Clinical Trials /

Study of Brentuximab Vedotin Plus TAK228 for Relapsed/Refractory Classical Hodgkin Lymphoma, Anaplastic Large Cell Lymphoma and Other CD30+Peripheral T-Cell Lymphomas

NCT03205891

Description:

The goal of this clinical research study is to find the highest tolerable dose of TAK228 that can be given in combination with brentuximab vedotin in patients with lymphoma. The safety of this combination will also be studied. This is an investigational study. TAK228 is not FDA approved or commercially available. It is currently being used for research purposes only. Brentuximab vedotin is FDA approved and commercially available for the treatment of different types of lymphoma. The study doctor can explain how the study drugs are designed to work. Up to 18 participants will be enrolled in this study. All will take part at MD Anderson.

Related Conditions:
  • Anaplastic Large Cell Lymphoma
  • Hodgkin Lymphoma
  • Peripheral T-Cell Lymphoma
Recruiting Status:

Withdrawn

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Brentuximab Vedotin Plus TAK228 for Relapsed/Refractory Classical Hodgkin Lymphoma, Anaplastic Large Cell Lymphoma and Other CD30+Peripheral T-Cell Lymphomas
  • Official Title: An Open Label Phase I Study of Brentuximab Vedotin Plus TAK228 for Patients With Relapsed/Refractory Classical Hodgkin Lymphoma, Anaplastic Large Cell Lymphoma and Other CD30+Peripheral T-Cell Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: 2016-0854
  • NCT ID: NCT03205891

Conditions

  • Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic
  • Classical Hodgkin Lymphoma
  • Anaplastic Large Cell Lymphoma
  • CD30+ Peripheral T-cell Lymphoma

Interventions

DrugSynonymsArms
Brentuximab VedotinSGN-35, AdcetrisBrentuximab Vedotin + TAK228
TAK228TAK-228, MLN0128Brentuximab Vedotin + TAK228

Purpose

The goal of this clinical research study is to find the highest tolerable dose of TAK228 that can be given in combination with brentuximab vedotin in patients with lymphoma. The safety of this combination will also be studied.

Detailed Description

      Study Groups:

      If participant is found to be eligible to take part in this study, participant will be
      assigned to a dose level of TAK228 based on when participant joins this study. Up to 4 dose
      levels of TAK228 will be tested. About 3-6 participants will be enrolled at each dose level.
      The first group of participants will receive the lowest dose level. Each new group will
      receive a higher dose than the group before it, if no intolerable side effects were seen.
      This will continue until the highest tolerable dose of TAK228 is found.

      Participant's dose of brentuximab vedotin will stay the same. However, if the doctor thinks
      it is needed for participant's safety, it may be lowered.

      Study Drug Administration:

      Each cycle is 21 days.

      Participant will receive brentuximab vedotin by vein over about 30 minutes on Day 1 of each
      cycle.

      Participant will take TAK228 by mouth either every day or on a 5 days on/2 days off schedule
      (a "5/2 schedule," where participant takes the study drug every day for 5 days in a row and
      then does not take any TAK228 for 2 days in a row). The study doctor will tell participant
      how often to take the study drug.

      Each dose of TAK228 should be taken at about the same time each day on an empty stomach with
      8 ounces (about 1 cup) of water. Participant should fast for 2 hours before and 1 hour after
      each dose.

      Length of Study:

      Participant may receive up to 16 cycles of study drugs. Participant will no longer be able to
      take the study drugs if the disease gets worse, if intolerable side effects occur, or if
      participant is unable to follow study directions.

      Participation in this study will be over after about 2 years of follow-up (described below).

      Study Visits:

      One (1) time every week while receiving the study drugs, blood (about 1-2 tablespoons) will
      be drawn for routine tests.

      Within 3 days before the start of Cycles 2 and beyond:

        -  Participant will have a physical exam.

        -  Blood (about 1-2 tablespoons) will be drawn for routine tests and to check participant's
           blood sugar levels. If participant can become pregnant, part of this blood sample will
           be used for a pregnancy test. Participant should fast for about 8-10 hours before this
           draw.

        -  Urine will be collected for routine tests.

        -  Participant will have an EKG.

      At the end of Cycle 1:

        -  Participant will have a core needle lymph node biopsy for biomarker testing.

        -  Blood (about 1-2 tablespoons) will be drawn for biomarker testing.

      At the end of Cycle 3 and every 3 cycles after that (Cycles 6, 9, 12, and so on), participant
      will have a CT or PET/CT scan.

      At-Home Glucose Monitoring:

      Participant is required to monitor participant's glucose (sugar) levels at home during the
      first 2 months participant is taking the study drug. If the doctor thinks it is needed,
      participant may be asked to continue monitoring participant's glucose (sugar) levels at home.
      The study staff will give participant a glucose monitor (called a glucometer) and teaches
      participant how and when to use it. Participant will bring the glucometer with participant to
      each study visit so the study staff can collect the results of the testing.

      The study team will tell participant what an "abnormal" level is and when to contact the
      study doctor/study staff.

      Participant will need to return the glucometer to the study staff at the end of the study.

      End-of-Dosing Visit:

      Within 21 days after participant's last dose of study drugs:

        -  Participant will have a physical exam.

        -  Blood (about 1-2 tablespoons) will be drawn for routine tests and to check participant's
           blood sugar levels. If participant can become pregnant, part of this sample will be used
           for a pregnancy test. Participant should fast for about 8-10 hours before this draw.

        -  Urine will be collected for routine tests.

        -  Participant will have an EKG.

        -  Participant will have a PET/CT or CT scan.

      Follow-Up:

      Every 4 months for up to 2 years:

        -  Participant will have a physical exam.

        -  Blood (about 1-2 tablespoons) will be drawn for routine tests and to check participant's
           blood sugar levels. Participant should fast for about 8-10 hours before this blood draw.

        -  Participant will have a CT scan.

      If participant is found to be eligible to receive a transplant as part of participant's
      standard care, participant may receive a transplant. Participant will sign a separate consent
      explaining that procedure and its risks in more detail. If participant has a stem cell
      transplant, participant will stop having follow-up visits as part of this study.

      This is an investigational study. TAK228 is not FDA approved or commercially available. It is
      currently being used for research purposes only. Brentuximab vedotin is FDA approved and
      commercially available for the treatment of different types of lymphoma. The study doctor can
      explain how the study drugs are designed to work.

      Up to 18 participants will be enrolled in this study. All will take part at MD Anderson.
    

Trial Arms

NameTypeDescriptionInterventions
Brentuximab Vedotin + TAK228ExperimentalParticipants receive Brentuximab Vedotin by vein on Day 1 of each cycle. Participants take TAK228 by mouth either every day, or on a 5 days on/2 days off schedule. The study doctor will tell participant how often to take the study drug. Each cycle is 21 days. Participant monitors glucose (sugar) levels at home with a glucose monitor during the first 2 months participant is taking the study drug.
  • Brentuximab Vedotin
  • TAK228

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female patients 18 years or older.

          2. Patients must have a diagnosis of relapsed or refractory classical Hodgkin lymphoma OR
             anaplastic large cell lymphoma OR non-ALCL peripheral T-cell lymphoma with a
             pre-enrollment tumor biopsy positive for CD30 by immunohistochemistry at >/= 1%. All
             patients must be refractory to or not eligible for available therapies expected to
             provide clinical benefit with the exception that if a patient would meet National
             Comprehensive Cancer Center Network (NCCN) guidelines for consideration of treatment
             with brentuximab vedotin monotherapy then that patient can be enrolled to this trial
             as this is a combination trial of brentuximab vedotin plus TAK228.

          3. Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance
             status </= 2

          4. For women: Postmenopausal for at least 1 year before the screening visit, OR
             surgically sterile, OR if they are of childbearing potential, agree to practice 1
             effective methods of contraception, and 1 additional effective (barrier) method, at
             the same time, from the time of signing the informed consent through 180 days (or
             longer, as mandated by local labeling [eg, USPI, SmPC, etc.])after the last dose of
             study drug, OR agree to practice true abstinence, when this is in line with the
             preferred and usual lifestyle of the patient (Periodic abstinence [e.g, calendar,
             ovulation, symptothermal, postovulation methods] and withdrawal, spermicide only, and
             lactational amenorrhea are not acceptable methods of contraception. Female and male
             condoms should not be used together.)

          5. #4 continued: For men, even if surgically sterilized (ie, status post-vasectomy), they
             must: Agree to practice highly effective barrier contraception during the entire study
             treatment period and through 180 days after the last dose of study drug, OR agree to
             practice true abstinence, when this is in line with the preferred and usual lifestyle
             of the patient (Periodic abstinence [e.g, calendar, ovulation, symptothermal,
             postovulation methods for the female partner] and withdrawal, spermicide only, and
             lactational amenorrhea are not acceptable methods of contraception. Female and male
             condoms should not be used together.). Agree not to donate sperm during the course of
             this study or 180 days after receiving their last dose of study drug

          6. Screening clinical laboratory values as specified below: a) Bone marrow reserve
             consistent with: absolute neutrophil count (ANC) >/= 1 x 10^9/L; platelet count >/= 90
             x 10^9/L (for patients with bone marrow involvement a platelet count of >/= 75 x
             10^9/L if needed) ; hemoglobin >/= 8 g/dL without transfusion within 1 week preceding
             study drug administration b) Hepatic: total bilirubin </= 1.5 x upper limit of normal
             (ULN), transaminases (aspartate aminotransferase/serum glutamic oxaloacetic
             transaminase-AST/SGOT and alanine aminotransferase/serum glutamic pyruvic
             transaminase-ALT/SGPT) </= 2.5 x ULN (</= 5 x ULN if liver metastases are present); c)
             Renal: creatinine clearance >/=50 mL/min based either on Cockcroft-Gault estimate or
             based on urine collection (12 or 24 hour); d) Metabolic: Glycosylated hemoglobin
             (HbA1c)<7.0%, fasting serum glucose (</=130 mg/dL) and fasting triglycerides </= 300
             mg/dL;

          7. Ability to swallow oral medications.

          8. Voluntary written consent must be given before performance of any study related
             procedure not part of standard medical care, with the understanding that consent may
             be withdrawn by the patient at any time without prejudice to future medical care.

          9. Bi-dimensionally measurable disease with at least 1 lesion >/= 1.5 cm in a single
             dimension.

        Exclusion Criteria:

          1. Central nervous system (CNS) metastasis.

          2. Other clinically significant co-morbidities, such as uncontrolled pulmonary disease,
             active central nervous system disease, active infection, or any other condition that
             could compromise the patient's participation in the study.

          3. Known human immunodeficiency virus infection.

          4. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C
             infection.

          5. Any serious medical or psychiatric illness that could, in the investigator's opinion,
             potentially interfere with the completion of treatment according to this protocol.

          6. Diagnosed or treated for another malignancy within 2 years before administration of
             the first dose of study drug, or previously diagnosed with another malignancy and have
             any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma
             in situ of any type are not excluded if they have undergone complete resection.

          7. Breast feeding or pregnant.

          8. Poorly controlled diabetes mellitus defined as glycosylated hemoglobin (HbA1c) > 7%;
             patients with a history of transient glucose intolerance due to corticosteroid
             administration may be enrolled in this study if all other inclusion/exclusion criteria
             are met

          9. Treatment with strong inhibitors and/or inducers of cytochrome P450 (CYP) 3A4, CYP2C9
             or CYP2C19 within 1 week preceding the first dose of study drug

         10. Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI
             disease, or for an unknown reason that may alter the absorption of TAK228. In
             addition, patients with enteric stomata are also excluded.

         11. Treatment with any investigational products within 14 days before the first dose of
             study drug.

         12. History of any of the following within the last 6 months before administration of the
             first dose of the drug: Ischemic myocardial event, including angina requiring therapy
             and artery revascularization procedures. Ischemic cerebrovascular event, including
             transient ischemic attack and artery revascularization procedures. Requirement for
             inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia
             (including atrial flutter/fibrillation, ventricular fibrillation or ventricular
             tachycardia). Placement of a pacemaker for control of rhythm. New York Heart
             Association (NYHA) Class III or IV heart failure. Pulmonary embolism.

         13. Significant active cardiovascular or pulmonary disease including: Uncontrolled
             hypertension (i.e., systolic blood pressure >180 mm Hg, diastolic blood pressure > 95
             mm Hg). Use of anti-hypertensive agents to control hypertension before Cycle1 Day 1 is
             allowed. Pulmonary hypertension. Uncontrolled asthma or O2 saturation < 90% by
             arterial blood gas analysis or pulse oximetry on room air. Significant valvular
             disease; severe regurgitation or stenosis by imaging independent of symptom control
             with medical intervention, or history of valve replacement. Medically significant
             (symptomatic) bradycardia. History of arrhythmia requiring an implantable cardiac
             defibrillator. Baseline prolongation of the rate-corrected QT interval (QTc) (e.g.,
             repeated demonstration of QTc interval > 480 milliseconds, or history of congenital
             long QT syndrome, or torsades de pointes).

         14. Patients receiving systemic corticosteroids (either intravenous [IV] or oral steroids,
             excluding inhalers or low-dose hormone replacement therapy) within 1 week before
             administration of the first dose of study drug.

         15. Daily or chronic use of a proton pump inhibitor (PPI) and/or having taken a PPI within
             7 days before receiving the first dose of study drug.

         16. Patients who have undergone past allogeneic stem cell transplant must be 1 year from
             completion of transplant and have not active graft versus host disease.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety of Brentuximab Vedotin Administered with TAK228 in Participants with Relapsed/Refractory Classical Hodgkin Lymphoma, Anaplastic Large Cell lymphoma and Other CD30+ Peripheral T-Cell Lymphoma Assessed by Dose Limiting Toxicities
Time Frame:21 days
Safety Issue:
Description:DLT defined as a drug-related adverse event during the first cycle of treatment

Secondary Outcome Measures

Measure:Response of Brentuximab Vedotin Administered with TAK228 in Participants with Relapsed/Refractory Classical Hodgkin Lymphoma, Anaplastic Large Cell lymphoma and Other CD30+ Peripheral T-Cell Lymphoma Assessed by Dose Limiting Toxicities
Time Frame:21 days after study drug stopped
Safety Issue:
Description:Response determined according to the Lugano Classification.(Cheson, et al 2014)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Malignant neoplasms stated as primary lymphoid haematopoietic
  • Anaplastic Large Cell Lymphoma
  • Classical Hodgkin Lymphoma
  • CD30+ peripheral T-cell lymphoma
  • Brentuximab Vedotin
  • SGN-35
  • Adcetris
  • TAK228
  • TAK-228
  • MLN0128
  • Glucose Monitor
  • Glucometer

Last Updated

September 7, 2017