Evaluation of Brentuximab Vedotin-ESHAP Versus ESHAP in Relapsed/Refractory Classical Hodgkin Lymphoma: A Phase IIb Randomized Study
- Trial ID
- 2024-516149-38-00
- Sponsor
- Fundacion Geltamo
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to determine the **metabolic complete remission** (mCR) in patients with relapsed or refractory classical Hodgkin's Lymphoma (cHL) after three cycles of ESHAP-brentuximab vedotin (BV) compared to ESHAP alone. This is clinically relevant as achieving mCR, defined by PET-CT negativity with Deauville scores of 1-3, is a critical indicator of treatment efficacy and can guide subsequent therapeutic decisions.
Secondary objectives include:
- Assessing 2-year progression-free survival (PFS) and overall survival (OS) in patients treated with BV consolidation after achieving mCR with second-line therapy.
- Evaluating the duration of response (DOR) and time to progression (TTP) in these patients.
- Comparing hematological and non-hematological toxicities between ESHAP-BV and ESHAP, and quantifying stem cell collection yield.
- Assessing the impact of second-line therapy on 2-year PFS and comparing outcomes in patients with less than mCR.
- Evaluating the prognostic impact of baseline PET-CT findings on PFS and OS, and determining short-term and mid-term toxicity focusing on fertility and secondary malignancies.
- Assessing quality of life from the start of BV consolidation to the end of follow-up, predicting the risk of developing peripheral neuropathy, and exploring the concordance between local and central PET-CT evaluations.
Participants
The clinical trial involves a total of **2 participants** diagnosed with **Hodgkin Lymphoma**, specifically targeting individuals with relapsed or refractory classical Hodgkin's Lymphoma. The study population includes both male and female subjects aged between 18 and 65 years. Participants were selected based on their ability to provide voluntary written informed consent and their compliance with specific health criteria, such as an ECOG performance status of 0 to 2 and the absence of neuropathy grade ≥2. The trial does not include a vulnerable population. Participants are required to have measurable disease at the time of enrollment, with lymphadenopathy or extranodal mass of at least 1.5 cm. Lifestyle considerations include adherence to effective contraception methods for both male and female participants, where applicable. The trial population was selected to ensure that clinical laboratory values met specified thresholds, such as an absolute neutrophil count ≥ 1,500/µL and a platelet count ≥ 75,000/µL, among others. The sponsor has not provided additional information regarding lifestyle factors such as diet or physical activity.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy of salvage therapy with **brentuximab vedotin**-ESHAP versus ESHAP alone in patients with relapsed or refractory **Hodgkin Lymphoma**. The trial aims to determine the rate of metabolic complete remission (mCR) after three cycles of treatment. The study is expected to run from June 2020 to November 2027, with the primary endpoint being the treatment response based on Deauville scores 1, 2, and 3, assessed via PET-CT scan after the initial three cycles of therapy.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, performance status, and laboratory values. Following the screening, participants will receive treatment over a maximum period of 58 days, with regular follow-up visits to monitor treatment response and safety. The end-of-study visit will assess the overall response and gather data on secondary endpoints, including progression-free survival, overall survival, and quality of life.
The expected length of participant involvement is approximately seven years, including treatment and follow-up phases. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent. Participants are required to adhere to specific contraceptive measures during the study and for six months after the last dose of the study drug to ensure safety and compliance with the trial protocol.
Treatment
The clinical trial involves the administration of **ADCETRIS**, a 50 mg powder for concentrate for solution for infusion, containing the active substance **brentuximab vedotin**. This experimental medication is formulated as a **solution for infusion** and is administered via **intravenous perfusion**. The maximum daily dose is 180 mg, with a total maximum dose of 180 mg over the treatment period. The treatment duration is set for a maximum of 58 days. The primary and secondary packaging, including vials and boxes, are labeled specifically for the trial. **Brentuximab vedotin** is a monoclonal antibody against human CD30, covalently linked to the cytotoxin monomethylauristatin E, and is classified under the ATC code L01XC12. The pharmaceutical product is manufactured by Takeda Pharma A/S and is not a pediatric formulation.
In addition to the experimental treatment, the study includes a comparator treatment, ESHAP, which is a standard-of-care therapy for patients with relapsed or refractory classical Hodgkin's lymphoma. The trial aims to evaluate the efficacy of salvage therapy with **brentuximab vedotin** combined with ESHAP versus ESHAP alone. The objective is to determine the rate of metabolic complete remission, defined as PET-CT negative with Deauville scores of 1-3, after three cycles of the respective treatments. Compliance with the dosing schedule and administration is monitored throughout the trial to ensure adherence to the protocol.
Efficacy
Efficacy in this clinical trial will be assessed primarily through the evaluation of **metabolic complete remission (mCR)**, defined as PET-CT negative with Deauville scores of 1 to 3, after three cycles of ESHAP-brentuximab vedotin (BV) compared to ESHAP alone in patients with relapsed or refractory classical Hodgkin's Lymphoma. The primary endpoint is the treatment response based on these Deauville scores, measured by PET-CT scan following the initial three cycles of treatment.
Secondary endpoints include a range of efficacy parameters: two-year Progression-Free Survival (PFS), Overall Survival (OS), Duration of Response (DOR), Time to Progression (TTP), Time to Next Treatment (TTNT), and Time to Next Treatment 2 (TTNT2). Additionally, the overall response rate and complete response rate after the first three cycles of BV-ESHAP or ESHAP will be evaluated. The prognostic impact of metabolic tumor volume, quality of life, and safety and tolerability, including the assessment of adverse events and their relationship with the study treatment, will also be considered. These secondary endpoints will provide a comprehensive understanding of the treatment's efficacy and its impact on patient outcomes.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or female patients 18 years or older up to 65 years of age
- Voluntary written informed consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
- Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse
- Male patients, even if surgically sterilized, (i.e., status post-vasectomy) agree to practice effective barrier contraception during the entire study period and through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse
- ECOG performance status 0 to 2
- Measurable disease at time of enrolment (lymphadenopathy/ extranodal mass of at least 1.5 cm)
- No evidence of neuropathy grade ≥2
- Clinical laboratory values as specified below within 7 days before the first dose of study drug: 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
- Lymphocyte predominant nodular Hodgkin’s lymphoma
- Prior treatment with brentuximab vedotin
- Female patient who are both lactating and breast-feeding or have a positive serum pregnancy test during the screening period or a positive pregnancy test on Day 1 before first dose of study drug
- Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to the protocol
- Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of progressive multifocal leukoencephalopathy (PML
- Symptomatic neurologic disease compromising normal activities of daily living or requiring medic
- 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 enrollment; New York Heart Association (NYHA) Class III or IV heart failure; 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%
- Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose
- Patients that have not completed any prior treatment chemotherapy and/or other investigational agents within at least 5 half-lives (or 28 days if the half-lives are unknown) 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
- Known human immunodeficiency virus (HIV) positive (in case of Anti-HIV positive result patient cannot be included in the study)
- Known hepatitis B surface or core antigen-positive (HBsAg/ HBcAg). In case of Anti HBc positive result, DNA-HBV must be determined and negative result will allow patient inclusion. Known or suspected active hepatitis C infection. In case of Anti-HCV positive result, RNA-HCV must be determined and negative result will allow patient inclusion.
- Focal radiation therapy within 30 days prior to study recruitment
- Major surgery within 28 days prior to randomization
- Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Recruiting | 05 Jun 2020 | 4 |
 Croatia | Not Recruiting | 05 Jun 2020 | 1 |
 Greece | Not Recruiting | 05 Jun 2020 | 3 |
 Spain | Not Recruiting | 05 Jun 2020 | 141 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
ADCETRIS 50 mg powder for concentrate for solution for infusion | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS PERFUSION USE | 180 | 58 | PRD2487300 |