Brentuximab Vedotin and BeEAM High-dose Chemotherapy in Lymphomas

  • STATUS
    Recruiting
  • End date
    Jun 26, 2022
  • participants needed
    60
  • sponsor
    University Hospital Inselspital, Berne
Updated on 26 January 2021
platelet count
remission
cyclophosphamide
melphalan
cell transplantation
etoposide
neutrophil count
solid tumor
t-cell lymphoma
high dose chemotherapy
autologous hematopoietic stem cell transplant

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.

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), Szary-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

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.

Study Duration:

Phase I part will last from 3 to 18 months (permitting the enrolment of minimum of 6 patients). The Phase I will be stopped after the RP2D is established. 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.

Details
Condition Lymphoma, Lymphoproliferative Disorder, Lymphoma, Non-Hodgkin's Lymphoma, Lymphoproliferative disorders, lymphomas
Treatment brentuximab vedotin, BeEAM Regimen
Clinical Study IdentifierNCT03187210
SponsorUniversity Hospital Inselspital, Berne
Last Modified on26 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age between 18 yrs and 65 yrs?
Gender: Male or Female
Do you have Lymphoma?
Do you have any of these conditions: Lymphoproliferative disorders or Non-Hodgkin's Lymphoma or Lymphoma or Lymphoproliferative Disorder or lymphomas?
Eligible are all CD30+ malignant lymphoma, meaning lymphoma subtypes such as Hodgkin lymphomas, angioimmunoblastic T-cell lymphomas (AITL), anaplastic ALK+ T-cell lymphomas, Szary-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/L unless there is known hematologic/solid tumor marrow involvement
Platelet count 75,000/ L 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
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