Clinical Trials /

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

NCT02744612

Description:

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. Monoclonal antibodies, such as brentuximab vedotin, may interfere with the ability of cancer cells to grow and spread. Giving ibrutinib together with brentuximab vedotin may be a better treatment for Hodgkin lymphoma.

Related Conditions:
  • Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ibrutinib and Brentuximab Vedotin in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma
  • Official Title: A Multi-Center Phase II Trial of Ibrutinib Plus Brentuximab Vedotin in Relapsed/Refractory Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 15334
  • SECONDARY ID: NCI-2016-00176
  • SECONDARY ID: 15334
  • NCT ID: NCT02744612

Conditions

  • Recurrent Hodgkin Lymphoma
  • Refractory Hodgkin Lymphoma

Interventions

DrugSynonymsArms
Brentuximab VedotinADC 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-35Treatment (Ibrutinib plus Brentuximab Vedotin)
IbrutinibBTK Inhibitor PCI-32765, CRA-032765, PCI-32765Treatment (Ibrutinib plus Brentuximab Vedotin)

Purpose

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. Monoclonal antibodies, such as brentuximab vedotin, may interfere with the ability of cancer cells to grow and spread. Giving ibrutinib together with brentuximab vedotin may be a better treatment for Hodgkin lymphoma.

Detailed Description

      PRIMARY OBJECTIVES:

      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.

      TERTIARY OBJECTIVES:

      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. Courses 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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (Ibrutinib plus Brentuximab Vedotin)Experimental
  • Brentuximab Vedotin
  • Ibrutinib

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically documented or cytologically confirmed Hodgkin
             lymphoma with cluster of differentiation (CD)30 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

          -  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 radiation therapy is allowed

          -  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; breastfeeding should be discontinued

          -  Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug

          -  Recent infection requiring intravenous anti-infective treatment that was completed =<
             14 days before the first dose of study drug

          -  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; 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 (eg, 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:15 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:CR rate; based on the Cheson criteria
Time Frame:Up to 2 years
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Duration of overall response
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Number of patients with treatment-related adverse events (overall), scored using the CTCAE version 4.03
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:ORR: Overall Response Rate
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description:Will be estimated using the product-limit method of Kaplan and Meier.
Measure: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
Safety Issue:
Description:Will be estimated using the product-limit method of Kaplan and Meier.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:City of Hope Medical Center

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