Clinical Trials /

Bendamustine Plus Brentuximab Vedotin in HL and CD30+ PTCL in First Salvage Setting

NCT02499627

Description:

This is a single-arm, open-label, multicenter, phase 2 clinical trial aimed at evaluating the efficacy and safety of the combination of bendamustine and brentuximab vedotin as a first salvage therapy in patients with relapsed or refractory Hodgkin's lymphoma or PTCL. A total of 25 patients with PTCL, and 40 with Hodgkin's lymphoma are expected to be treated according to this treatment protocol.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

    <li>Brief Title: Bendamustine Plus Brentuximab Vedotin in HL and CD30+ PTCL in First Salvage Settingli><li>Official Title: A Phase II Study With Bendamustine Plus Brentuximab Vedotin in Hodgkin's Lymphoma and CD30+ Peripheral T-cell Lymphoma in First Salvage Setting: the BBV Regimen.li>

Clinical Trial IDs

    <li>ORG STUDY ID: FIL-BBVli><li>NCT ID: NCT02499627li>

Conditions

    <li>Lymphatic Diseasesli>

Interventions

<td>Brentuximab Vedotintd><td>SGN35td><td>Bendamustine + Brentuximab for 6 cyclestd><td>Bendamustinetd><td>Levacttd><td>Bendamustine + Brentuximab for 6 cyclestd>
DrugSynonymsArms

Purpose

This is a single-arm, open-label, multicenter, phase 2 clinical trial aimed at evaluating the efficacy and safety of the combination of bendamustine and brentuximab vedotin as a first salvage therapy in patients with relapsed or refractory Hodgkin's lymphoma or PTCL. A total of 25 patients with PTCL, and 40 with Hodgkin's lymphoma are expected to be treated according to this treatment protocol.

Detailed Description

      In the study, intravenous bendamustine will be administered at a dose of 90 mg/m2 on day 1
      and 2 and brentuximab will be given intravenously at a total dose of 1.8 mg/kg on day 1 of
      each 21 days-based cycle, for 6 cycles. All patients achieving a CR can be considered
      eligible to peripheral blood stem cell mobilization (to be performed with granulocytecolony
      stimulating factor alone) and may proceed to an ASCT at any time after cycle 4.
    

Trial Arms

<td>Bendamustine + Brentuximab for 6 cyclestd><td>Experimentaltd><td>Bendamustine 90 mg/m2 d1-2. Brentuximab vedotin 1.8 mg/kg d1.Every 21 days for 6 cycles.td><td>
    <li>Brentuximab Vedotinli><li>Bendamustineli>
td>
NameTypeDescriptionInterventions

Eligibility Criteria

        Inclusion criteria for patients with classical Hodgkin's lymphoma:

          1. Patients at first relapse or with primary refractory disease (i.e. patients who have
             previously received only 1 line of treatment). Patients must have completed any prior
             treatment with radiation, chemotherapy, biologics, immunotherapy and/or other
             investigational agents at least 4 weeks prior to the first BBV dose

          2. Histologically-confirmed CD30+ disease (IHC BerH2 antibody)

          3. Age from 18 to 60 years.

          4. Fluorodeoxyglucose (FDG)-avid and measurable disease (lymph nodes must have long axis
             of 1.5 cm regardless of short axis or long axis 1.1 to 1.5 and short axis > 1.0 cm) as
             documented by both PET and CT.

          5. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          6. The following required baseline laboratory data: absolute neutrophil count (ANC) ≥
             1500/&#956;L, unless known marrow involvement due to disease, platelets ≥ 75,000/&#956;L, unless
             known marrow involvement due to disease, bilirubin ≤ 1.5 x upper limit of normal (ULN)
             or ≤ 3 x ULN for patients with Gilbert's disease, serum creatinine ≤ 1.5 X ULN,
             alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 X ULN.

          7. Serum Albumin ≥ 3 g/dL.

          8. Females of childbearing potential must have a negative serum or urine β-hCG pregnancy
             test result within 7 days prior to the first dose of therapy. Females of
             non-childbearing potential are those who are postmenopausal for more than 1 year or
             who have had a bilateral tubal ligation or hysterectomy.

          9. Both females of childbearing potential and males who have partners of childbearing
             potential must agree to use an effective contraceptive method during the study and for
             at least 6 months following the last dose of study drug.

