Phase 3 Frontline Therapy Trial in Patients With Advanced Classical Hodgkin Lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Takeda Development Center Americas Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Jan 2013 → 3 Feb 2026

Decision date (initial)

2024-02-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Takeda Development Center Americas, Inc.

External identifiers

EU CT number

2023-506419-16-00

EudraCT number

2011-005450-60

WHO UTN

U1111-1161-4937

ClinicalTrials.gov

NCT01712490

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Pharmacodynamic, Therapy, Efficacy, Pharmacoeconomic, Pharmacogenomic, Safety

To compare the modified progression-free survival (mPFS) obtained with brentuximab vedotin (ADCETRIS®) plus AVD (doxorubicin [Adriamycin], vinblastine, and dacarbazine; abbreviated A+AVD) versus that obtained with ABVD (doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine) for the frontline treatment of advanced classical Hodgkin lymphoma (HL)

Secondary objectives 1

1. Overall survival rate. To determine if A+AVD improves overall survival (OS) versus that obtained with ABVD

Conditions and MedDRA coding

Advanced Classical Hodgkin Lymphoma

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Male or female patients 18 years or older.
2. Treatment-naïve, HL patients with Ann Arbor Stage III or IV disease
3. Histologically confirmed classical HL according to the current World Health Organisation Classification (nodular sclerosis, mixed cellularity, lymphocyte rich, lymphocyte depleted, or classical Hodgkin lymphoma, NOS [not otherwise specified]).
4. ECOG performance status ≤ 2
5. Patients must have had bidimensional measurable disease as documented by radiographic technique (spiral CT preferred) per the International Working Group Revised Criteria for Response Assessment for Malignant Lymphoma (Cheson 2007).
6. Female patients who: •Were postmenopausal for at least 1 year before the screening visit, OR • Were surgically sterile, OR • If they were of childbearing potential, agreed 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 • Agreed to practice true abstinence, when this was in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal were not acceptable methods of contraception.) Male patients, even if surgically sterilized (ie, status postvasectomy), who: • Agreed to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, OR • Agreed to practice true abstinence, when this was in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal were not acceptable methods of contraception.)
7. Voluntary written consent was required 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.
8. Suitable venous access for the study-required blood sampling, including PK sampling.
9. Clinical laboratory values as specified within 7 days before the first dose of study drug: • Absolute neutrophil count ≥ 1,500/μL unless there was known HL marrow involvement • Platelet count ≥ 75,000/μL unless there was known HL marrow involvement • Total bilirubin < 1.5 X the upper limit of normal (ULN) unless the elevation was known to be due to Gilbert syndrome. • ALT or AST < 3 X the upper limit of the normal range. AST and ALT could be elevated up to 5 times the ULN if their elevation could be reasonably ascribed to the presence of HL in liver. • Serum creatinine < 2.0 mg/dL and/or creatinine clearance or calculated creatinine clearance > 40 mL/minute (refer to Section 15.3). • Hemoglobin ≥ 8 g/dL.

Exclusion criteria 13

1. Nodular lymphocyte predominant Hodgkin lymphoma
2. Female patients who were both lactating and breastfeeding or who had a positive serum pregnancy test during the screening period or a positive pregnancy test on Day 1 before first dose of study drug
3. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
4. Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of PML
5. Symptomatic neurologic disease compromising normal activities of daily living or requiring medications
6. Any sensory or motor peripheral neuropathy
7. Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose
8. Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy (eg, immunoglobulin replacement, other monoclonal antibody therapies) within 12 weeks of first study drug dose
9. Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin or any component of ABVD
10. Known human immunodeficiency virus (HIV) positive
11. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection
12. Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and had any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type were not excluded if they had undergone complete resection.
13. Any of the following cardiovascular conditions or values within 6 months before the first dose of study drug: • A left-ventricular ejection fraction < 50% • Myocardial infarction within 2 years of randomization • New York Heart Association (NYHA) Class III or IV heart failure (see Section 15.4). • 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Modified PFS per IRF assessment using the Revised Response Criteria for Malignant Lymphoma

Secondary endpoints 1

1. Overall survival

Investigational products

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

Test 1

Comparator 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Takeda Development Center Americas Inc.

Sponsor organisation

Takeda Development Center Americas Inc.

Address

95 Hayden Avenue

City

Lexington

Postcode

02421-7942

Country

United States

Scientific contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Bipin Savani

Public contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Takeda Development Center Americas Inc.

Third parties 5

Locations

9 EU/EEA countries · 48 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 20 files

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

Application history

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