A Randomized Phase IIb Study, Evaluating Efficacy of Salvage Therapy with Brentuximab Vedotin-ESHAP vs ESHAP in Patients with Relapsed / Refractory Classical Hodgkin’s Lymphoma, Followed by Brentuximab Vedotin Consolidation (instead of Autologous Hematopoietic Stem Cell Transplantation) in Those who Attained a Metabolic Complete Remission after Salvage Therapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Geltamo

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

29 Oct 2024 → ongoing

Decision date (initial)

2024-11-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Takeda Pharmaceuticals

External identifiers

EU CT number

2024-516149-38-00

EudraCT number

2019-002746-21

ClinicalTrials.gov

NCT04378647

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To determine metabolic complete remission (mCR) (PET-CT negative, Deauville scores 1-3) after 3 cycles of ESHAP-brentuximab vedotin (BV) vs ESHAP as salvage strategies in patients with relapsed / refractory classical Hodgkin’s Lymphoma (cHL)

Secondary objectives 15

1. To assess 2-year progression free survival (PFS) in patients diagnosed with relapsed/refractory cHL, treated with BV consolidation (autoHCT) after attaining a mCR with second line therapy
2. To evaluate 2-year overall survival (OS) in patients treated with BV consolidation after attaining a mCR with second line therapy
3. To evaluate duration of response (DOR) in patients treated with BV consolidation after attaining a mCR with second line therapy
4. To assess time to progression (TTP) in patients treated with BV consolidation after attaining a mCR with second line therapy
5. To assess differences in hematological and non-hematological toxicities between ESHAP-BV vs ESHAP in patients with relapsed / refractory cHL
6. To quantify stem cell collection yield in patients treated with ESHAP-BV vs ESHAP
7. To assess impact of second line therapy: ESHAP-BV vs ESHAP on 2-year PFS
8. To compare the outcome of patients that attained less than mCR with second line therapy (BV containing vs non-BV based therapy), [assessing their overall response rate (ORR) and CR rates after the next line of therapy and autoHCT (if applicable), time to next therapy (TTNT) and OS]
9. To assess TTNT2 (defined as the time from study enrollment to initiation of a new line of therapy due to disease progression)
10. To evaluate the prognostic impact of a negative baseline PET-CT [determined by the Deauville criteria 1, 2 and 3) on PFS and OS in patients treated with ESHAP-BV vs ESHAP only
11. To evaluate the prognostic impact of metabolic tumor volume assessed by baseline PET-CT in PFS and OS in patients treated with ESHAP-BV vs ESHAP only
12. To determine short-term and mid-term toxicity of ESHAP-BV and of BV consolidation, focusing on fertilityand secondary malignancies (evaluated yearly up to 3 years from the end of treatment)
13. To assess quality of life of patients (functional, emotional and social assessments) from the start of BV consolidation (assessed yearly up to 3 years) to the end of follow up.
14. To predict the risk to develop peripheral neuropathy (PN) and early detection of this complication by means of soluble sBDNF levels - polymorphisms
15. To explore the concordance between PEC-TC local and central evaluation

Conditions and MedDRA coding

Hodgkin Lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Male or female patients 18 years or older up to 65 years of age
2. 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
3. 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
4. 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
5. ECOG performance status 0 to 2
6. Measurable disease at time of enrolment (lymphadenopathy/ extranodal mass of at least 1.5 cm)
7. No evidence of neuropathy grade ≥2
8. 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 16

1. Lymphocyte predominant nodular Hodgkin’s lymphoma
2. Prior treatment with brentuximab vedotin
3. 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
4. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to the protocol
5. Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of progressive multifocal leukoencephalopathy (PML
6. Symptomatic neurologic disease compromising normal activities of daily living or requiring medic
7. Any sensory or motor peripheral neuropathy greater than or equal to Grade 2
8. 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%
9. Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose
10. 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
11. Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin
12. Known human immunodeficiency virus (HIV) positive (in case of Anti-HIV positive result patient cannot be included in the study)
13. 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.
14. Focal radiation therapy within 30 days prior to study recruitment
15. Major surgery within 28 days prior to randomization
16. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Treatment response based on Deauville scores 1, 2, 3 (Complete metabolic response) by PET-CT scan After the 3 first cycles of BV-ESHAP or ESHAP

Secondary endpoints 10

1. Two years Progression Free Survival (PFS): time from entry onto the study until lymphoma progression or death as a result of any cause
2. Two years Overall Survival (OS): time from entry onto the clinical trial until death as a result of any cause.
3. Duration of response (DOR): time from first documentation of CR or PR to disease progression or death from any cause, whichever occurs first
4. Time to Progression (TTP): time from study entry until lymphoma progression or death as a result of lymphoma
5. Time to Next Treatment (TTNT): time from the end of primary treatment until the onset of the next therapy
6. Time to Next Treatment 2 (TTNT2): time from study enrollment to initiation of second line of therapy due to disease progression
7. Overall response rate, complete response rate after the 3 first cycles of BV-ESHAP or ESHAP
8. Prognostic impact of metabolic tumor volume
9. Quality of life of patients
10. Safety and tolerability As assessed by type, frequency, and severity for AEs and relationship with study treatment of AEs Focusing on fertility (evaluated yearly up to 3 years from the end of treatmentand secondary malignancies (3 years follow up for secondary malignancies

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Geltamo

Sponsor organisation

Fundacion Geltamo

Address

Avenida Valdecilla Sn

City

Santander

Postcode

39008

Country

Spain

Scientific contact point

Organisation

Fundacion Geltamo

Contact name

Ana Méndez López

Public contact point

Organisation

Fundacion Geltamo

Contact name

Ana Méndez López

Third parties 6

Locations

4 EU/EEA countries · 27 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 42 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications