investigational agents
  • Patients with known brain, spinal or cerebrospinal fluid (CSF) involvement are excluded

    * Prophylactic intrathecal therapy is allowed per institutional protocol if deemed necessary

  • History of severe allergic reactions (as determined by treating physician) attributed to the drugs being used in the study
  • Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, congestive heart failure (New York Heart Association [NYHA] class >= 3 or left ventricular ejection fraction < 45%), unstable angina pectoris, myocardial infarction within the last 3 months, clinically significant cardiac arrhythmia (i.e., ventricular tachycardia on anti-arrhythmia are excluded; 1st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] permissible), or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant and lactating women are excluded
  • Human immunodeficiency virus (HIV)-positive patients regardless of treatment are excluded; patients with evidence of active hepatitis B and hepatitis C infection with positive real time polymerase chain reaction (qPCR) are also excluded but patients with prior exposure to hepatitis B or C with negative qPCR are allowed
  • Patients with severe intolerance to glucocorticoids
  • Major surgery within 2 weeks of first dose of study drug
  • Patients who are unable to swallow tablets, patients with malabsorption syndrome, or any other gastrointestinal (GI) disease or GI dysfunction that could interfere with absorption of study treatment
  • Absolute neutrophil count (ANC) < 1500 cells/mm^3 at the time of screening
  • Platelet count < 100,000/mm^3 at the time of screening
  • Serum bilirubin > 1.5 times the upper limit of normal (ULN) (except patients with Gilbert's syndrome: total bilirubin of > 3 x ULN) at the time of screening
  • Total bilirubin of > 3 x ULN) at the time of screening
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 times ULN at the time of screening
  • Estimated creatinine clearance of < 30 mL/min, calculated using the formula of Cockcroft and Gault at the time of screening

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


Contacts
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Contact: Dahlia Sano, M.D. 800-527-6266 seymoure@karmanos.org

Locations
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United States, Michigan
University of Michigan Health System Active, not recruiting
Ann Arbor, Michigan, United States, 48109
Wayne State University/Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Dahlia Sano, M.D.    313-576-9750    seymoure@karmanos.org   
Sub-Investigator: Jay Yang, M.D.         
Sub-Investigator: Jeffrey Zonder, M.D.         
Sub-Investigator: Abhinav Deol, M.D.         
Sub-Investigator: Asif Alavi, M.D.         
Sub-Investigator: Melissa Runge-Morris, M.D.         
Sub-Investigator: Andrew Kin, M.D.         
Sub-Investigator: Dipenkumar Modi, M.D.         
Principal Investigator: Dahlia Sano, M.D.         
United States, Tennessee
University of Tennessee Recruiting
Knoxville, Tennessee, United States, 37920
Contact: Radhakrishnan Ramchandren, M.D.    734-325-3832    rramchandren@utmck.edu   
United States, Texas
M D Anderson Cancer Center Active, not recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Erlene Seymour, M.D. Barbara Ann Karmanos Cancer Institute
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Dahlia Sano, 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: March 4, 2021
Last Verified: March 2021
Additional relevant MeSH terms:
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Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases