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Brentuximab Vedotin and BeEAM High-dose Chemotherapy in Lymphomas (BAL)

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ClinicalTrials.gov Identifier: NCT03187210
Recruitment Status : Recruiting
First Posted : June 14, 2017
Last Update Posted : September 10, 2018
Sponsor:
Collaborator:
Mundipharma Medical Company
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

Brief Summary:
The trial assess the maximum tolerated dose of a single-dose of Brentuximab Vedotin added to standard BeEAM chemotherapy (comprising Bendamustin, Etoposide, Cyclophosphamide and Melphalan) before autologous stem cell transplantation in CD30+ malignant lymphomas.

Condition or disease Intervention/treatment Phase
Lymphoma Drug: Brentuximab Vedotin Drug: BeEAM Regimen Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

The BAL trial consists in two parts:

  • single arm prospective phase I part;
  • randomized two-arm open-label prospective phase II part.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Brentuximab Vedotin and BeEAM High-dose Chemotherapy (B-BeEAM) With Autologous Stem Cell Transplantation for CD30+ Lymphomas, a Phase I/II Study
Actual Study Start Date : September 1, 2018
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Dosis finding (Phase I)
Brentuximab Vedotin at day -8 together with standard BeEAM (Bendamustine, Cytarabine, Etoposide and Melphalan) chemotherapy at days -7 to -1 followed by reinfusion of autologous stem cells at day 0
Drug: Brentuximab Vedotin
Brentuximab Vedotin at day -8 together with standard BeEAM chemotherapy at days -7 to -1 followed by ASCT on day 0

Drug: BeEAM Regimen
standard BeEAM chemotherapy at days -7 to -1 followed by ASCT on day 0

Active Comparator: Arm A (Phase II)

BeEAM Regimen:

Bendamustine intravenously once daily on days −7 and −6 at 200 mg/m2/day; Cytarabine (ARA-C) 400 mg/m2/day intravenously once daily from day −5 to day−2; Etoposide 200 mg/m2/day intravenously once daily from day −5 to day −2; and Melphalan 140 mg/m2/day intravenously once on day −1, followed by reinfusion of autologous stem cells at day 0

Drug: BeEAM Regimen
standard BeEAM chemotherapy at days -7 to -1 followed by ASCT on day 0

Experimental: Arm B (Phase II)

Brentuximab Vedotin at day -8 together with standard BeEAM chemotherapy at days -7 to -1

BeEAM Regimen:

Bendamustine intravenously once daily on days −7 and −6 at 200 mg/m2/day; Cytarabine (ARA-C) 400 mg/m2/day intravenously once daily from day −5 to day−2; etoposide 200 mg/m2/day intravenously once daily from day −5 to day −2; and Melphalan 140 mg/m2/day intravenously once on day −1, followed by reinfusion of autologous stem cells at day 0

Drug: Brentuximab Vedotin
Brentuximab Vedotin at day -8 together with standard BeEAM chemotherapy at days -7 to -1 followed by ASCT on day 0

Drug: BeEAM Regimen
standard BeEAM chemotherapy at days -7 to -1 followed by ASCT on day 0




Primary Outcome Measures :
  1. Phase 1: Dose finding [ Time Frame: 30 days ]
    to identify the maximum tolerated dose of Brentuximab Vedotin added to standard BeEAM high-dose chemotherapy testing three dose levels.

  2. Phase 2: Disease free survival at 12 months [ Time Frame: 12 months ]
    Number of Patient with disease-free survival 12 months after ASCT (DFS1) between CD30+ lymphoma patients treated with the standard BeEAM high-dose chemotherapy versus brentuximab together with BeEAM (B-BeEAM) high-dose chemotherapy. A clinically meaningful increase of the efficacy of the combination therapy (B-BeEAM) is defined in this study as an increase of the rate of disease free survival (DFS1) one year after ASCT from 70% with BeEAM alone to ≥ 90% with the combination of Brentuximab Vedotin and BeEAM.


