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Ibrutinib and Brentuximab Vedotin in Treating Patients With Relapsed or Refractory 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: NCT02744612
Recruitment Status : Suspended
First Posted : April 20, 2016
Last Update Posted : May 29, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Tracking Information
First Submitted Date  ICMJE February 22, 2016
First Posted Date  ICMJE April 20, 2016
Last Update Posted Date May 29, 2020
Actual Study Start Date  ICMJE June 20, 2016
Estimated Primary Completion Date December 27, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 29, 2019)
Complete response (CR) rate; based on the Cheson criteria [ Time Frame: Up to 2 years ]
The complete response rate will be calculated as the percent of evaluable patients that have confirmed CR; exact 95% confidence intervals will be calculated for this estimate.
Original Primary Outcome Measures  ICMJE
 (submitted: April 15, 2016)
CR rate; based on the Cheson criteria [ Time Frame: Up to 2 years ]
The complete response rate will be calculated as the percent of evaluable patients that have confirmed CR; exact 95% confidence intervals will be calculated for this estimate.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 29, 2019)
  • Number of patients with treatment related adverse events (overall), scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 [ Time Frame: Up to 2 years ]
    3a. Number of patients with treatment-related adverse events (by organ system), as assessed by CTCAE version 4.03. 3b. Number of patients with treatment-related adverse events (by grade, within each organ system), as assessed by CTCAE version 4.03. 3c. Time to onset for each treatment-related adverse event, calculated as time from start of treatment to time of onset. 3d. Duration of each treatment-related adverse event, calculated as time from initial detection (start date) of adverse event to documented resolution (stop date). 3e. Association of adverse event to treatment, defined as an adverse event with an attribution of at least possibly related to the study regimen.
  • ORR: Overall Response Rate [ Time Frame: Up to 2 years ]
    The overall response rate will be calculated as the percent of evaluable patients that have confirmed complete response (CR) or partial response (PR); exact 95% confidence intervals will be calculated for this estimate.
  • Duration of overall response [ Time Frame: Up to 2 years ]
    The duration of overall response is measured from the time measurement criteria are met for CR or PR, per Cheson criteria, (whichever is first recorded) until the first date that relapsed or progressive disease is objectively documented.
  • OS: Overall Survival [ Time Frame: Duration of time from start of treatment to time of death (due to any cause), assessed up to 2 years ]
    Will be estimated using the product-limit method of Kaplan and Meier.
  • PFS: Progression-free Survival [ Time Frame: Duration of time from start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years ]
    Will be estimated using the product-limit method of Kaplan and Meier.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2016)
  • Duration of overall response [ Time Frame: Up to 2 years ]
    The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR), per Cheson criteria, (whichever is first recorded) until the first date that relapsed or progressive disease is objectively documented.
  • Number of patients with treatment-related adverse events (overall), scored using the CTCAE version 4.03 [ Time Frame: Up to 2 years ]
    3a. Number of patients with treatment-related adverse events (by organ system), as assessed by CTCAE version 4.03. 3b. Number of patients with treatment-related adverse events (by grade, within each organ system), as assessed by CTCAE version 4.03. 3c. Time to onset for each treatment-related adverse event, calculated as time from start of treatment to time of onset. 3d. Duration of each treatment-related adverse event, calculated as time from initial detection (start date) of adverse event to documented resolution (stop date). 3e. Association of adverse event to treatment, defined as an adverse event with an attribution of at least possibly related to with the study regimen.
  • ORR: Overall Response Rate [ Time Frame: Up to 2 years ]
    The overall response rate will be calculated as the percent of evaluable patients that have confirmed CR or PR; exact 95% confidence intervals will be calculated for this estimate.
  • OS: Overall Survival [ Time Frame: Duration of time from start of treatment to time of death (due to any cause), assessed up to 2 years ]
    Will be estimated using the product-limit method of Kaplan and Meier.
  • PFS: Progression-free Survival [ Time Frame: Duration of time from start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years ]
    Will be estimated using the product-limit method of Kaplan and Meier.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ibrutinib and Brentuximab Vedotin in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma
Official Title  ICMJE A Multi-Center Phase II Trial of Ibrutinib Plus Brentuximab Vedotin in Relapsed/Refractory Hodgkin Lymphoma
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Hodgkin Lymphoma
  • Refractory Hodgkin Lymphoma
Intervention  ICMJE
  • Drug: Brentuximab Vedotin
    Given IV
    Other Names:
    • 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
  • Drug: Ibrutinib
    Given PO
    Other Names:
    • BTK Inhibitor PCI-32765
    • CRA-032765
    • Imbruvica
    • PCI-32765
Study Arms  ICMJE Experimental: Treatment (Ibrutinib and Brentuximab Vedotin)
Patients receive ibrutinib PO QD on days 1-21 and brentuximab vedotin IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: Brentuximab Vedotin
  • Drug: Ibrutinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: April 15, 2016)
39
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 27, 2021
Estimated Primary Completion Date December 27, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • 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
  • The effects of brentuximab vedotin and ibrutinib on the developing fetus is unknowm; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
  • All subjects must have the ability to understand and the willingness to sign a written informed consent; they are to give 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
  • Patient must be either refractory to or relapsed after 1 line of therapy
  • Prior hematopoietic transplantation is allowed (autologous and/or allogeneic)
  • Prior brentuximab vedotin is allowed provided that patients were not refractory (defined as developing progressive disease while on treatment or progressed within 3 months of finished last dose of brentuximab vedotin)
  • Prior ibrutinib for Hodgkin lymphoma is not allowed

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
  • 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
  • Recent infection requiring systemic treatment that was completed =< 14 days before the first dose of study drug
  • Known active infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV); testing to be done only if patients suspected of having infections or exposures; 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; subjects who have an undetectable human immunodeficiency virus (HIV) viral load with CD4 >= 200 and are on highly active antiretroviral therapy (HAART) medication are allowed
  • Currently active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification
  • STUDY-SPECIFIC EXCLUSIONS:
  • Patient has hypersensitivity to brentuximab vedotin
  • Refractory to prior brentuximab vedotin (defined as developing progressive disease while on treatment or progressed within 3 month of finished last dose of brentuximab vedotin)
  • No active graft-versus-host disease (GVHD) or on immunosuppressive medication for GVHD
  • Recent infection requiring intravenous anti-infective treatment that was completed =< 14 days before the first dose of study drug
  • Unresolved toxicities from prior anticancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4.03), grade 0 or 1, or to the levels dictated in the inclusion/exclusion criteria, with the exception of alopecia
  • Baseline grade II peripheral neuropathy
  • Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
  • History of stroke or intracranial hemorrhage within 6 months prior to enrollment
  • Major surgery within 4 weeks of first dose of study drug
  • 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
  • Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 15 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02744612
Other Study ID Numbers  ICMJE 15334
NCI-2016-00176 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
15334 ( Other Identifier: City of Hope Comprehensive Cancer Center )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party City of Hope Medical Center
Study Sponsor  ICMJE City of Hope Medical Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Alex Herrera City of Hope Medical Center
PRS Account City of Hope Medical Center
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP