Clinical Trials /

Brentuximab Vedotin and Bendamustine for the Treatment of Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma (ALCL)

NCT01657331

Description:

This is a phase 1/2 multicenter study to assess the safety and effectiveness of brentuximab vedotin and bendamustine, when given together, in patients with Hodgkin Lymphoma or Anaplastic Large Cell Lymphoma (ALCL) that has either returned or did not respond to initial treatment(s). Patients will be accrued at Columbia University Medical Center (CUMC) and at two subsites in Canada.

Related Conditions:
  • Anaplastic Large Cell Lymphoma
  • Hodgkin Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Brentuximab Vedotin</span> and <span class="go-doc-concept go-doc-intervention">Bendamustine</span> for the Treatment of <span class="go-doc-concept go-doc-disease">Hodgkin Lymphoma</span> and <span class="go-doc-concept go-doc-disease">Anaplastic Large Cell Lymphoma</span> (ALCL)

Title

  • Brief Title: Brentuximab Vedotin and Bendamustine for the Treatment of Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma (ALCL)
  • Official Title: A Phase I/II Clinical Trial of the Combination of Brentuximab Vedotin and Bendamustine in Patients With Relapsed or Refractory Hodgkin Lymphoma or Anaplastic Large Cell Lymphoma
  • Clinical Trial IDs

    NCT ID: NCT01657331

    ORG ID: AAAJ5050

    Trial Conditions

    Hodgkin Lymphoma

    Anaplastic Large Cell Lymphoma

    Trial Interventions

    Drug Synonyms Arms
    Brentuximab Vedotin Adcetris, SGN35 Brentuximab Vedotin / Bendamustine
    Bendamustine Treanda, Bendamustine HCl Brentuximab Vedotin / Bendamustine
    Neulasta pegfilgrastim Brentuximab Vedotin / Bendamustine

    Trial Purpose

    This is a phase 1/2 multicenter study to assess the safety and effectiveness of brentuximab
    vedotin and bendamustine, when given together, in patients with Hodgkin Lymphoma or
    Anaplastic Large Cell Lymphoma (ALCL) that has either returned or did not respond to initial
    treatment(s). Patients will be accrued at Columbia University Medical Center (CUMC) and at
    two subsites in Canada.

    Detailed Description

    Brentuximab vedotin will be administered as an outpatient IV infusion on day 1 of each
    21-day cycle. Bendamustine will be given as an outpatient infusion on days 1 and 2 of a
    21-day cycle. Patients may receive prophylactic pegfilgrastim on day 3 of each cycle, or
    filgrastim for 5 to 10 days, per investigator's discretion. Patients can receive a maximum
    of 6 cycles of therapy.

    Trial Arms

    Name Type Description Interventions
    Brentuximab Vedotin / Bendamustine Experimental Subjects with relapsed or refractory Hodgkin Lymphoma or Anaplastic Large Cell Lymphoma will receive Brentuximab Vedotin in combination with Bendamustine, and prophylactic Neulasta Brentuximab Vedotin, Bendamustine, Neulasta

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically confirmed relapsed or refractory HL or ALCL.

    - Documented CD30+ expression from either original diagnosis or a tumor biopsy in the
    relapsed setting.

    - For patients with HL, subjects are eligible after failure or having declined
    autologous stem cell transplant or at least two prior multi-agent chemotherapy
    regimens if they are not autologous stem cell transplant candidates. For patients
    with ALCL, subjects are eligible after failure of at least one prior multi-agent
    chemotherapy regimen and if they are not eligible for or have declined autologous
    stem cell transplant.

    - Must have received first line chemotherapy. No upper limit for the number of prior
    therapies.

    - Patients with prior autologous or allogeneic stem cell transplant are eligible as
    long as they meet all other criteria.

    - Measurable or evaluable disease, as defined in 2008 Revised Response Criteria for
    Malignant Lymphoma(33)

    - Age > or = 18 years

    - ECOG performance status 0,1 or 2

    - Patient's must have adequate organ and marrow function as defined below

    - Absolute neutrophil count > or = 1,000 (1.0 x 109/L)

    - Platelets > or = 50,000 (50 x 109/L)

    - Total Bilirubin < or = 1.5 x institutional limits unless documented Gilbert's
    syndrome (then < 2.5 x institutional upper limit)

    - AST (SGOT)/ALT (SGPT) < or = 2.0 x institutional upper limit of normal (unless
    known hepatic involvement then < 3.5 x institutional upper limit)

    - Creatinine within normal institutional limits OR creatinine clearance > or =
    50mL/min for patients with creatinine levels above institutional normal

    - If female of childbearing age, negative serum pregnancy test within 7 days prior to
    the first dose of brentuximab vedotin in this study

    - Must be willing to use contraception during the study, and for 30 days following the
    last dose of study drug.

    - Able to understand and to sign a written consent document

    Exclusion Criteria:

    - Prior treatment with brentuximab vedotin and bendamustine in combination. May have
    received prior therapy with brentuximab vedotin or bendamustine separately.

    - Received either brentuximab vedotin or bendamustine within 3 months of receiving
    their first dose of protocol based therapy.

    - If brentuximab vedotin or bendamustine was previously received, had disease
    progression during the first 3 cycles of either brentuximab vedotin or bendamustine.

    - Systemic steroids that have not been stabilized to the equivalent of < 10 mg/day of
    prednisone 7 days prior to the initiation of the trial.

    - ANY concurrent investigational agents.

    - Exposure to chemotherapy, radiotherapy, biologics or investigational agents within 3
    weeks prior enrollment in the study.

    - Known cerebral or meningeal disease.

    - Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of
    the cervix). If there is a history of prior malignancy the patients must be disease
    free and off treatment for > or = 3 years.

    - Uncontrolled intercurrent illness including but not limited to: ongoing or active
    infection, systemic congestive heart failure Class III or IV by NYHA criteria,
    unstable angina pectoris, or cardiac arrhythmia, or in patients status post
    allogeneic transplantation with uncontrolled graft versus host disease (GVHD).

    - Pre-existing neuropathy grade III or greater.

    - Pregnant or nursing.

    - Known hypersensitivity to brentuximab vedotin, bendamustine, or mannitol.

    - Known Human Immunodeficiency Virus (HIV) positive, or hepatitis A, hepatitis B or
    hepatitis C; if hepatitis Bsurface antigen positive or Bcore antibody positive must
    have normal liver function tests and be willing and able to take anti-hepatitis
    medication such as lamivudine or equivalent.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Phase 1: Maximum tolerated dose (MTD) of brentuximab vedotin and bendamustine

    Phase 1: Dose limiting toxicities (DLT) of brentuximab vedotin and bendamustine.

    Phase 2: Overall Response Rate (CR + PR) for the combination of brentuximab vedotin and bendamustine

    Secondary Outcome Measures

    Phase 1: Progression free survival (PFS) and duration of response (DOR) for all patients.

    Phase 1: Overall response rate (ORR) (complete response (CR) + partial response (PR)) for all patients

    Phase 2: Safety and tolerability of the combination of brentuximab vedotin and bendamustine

    Phase 2: Duration of response, Progression free survival and Overall Survival (OS) for the combination of brentuximab vedotin and bendamustine

    Trial Keywords

    Hodgkin Lymphoma

    Hodgkin Disease

    Hodgkin's Disease

    Anaplastic Large Cell Lymphoma

    ALCL

    SGN+Benda

    Bendamustine

    Brentuximab Vedotin