Secondary Outcome Measures :
  1. Phase 1: disease-free survival [ Time Frame: 12 months ]
    Number of Patient with disease-free survival 12 months after ASCT

  2. Overall survival [ Time Frame: 12 Months ]
    Number of Patient alive after 12 months

  3. Adverse Events [ Time Frame: 12 months ]
    Number of Patient experiencing toxicity(Adverse events



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eligible are all CD30+ malignant lymphoma, meaning lymphoma subtypes such as Hodgkin lymphomas, angioimmunoblastic T-cell lymphomas (AITL), anaplastic ALK+ T-cell lymphomas, Sézary-syndrome, but also all other malignant CD30+ lymphoma types.
  • Patients must be in first or second remission or second chemosensitive relapse and patients must be planned to undergo subsequent consolidation with standard high-dose chemotherapy with autologous stem cell transplantation.
  • Patients must be aged 18-65 years, and must have given voluntary written informed consent.
  • Negative pregnancy test (urine or serum) within 14 days prior to registration for all women of childbearing potential. Patients of childbearing potential must implement two effective contraceptive measures (hormonal treatment p.o. or i.m., intra uterine surgical devices, or latex condoms) to avoid pregnancy from the time of signing informed consent and for additional 12 months. No pregnant or lactating patients are allowed.
  • Male patients, even if surgically sterilized, (i.e., status post vasectomy) agree to practice effective barrier contraception during the entire study period and through 12 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.
  • Absolute neutrophil count ≥ 1,500/µL unless there is known hematologic/solid tumor marrow involvement.
  • Platelet count ≥ 75,000/ µL unless there is known marrow involvement of the disease.
  • Total bilirubin must be < 1.5 x the upper limit of the normal (ULN) unless the elevation is known to be due to Gilbert syndrome.
  • ALT or AST must be < 3 x the upper limit of the normal range. AST and ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to the presence of hematologic/solid tumor in liver.
  • Serum creatinine must be < 2.0 mg/dL and/or creatinine clearance or calculated creatinine clearance > 40 mL/minute.
  • Hemoglobin must be ≥ 8g/dL.

Exclusion Criteria:

  • Patients considered to be not fit for autologous stem cell transplantation (ASCT).
  • Patients with other serious medical condition that interfere with the completion of treatment according to this protocol or that would impair tolerance to therapy or prolong hematological recovery. Patients with seropositivity for HIV or for Hepatitis B and C are not excluded from this study if they are otherwise considered fit for ASCT.
  • Symptomatic neurologic disease compromising normal activities of daily living or requiring medications. Any sensory or motor peripheral neuropathy greater than or equal to Grade 2.
  • Known history of any of the following cardiovascular conditions:

Myocardial infarction within 2 years of registration, New York Heart Association (NYHA) Class III or IV heart failure (See Appendix 5). Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.

Recent evidence (within 6 months before first dose of study drug) of a left-ventricular ejection fraction <50%.

  • Patients that have not completed any prior treatment chemotherapy and/or other investigational agents within at least 5 half-lives of last dose of that prior treatment. Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of Brentuximab Vedotin.
  • Acute uncontrolled infection.
  • Relevant co-existing disease excluding a treatment according to protocol.
  • Concurrent malignant disease with the exception of basalioma/spinalioma of the skin, early-stage cervix carcinoma, or early-stage prostate cancer. • Previous treatment for other malignancies (not listed above) must have been terminated at least 24 months before registration and no evidence of active disease must be documented since then.
  • Lack of patient cooperation to allow study treatment as outlined in this protocol.
  • Pregnant or lactating female patients.
  • Major coagulopathy or bleeding disorder.
  • Major surgery less than 30 days before start of treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03187210


Contacts
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Contact: Thomas Pabst, MD +41 31 632 84 30 thomas.pabst@insel.ch

Locations
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Switzerland
Department for Medical Oncology University Hospital/Inselspital Recruiting
Berne, Switzerland, 3010
Principal Investigator: Thomas Pabst, Prof Dr med         
Sponsors and Collaborators
University Hospital Inselspital, Berne
Mundipharma Medical Company
Investigators
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Study Chair: Thomas Pabst, MD Department of Medical Oncology, University Hospital Bern

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Responsible Party: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT03187210     History of Changes
Other Study ID Numbers: BAL-Trial
First Posted: June 14, 2017    Key Record Dates
Last Update Posted: September 10, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital Inselspital, Berne:
CD30+ Lymphoma
ASCT
Brentuximab Vedotin

Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs