A Multi-Center Phase II Trial of Ibrutinib Plus Brentuximab Vedotin in Relapsed/Refractory Hodgkin Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- Ibrutinib
- Conditions
- Recurrent Hodgkin Lymphoma
- Sponsor
- City of Hope Medical Center
- Enrollment
- 39
- Locations
- 3
- Primary Endpoint
- Complete Response (CR) Rate
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This phase II trial studies how well ibrutinib and brentuximab vedotin work in treating patients with Hodgkin lymphoma that has returned (relapsed) or does not respond to treatment (refractory). Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as brentuximab vedotin, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving ibrutinib together with brentuximab vedotin may be a better treatment for Hodgkin lymphoma.
Detailed Description
PRIMARY OBJECTIVE: I. Evaluate the anti-tumor activity of the two agent combination ibrutinib and brentuximab vedotin, as assessed by complete response (CR) rate. SECONDARY OBJECTIVES: I. Assess the safety and tolerability of the two agent combination through evaluation of toxicities, including type, frequency, severity, attribution, time course and duration. II. Obtain estimates of overall response rate (ORR), response duration and survival (overall and progression-free). III. Describe outcomes of patients who ultimately undergo autologous or allogeneic hematopoietic cell transplantation following treatment with ibrutinib/brentuximab vedotin. EXPLORATORY OBJECTIVE: I. Collect deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) from lymphoma specimens and serial plasma samples for future biomarker evaluation. OUTLINE: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-21 and brentuximab vedotin intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 2 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically documented or cytologically confirmed Hodgkin lymphoma with CD30 expression
- •Patients must have absolute neutrophil count (ANC) \>= 1000/uL; neupogen can be given before and during treatment to achieve target ANC \>= 1000/uL
- •Patients must have platelets (plt) \>= 50,000/uL; platelet transfusion and packed red blood cell transfusion can also be given prior to the start of treatment and during treatment to achieve a target plt \>= 50,000/uL provided that patients have not received growth factors for at least 14 days prior to entering trial
- •Patients must have hemoglobin \>= 8.5 g/dl; platelet transfusion and packed red blood cell transfusion can also be given prior to the start of treatment and during treatment to achieve a target hemoglobin of \>= 8.5/ul provided that patients have not received growth factors for at least 14 days prior to entering trial
- •Patients must have measurable disease \> 1.5 cm evidenced by computed tomography (CT) scan of the neck/chest/abdomen (abd)/pelvis or CT/positron emission tomography (PET) scans
- •Patients must be either refractory to or relapsed after 1 line of therapy
- •Prior radiation therapy is allowed
- •Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
- •Female subject is either post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control (i.e. a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
- •Male subject agrees to use an acceptable method of contraception for the duration of the study
Exclusion Criteria
- •Less than or equal to 40 kg
- •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
- •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)
- •Patients should not have any uncontrolled illness including ongoing or active infection
- •Patients may not be receiving any other investigational agents, or concurrent biological therapy, chemotherapy, or radiation therapy
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib and brentuximab vedotin (BV)
- •Patients must not have received prior chemotherapy or radiation for =\< 3 weeks before study enrollment, or those who have not recovered from the adverse events due to agents administered more than 3 weeks earlier are excluded
- •Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
- •Significant screening electrocardiogram (ECG) abnormalities including, but not limited to, left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) \>= 470 msec; subjects with a cardiac pacemaker who have a QTc interval of \>= 470 msec may be eligible if these findings are considered not clinically significant as documented via a cardiology evaluation
Arms & Interventions
Arm II: Ibrutinib 560 mg PO QD + BV 1.8 mg/kg IV Q21 days
Patients receive ibrutinib 560 mg PO QD on days 1-21 and brentuximab vedotin 1.8 mg/kg IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Ibrutinib
Arm I: Ibrutinib 420 mg PO QD + BV 1.8 mg/kg IV Q21 days
Patients receive ibrutinib 420 mg PO QD on days 1-21 and brentuximab vedotin 1.8 mg/kg IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Brentuximab Vedotin
Arm I: Ibrutinib 420 mg PO QD + BV 1.8 mg/kg IV Q21 days
Patients receive ibrutinib 420 mg PO QD on days 1-21 and brentuximab vedotin 1.8 mg/kg IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Ibrutinib
Arm II: Ibrutinib 560 mg PO QD + BV 1.8 mg/kg IV Q21 days
Patients receive ibrutinib 560 mg PO QD on days 1-21 and brentuximab vedotin 1.8 mg/kg IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Brentuximab Vedotin
Outcomes
Primary Outcomes
Complete Response (CR) Rate
Time Frame: Up to 8 months.
Complete response is defined based on Cheson criteria \[Cheson BD, Fisher RI, Barrington SF, et al: Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification. Journal of Clinical Oncology 32:3059-3067, 2014\]. The complete response rate was calculated as the percent of evaluable patients that have confirmed CR; exact 95% confidence intervals was calculated for this estimate.
Secondary Outcomes
- Overall Response Rate (ORR)(Up to 8 months)