Ibrutinib and Brentuximab Vedotin in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

NCT02744612 | Completed Phase 2 Results DMC

• 2 other identifiers: 15334NCI-2016-00176
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 3

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.

Conditions

Recurrent Hodgkin Lymphoma; Refractory Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR) Rate

  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.

  Up to 8 months.

Secondary Outcomes (1)

• Overall Response Rate (ORR)

  Up to 8 months

Study Arms (2)

Arm I: Ibrutinib 420 mg PO QD + BV 1.8 mg/kg IV Q21 days

EXPERIMENTAL

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.

Drug: Brentuximab Vedotin; Drug: Ibrutinib

Arm II: Ibrutinib 560 mg PO QD + BV 1.8 mg/kg IV Q21 days

EXPERIMENTAL

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.

Drug: Brentuximab Vedotin; Drug: Ibrutinib

Interventions

Brentuximab Vedotin DRUG

Given IV

Also known as: ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN-35

Arm I: Ibrutinib 420 mg PO QD + BV 1.8 mg/kg IV Q21 days; Arm II: Ibrutinib 560 mg PO QD + BV 1.8 mg/kg IV Q21 days

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Arm I: Ibrutinib 420 mg PO QD + BV 1.8 mg/kg IV Q21 days; Arm II: Ibrutinib 560 mg PO QD + BV 1.8 mg/kg IV Q21 days

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Over 40 kg; life expectancy of greater than 3 months
• Eastern Cooperative Oncology Group (ECOG) of 0-2
• Total bilirubin within 1.5 x the upper limit of normal institutional limits; patients with elevation of unconjugated bilirubin alone, as in Gilbert's disease, are eligible
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3.0 x institutional upper limit of normal (unless demonstrated Hodgkin lymphoma involvement of the liver); estimated creatinine clearance \>= 30 ml/min (Cockcroft-Gault) and/or 24 urine analysis as needed
• Prothrombin time (PT)/international normalized ratio (INR) \< 1.5 x upper limit of normal (ULN) and partial thromboplastin time (PTT) (activated PTT \[aPTT\]) \< 1.5 x ULN

You may not qualify if:

• 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
• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
• Patients with active central nervous system (CNS) disease or history of brain metastases are excluded from study
• Patients may be on steroids prior to initiation of treatment, provided that, by cycle 1 day 1, steroids use was tapered down to less than or equal to 20 mg of prednisone
• Pregnant women are excluded from this study because of the potential teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued
• Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

NYP/Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Brentuximab Vedotin; ibrutinib

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Alex Herrera, MD
• Organization: City of Hope Medical Center

aherrera@coh.org

6263598111

Study Officials

• Alex Herrera

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2016
• First Posted: April 20, 2016
• Study Start: June 20, 2016
• Primary Completion: March 3, 2021
• Study Completion: July 30, 2024
• Last Updated: March 26, 2025
• Results First Posted: July 10, 2023

Record last verified: 2025-03

Locations

US (3)