         10. Male patients, even if surgically sterilized (i.e., post vasectomy), who:

               1. Agree to practice effective barrier contraception during the entire study
                  treatment period and through 6 months after the last dose of the study drug, or

               2. Agree to completely abstain from heterosexual intercourse.

         11. Patients must provide written informed consent

        Exclusion criteria for patients with classical Hodgkin's lymphoma:

          1. Previous treatment with bendamustine or brentuximab vedotin.

          2. Prior autologous stem cell transplant.

          3. Known history of any of the following cardiovascular conditions: myocardial infarction
             within 2 years of study entry; NYHA class III or IV heart failure; cardiac
             arrhythmias; angina; any electrocardiographic evidence of acute ischemia or conduction
             system abnormalities; recent evidence (within 6 months before the first dose of study
             drug) of a left-ventricular ejection fraction < 50%.

          4. History of another primary malignancy for within 3 years of study entry (the following
             are exempt from the 3-year limit: non-melanoma skin cancer, curatively treated
             localized prostate cancer and cervical carcinoma in situ on biopsy or a squamous
             intraepithelial lesion on PAP smear).

          5. Known cerebral/meningeal disease (HL or any other etiology) or testicular involvement.

          6. Signs or symptoms of progressive multifocal leukoencephalopathy (PML).

          7. Pre-existing Peripheral Neuropathy ≥ 2.

          8. Any active systemic viral, bacterial, or fungal infection requiring treatment with
             antimicrobial therapy within 2 weeks prior to the first dose of therapy.

          9. Current therapy with other systemic anti-neoplastic or investigational agents.

         10. Therapy with corticosteroids at greater than or equal to 20 mg/day prednisone
             equivalent within 1 week prior to the first dose of therapy.

         11. Women who are pregnant or breastfeeding.

         12. Patients with a known hypersensitivity to recombinant proteins, murine proteins, or
             any excipient contained in the drug formulation of brentuximab vedotin and to
             bendamustine.

         13. Known human immunodeficiency virus (HIV) positivity.

         14. Known hepatitis B surface antigen (HBsAg) positivity or known or suspected active
             hepatitis C infection.

         15. Patients with dementia or altered mental state that would preclude the understanding
             and rendering of informed consent.

        Inclusion criteria for patients with peripheral T-cell lymphomas:

          1. Patients with refractory or relapsed PTCL regardless of the number of prior therapy
             lines. Patients must have completed any prior treatment with radiation, chemotherapy,
             biologics, immunotherapy and/or other investigational agents at least 4 weeks prior to
             the first dose of therapy.

          2. Signed written informed consent.

          3. Age from 18 to 60 years.

          4. Histologically confirmed diagnosis of PTCL, i.e. PTCL-not otherwise specified
             (PTCL-NOS), angioimmunoblastic T cell lymphoma (AITL) and transformed mycosis
             fungoides according to the World Health Organization (WHO) 2008 classification.

          5. Histologically confirmed CD30+ PTCL (IHC BerH2 antibody).

          6. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1 at study
             entry.

          7. At least one site of measurable disease in two dimensions by computed tomography. Both
             nodal and extranodal sites will be taken into consideration (lymph nodes must have
             long axis of 1.5 cm regardless of short axis or long axis 1.1 to 1.5 cm and short axis
             > 1.0 cm).

          8. Hematology values within the following limits:

               1. absolute neutrophil count (ANC) ≥ 1500/mm3 independent of growth factor support;

               2. platelets ≥ 75,000/mm3 or ≥ 50,000/mm3 if bone marrow involvement is independent
                  of transfusion support;

               3. hemoglobin level ≥ 8 g/dL.

          9. Biochemical values within the following limits:

               1. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 x upper
                  limit of normal (ULN);

               2. total bilirubin < 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome
                  or has a non-hepatic origin);

               3. serum creatinine ≤ 2 x ULN;

               4. serum albumin ≥ 3 g/dL.

         10. Women of childbearing potential must have a negative pregnancy test within 7 days of
             receiving study medication and must agree to use effective contraception, defined as:
             oral contraceptives, double barrier method or practice true abstinence from sexual
             intercourse during the study and for at least 6 months after the last dose of study
             drug.

         11. Male subjects and their female partners of childbearing potential must be willing to
             use an appropriate method of contraception or practice true abstinence from sexual
             intercourse during the study and for at least 6 months after the last dose of study
             drug.

        Exclusion criteria for patients with peripheral T-cell lymphomas:

          1. Diagnosis of cutaneous T-cell lymphoma, anaplastic large-cell lymphoma (ALCL), mycosis
             fungoides or Sézary Syndrome.

          2. Previous treatment with bendamustine or brentuximab vedotin.

          3. Prior autologous stem cell transplant.

          4. Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient
             contained in the drug formulation of brentuximab vedotin and to bendamustine.

          5. Any serious active disease or co-morbid medical condition (according to investigator's
             decision).

          6. Prior history of malignancies other than lymphoma (except for a history of a complete
             resection for basal cell or squamous cell carcinoma of the skin or carcinoma in situ
             of the cervix or breast) unless the subject has been free of the disease for ≥ 3
             years.

          7. Pre-existing peripheral neuropathy grade ≥ 2.

          8. Signs or symptoms of progressive multifocal leukoencephalopathy (PML).

          9. Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the informed consent form.

         10. Pregnant or lactating females or men or women of childbearing potential not willing to
             use an adequate method of birth control for the duration of the study or a positive
             pregnancy test on day 1 before first dose of study drug.

         11. Central nervous system disease (meningeal and/or brain involvement by lymphoma) or
             testicular involvement.

         12. History of clinically relevant liver or renal insufficiency; significant pulmonary,
             gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or
             metabolic disturbances.

         13. Known history of any of the following cardiovascular conditions: myocardial infarction
             within 2 years of study entry; NYHA class III or IV heart failure; cardiac
             arrhythmias; angina; any electrocardiographic evidence of acute ischemia or conduction
             system abnormalities; recent evidence (within 6 months before the first dose of study
             drug) of a left-ventricular ejection fraction < 50%.

         14. Active systemic, viral, bacterial, or fungal infection requiring systemic antibiotics
             within 2 weeks prior to first dose of study drug.

         15. Known human immunodeficiency virus (HIV) positivity.

         16. Known hepatitis B surface antigen (HBsAg) positivity or known or suspected active
             hepatitis C infection.

         17. Prior allogeneic stem cell transplant

         18. Patients with dementia or altered mental state that would preclude the understanding
             and rendering of informed consent.
      
<td>Maximum Eligible Age:td><td>60 Yearstd><td>Minimum Eligible Age:td><td>18 Yearstd><td>Eligible Gender:td><td>Alltd><td>Healthy Volunteers:td><td>Notd>

Primary Outcome Measures

<td>Measure:td><td>Overall objective response rate (ORR).td><td>Time Frame:td><td>1 yeartd><td>Safety Issue:td><td/><td>Description:td><td>Proportion of patients in CR or PRtd>

Secondary Outcome Measures

<td>Measure:td><td>Duration of the response (DOR)td><td>Time Frame:td><td>1 yeartd><td>Safety Issue:td><td/><td>Description:td><td>Time from documentation of tumor response to disease progressiontd>
<td>Measure:td><td>Complete remission (CR) ratetd><td>Time Frame:td><td>1 yeartd><td>Safety Issue:td><td/><td>Description:td><td>Proportion of patients in CRtd>
<td>Measure:td><td>Progression-free survival (PFS)td><td>Time Frame:td><td>1 yeartd><td>Safety Issue:td><td/><td>Description:td><td>Time from study enrollment until disease progression or deathtd>
<td>Measure:td><td>Adverse Eventstd><td>Time Frame:td><td>1 yeartd><td>Safety Issue:td><td/><td>Description:td><td>The type, incidence, severity, seriousness, of adverse events and laboratory abnormalities observed during treatment and the assessment of any potential relationship to the study drugs.td>
<td>Measure:td><td>Overall survival (OS)td><td>Time Frame:td><td>1 yeartd><td>Safety Issue:td><td/><td>Description:td><td>Time from study enrollment until death from any causetd>

Details

<td>Phase:td><td>Phase 2td><td>Primary Purpose:td><td>Interventionaltd><td>Overall Status:td><td>Recruitingtd><td>Lead Sponsor:td><td>Fondazione Italiana Linfomi ONLUStd>

Trial Keywords

    <li>Lymphomali><li>Hodgkinli><li>PTCLli><li>CD30+li>

Last Updated

<p/>