Brentuximab Vedotin and BeEAM High-dose Chemotherapy in Lymphomas

NCT03187210 | Suspended Phase 1

• 1 other identifier: BAL-Trial
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Lymphoma

Keywords

CD30+ Lymphoma; ASCT; Brentuximab Vedotin

Outcome Measures

Primary Outcomes (2)

• Phase 1: Dose finding

  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

  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 Outcomes (7)

• Phase 1: Disease-free survival

  12 months

• Phase I and II: Overall survival

  12 months

• Phase II: Overall response rate

  12 months

• Phase I and II: Adverse Events

  12 months

• Phase I and II: Engraftment and hematologic recovery

  30 days

Study Arms (3)

Dosis finding (Phase I)

EXPERIMENTAL

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; Drug: BeEAM Regimen

Arm A (Phase II)

ACTIVE COMPARATOR

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

Arm B (Phase II)

EXPERIMENTAL

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; Drug: BeEAM Regimen

Interventions

Brentuximab Vedotin DRUG

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

Arm B (Phase II); Dosis finding (Phase I)

BeEAM Regimen DRUG

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

Arm A (Phase II); Arm B (Phase II); Dosis finding (Phase I)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Mundipharma Medical Company: collaborator

Study Sites (1)

Department for Medical Oncology University Hospital/Inselspital

Bern, 3010, Switzerland

Location

Related Publications (1)

• Rausch C, Bacher U, Rabaglio M, Vorburger C, Klingenberg A, Banz Y, Daskalakis M, Pabst T. Randomized Phase II Study of Brentuximab-Vedotin With High-Dose Chemotherapy in CD30 Positive Lymphoma. Hematol Oncol. 2025 Nov;43(6):e70143. doi: 10.1002/hon.70143.

  PMID: 41117344 DERIVED

MeSH Terms

Conditions

Lymphoma

Interventions

Brentuximab Vedotin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Thomas Pabst, MD

  Department of Medical Oncology, University Hospital Bern

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The BAL trial consists in two parts: * single arm prospective phase I part; * randomized two-arm open-label prospective phase II part.

Study Record Dates

• First Submitted: June 12, 2017
• First Posted: June 14, 2017
• Study Start: September 1, 2018
• Primary Completion: November 2, 2023
• Study Completion: April 30, 2025
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

CH (1)