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

March 25, 2025 updated by: Insel Gruppe AG, University Hospital Bern

Brentuximab Vedotin and BeEAM High-dose Chemotherapy (B-BeEAM) With Autologous Stem Cell Transplantation for CD30+ Lymphomas, a Phase I/II Study

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Suspended

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Background and Rationale:

CD30+ lymphomas typically comprise Hodgkin lymphomas and a variety of T-cell non-Hodgkin lymphoma (T-NHL) entities including angioimmunoblastic T-cell lymphomas (AITL), anaplastic ALK+ large-cell T-cell lymphomas (ALCL), Sézary-syndrome, peripheral T-NHL NOS and other rare malignant T-cell lymphoma types.

The prognosis of patients with Hodgkin lymphoma (HL) is excellent for the majority of these usually young patients; however, HL patients relapsing after autologous stem-cell transplantation (ASCT) have a rather poor outcome, with approximately only up to 20% of the patients surviving longer than 5 years. For those in advanced stage Hodgkin's lymphoma multiple first-line and second-line treatments, including the combination of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) - internationally, the most widely used regimen in Hodgkin's lymphoma - is expected to cure about 70-80% of patients. However, in addition to treatment failures noted for ABVD, the regimen is often associated with unpredictable bleomycin-induced lung related toxic effects that can be life-threatening. Although High Dose Chemotherapy (HDCT) with ASCT is a curative strategy for some patients with relapsing Hodgkin lymphomas, relapse or progression after ASCT is a major limitation of this procedure. For these reason, the outcome of Hodgkin lymphoma patients relapsing after ASCT is poor, and novel concepts for such patients is an unmet clinical need.

CD30+ T-NHL generally have a limited prognosis, with a minority of patients being cured after specific lymphoma treatment. The incorporation of consolidating high-dose chemotherapy with autologous stem cell transplantation for young fit patients within the first-line treatment algorithms has improved the prognosis of such patients to some extent. However, the majority of such patients still ultimately die of their disease. Again, improvement of lymphoma treatment is an urgent requirement for these patients.

Brentuximab Vedotin (BV; Adcetris®) is an antibody-drug conjugate and is licensed in Switzerland and the European Medicine Agency region for the single-agent treatment of relapsed and refractory Hodgkin lymphoma or for relapsed and refractory anaplastic T-cell lymphoma.

BeEAM high-dose chemotherapy (comprising Bendamustin, Etoposide, Cyclophosphamide and Melphalan) is the standard conditioning regimen before ASCT for lymphoma patients.

In this trial BV will be used together with BeEAM high-dose chemotherapy according to its conventional schedule in CD30+ lymphomas as conditioning regimen before ASCT.

Objective:

Phase I: The primary objective of the trial is to assess the maximum tolerated dose of a single-dose of Brentuximab Vedotin added to standard BeEAM chemotherapy before autologous stem cell transplantation in CD30+ malignant lymphomas.

Phase II: The main objective of the trial is to assess differences in disease-free survival between CD30+ lymphoma patients treated with the standard BeEAM high-dose chemotherapy versus Brentuximab Vedotin together with BeEAM (B-BeEAM) high-dose chemotherapy. We aim to demonstrate an improvement by 20% of the rate of disease-free survival 1 year after ASCT (DFS1) from 70% in patients treated with BeEAM alone to 90% in patients treated with the combination of B-BeEAM.

Study Duration:

Phase I part was planned to last from 3 to 18 months (permitting the enrolment of minimum of 6 patients). The Phase I has been stopped after the RP2D (1.8mg/kg/day) was established with enrolment of 12 patient in 24 months. The Phase II will stop after the inclusion of 42 evaluable patients.

All patients will be followed up for up to 12 months after end of treatment..

This study will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the ICH-GCP or ISO EN 14155 (as far as applicable) as well as all national legal and regulatory requirements.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Switzerland
      • Berne, Switzerland, 3010
        • Department for Medical Oncology University Hospital/Inselspital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 18-75 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 calculated creatinine clearance > 40 mL/minute (Cockcroft-Gault).
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 1.8 mg/kg 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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
30 days
Phase 2: Disease free survival at 12 months
Time Frame: 12 months
Number of patients 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.
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Phase 1: Disease-free survival
Time Frame: 12 months
Number of patients with disease-free survival 12 months after ASCT
12 months
Phase I and II: Overall survival
Time Frame: 12 months
Number of patient alive after 12 months
12 months
Phase II: Overall response rate
Time Frame: 12 months
Number of patients experiencing complete or partial remission
12 months
Phase I and II: Adverse Events
Time Frame: 12 months
Number of patient experiencing toxicity (Adverse events)
12 months
Phase I and II: Engraftment and hematologic recovery
Time Frame: 30 days
Number of days until neutrophils recovery 0.5 G/L (from day - 8)
30 days
Phase I and II: Infectious complications
Time Frame: 12 months
Number of patients experiencing infectious complications
12 months
Phase I and II: Overall response rate
Time Frame: 12 months
Number of patients experiencing complete or partial remission
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Insel Gruppe AG, University Hospital Bern

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Mundipharma Medical Company

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Thomas Pabst, MD, Department of Medical Oncology, University Hospital Bern

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 2, 2023

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 12, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 13, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 14, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 30, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 25, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BAL-Trial

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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