Classical Hodgkin LymphomaPhase 2NCT02824029
Ibrutinib in Treating Patients With Relapsed or Refractory Classical Hodgkin Lymphoma
A Phase 2 study testing Ibrutinib, Laboratory Biomarker Analysis and Pharmacological Study in people with Classical Hodgkin Lymphoma and Recurrent Hodgkin Lymphoma, run by Barbara Ann Karmanos Cancer Institute at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Classical Hodgkin Lymphoma, Recurrent Hodgkin Lymphoma, Refractory Hodgkin Lymphoma
- What is being tested?
- Ibrutinib, Laboratory Biomarker Analysis and Pharmacological Study
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 4 sitesUnited States
- Study dates
- Jun 2016to 8 Jan 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Michigan Health System
Ann Arbor, Michigan, 48109
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
M D Anderson Cancer Center
Houston, Texas, 77030
University of Tennessee
Knoxville, Tennessee, 37920
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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.
- Being tested
- Ibrutinib, Laboratory Biomarker Analysis, Pharmacological Study
- Medical subject headings
- Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called BTK Inhibitor PCI-32765, CRA-032765, PCI-32765
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (ibrutinib) | Experimental | Patients receive ibrutinib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
Overall response rate (ORR) defined as the proportion of participants having a complete (CR) and partial (PR) response. A one-sample binomial test will be used to assess ORR.
Measured: From date of study entry to date of progression or death up to 24 months
Secondary outcomes (2)
Duration of Response (DOR)
Kaplan-Meier estimate of median DOR will be reported with 95% confidence intervals.
Measured: From date of documented tumor response, CR or PR, to date of disease progression or death, up to 24 months
Progression Free Survival (PFS)
Kaplan-Meier estimate of median PFS will be reported with 95% confidence intervals.
Measured: From date of study entry to date of progression or death up to 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2016 (estimated)
- Study startJun 2016
- Primary completion12 May 2023
- Study completion8 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Classical Hodgkin LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barbara Ann Karmanos Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Dipenkumar Modi, Barbara Ann Karmanos Cancer Institute
- Investigators
- Dipenkumar Modi, M.D., Principal investigator, Barbara Ann Karmanos Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02824029
- Sponsor's protocol ID
- 2016-033
- Other IDs
- NCI-2016-00879, 2016-033, P30CA022453
- Status last verified
- Jan 2025
- First submitted
- 20 Jun 2016
- Last updated
- 17 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Muqbil I, Chaker M, Aboukameel A, Mohammad RM, Azmi AS, Ramchandren R. Pre-clinical anti-tumor activity of Bruton's Tyrosine Kinase inhibitor in Hodgkin's Lymphoma cellular and subcutaneous tumor model. Heliyon. 2019 Aug 31;5(8):e02290. doi: 10.1016/j.heliyon.2019.e02290. eCollection 2019 Aug.
PubMed 31508518
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02824029
- Acronym / sponsor ID
- 2016-033
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Barbara Ann Karmanos Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jun 2016
- Primary completion
- 12 May 2023 (actual)
- Study completion
- 8 Jan 2025 (actual)
- First posted
- 6 Jul 2016 (estimated)
- Results
- Posted 17 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (ibrutinib) | Experimental | Drug: Ibrutinib, Other: Laboratory Biomarker Analysis, Other: Pharmacological StudyPatients receive ibrutinib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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:
- 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.
Key exclusion criteria (31 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbrutinibAlso: BTK Inhibitor PCI-32765, CRA-032765, PCI-32765Given PO | Drug | Treatment (ibrutinib) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (ibrutinib) |
| Pharmacological StudyCorrelative studies | Other | Treatment (ibrutinib) |
Primary outcome
Overall Response Rate (ORR)
Time frame: From date of study entry to date of progression or death up to 24 months
Overall response rate (ORR) defined as the proportion of participants having a complete (CR) and partial (PR) response. A one-sample binomial test will be used to assess ORR.
2 secondary outcomes
Duration of Response (DOR)
Time frame: From date of documented tumor response, CR or PR, to date of disease progression or death, up to 24 months
Progression Free Survival (PFS)
Time frame: From date of study entry to date of progression or death up to 24 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31508518Muqbil I, Chaker M, Aboukameel A, Mohammad RM, Azmi AS, Ramchandren R. Pre-clinical anti-tumor activity of Bruton's Tyrosine Kinase inhibitor in Hodgkin's Lymphoma cellular and subcutaneous tumor model. Heliyon. 2019 Aug 31;5(8):e02290. doi: 10.1016/j.heliyon.2019.e02290. eCollection 2019 Aug.
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Safety and Efficacy of Pembrolizumab (MK-3475) in Children and Young Adults With Classical Hodgkin Lymphoma (MK-3475-667/KEYNOTE-667)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dipenkumar Modi, M.D. principal investigator
Barbara Ann Karmanos Cancer Institute
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ibrutinib, Laboratory Biomarker Analysis and Pharmacological Study in people with Classical Hodgkin Lymphoma and Recurrent Hodgkin Lymphoma, run by Barbara Ann Karmanos Cancer Institute at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) (time frame: From date of study entry to date of progression or death up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02824029, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2025.