A dual-cohort, open-label, phase 2 study of brentuximab vedotin and CHP (A+CHP) in the frontline treatment of subjects with peripheral T-cell lymphoma (PTCL) with less than 10% CD30 expression

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Seagen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Jun 2021 → 12 Jan 2026

Decision date (initial)

2023-12-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Seagen Inc

External identifiers

EU CT number

2023-509155-14-00

EudraCT number

2020-002336-74

ClinicalTrials.gov

NCT04569032

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Safety

To evaluate the ORR per blinded independent central review (BICR) using Revised Response Criteria for Malignant Lymphoma criteria

Secondary objectives 6

1. To evaluate the complete response (CR) rate following completion of study treatment
2. To evaluate the progression-free survival PFS
3. To evaluate overall survival (OS)
4. To evaluate DOR
5. To evaluate ORR per BICR, using modified Lugano criteria
6. To evaluate the safety and tolerability

Conditions and MedDRA coding

Peripheral T-cell Lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Age 18 years or older
2. Newly diagnosed PTCL, excluding sALCL, per the Revised European-American Lymphoma World Health Organization (WHO) 2016 classification
3. The following non-sALCL PTCL subtypes are eligible: a. PTCL – not otherwise specified (PTCL-NOS) b. Angioimmunoblastic T-cell lymphoma (AITL) c. Adult T-cell leukemia/lymphoma (ATLL; acute and lymphoma types only, must be positive for human T cell leukemia virus 1) d. Enteropathy-associated T-cell lymphoma (EATL) e. Hepatosplenic T-cell lymphoma f. Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITCL) g. Indolent T-cell lymphoproliferative disorder (T-LPD) of the gastrointestinal (GI) tract h. Follicular T-cell lymphoma i. Nodal PTCL with T-follicular helper (TFH) phenotype 4. CD30 expression
4. CD30 expression <10% by local assessment in tumor containing lymph node or other extranodal soft tissue biopsy
5. Fluorodeoxyglucose (FDG)-avid disease by PET and measurable disease of at least 1.5 cm by CT, as assessed by the site radiologist
6. An Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
7. The following required baseline laboratory data: ● bilirubin ≤1.5X upper limit of normal (ULN) or ≤3X ULN for subjects with Gilbert’s disease or documented hepatic involvement with lymphoma ● alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3X ULN or ≤5X ULN for subjects with document hepatic involvement with lymphoma ● serum creatinine ≤2X ULN ● estimated glomerular filtration rate (eGFR) >45 mL/min/1.73 m2 using the Modification of Diet in Renal Disease (MDRD) study equation provided below. eGFR (mL/min/1.73 m2 ) = 175 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African American) Conversion to creatinine clearance (CrCl) (mL/min) from eGFR using the Mosteller body surface area (BSA) equation and dividing by 1.73 to determine dosing holds. BSA (m2 ) = (Height [cm] x Weight [kg] / 3600)1/2 CrCl (mL/min) = (eGFR [mL/min/1.73 m2 ] x BSA [m2 ])/1.73 ● absolute neutrophil count (ANC) ≥1000/µL (unless documented bone marrow involvement with lymphoma) ● platelet count ≥50,000/µL (unless documented bone marrow involvement with lymphoma)
8. The following requirements for subjects who are human immunodeficiency virus (HIV)-positive: ● CD4+ T-cell counts ≥350 cell/μL within 28 days of Day 1 ● No acquired immune deficiency syndrome-defining opportunistic infection within the past 12 months ● On established highly active antiretroviral therapy for at least 4 weeks with an HIV viral load less than 400 copies/mL within 28 days of Day 1
9. Females of childbearing potential must have a negative serum beta human chorionic gonadotrophin (β-hCG) pregnancy test result within 7 days prior to the first dose of study treatment and must agree to use an effective contraception method during the study and for at least 12 months after the last dose of cyclophosphamide or 6 months after the last dose of other study treatment, whichever is later. Females of nonchildbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy.
10. Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 12 months after the last dose of cyclophosphamide or 6 months after the last dose of other study treatment, whichever is later.
11. Subjects or their legally authorized representative must provide written informed consent. If informed consent is obtained from a legally authorized representative for a subject who is unable to provide informed consent at study entry, but the subject is later able to provide informed consent, the investigator must obtain written informed consent from the subject.

Exclusion criteria 15

1. Current diagnosis of any of the following: a. sALCL b. Primary cutaneous T-cell lymphoproliferative disorders and lymphomas c. Mycosis fungoides (MF), including transformed MF
2. History of another primary invasive cancer, hematologic malignancy, or myelodysplastic syndrome that has not been in remission for at least 3 years. Exceptions are malignancies with a negligible risk of metastasis or death (eg, 5-year OS ≥90%), such as carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
3. History of progressive multifocal leukoencephalopathy (PML).
4. Cerebral/meningeal disease related to the underlying malignancy
5. Prior treatment with brentuximab vedotin or doxorubicin.
6. Baseline peripheral neuropathy Grade  2 (per the NCI CTCAE, Version 4.03) or subjects with the demyelinating form of Charcot-Marie-Tooth syndrome.
7. Left ventricular ejection fraction less than 45% or symptomatic cardiac disease (including symptomatic ventricular dysfunction, symptomatic coronary artery disease, and symptomatic arrhythmias), or myocardial infarction within the past 6 months, or previous treatment with complete cumulative dose of >300 mg/m2 of doxorubicin.
8. Any uncontrolled Grade 3 or higher (per the National Cancer Institute’s Common Terminology Criteria for Adverse Events, NCI CTCAE Version 4.03) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study intervention. Routine antimicrobial prophylaxis is permitted.
9. Current therapy with other systemic anti-neoplastic or investigational agents. Participation in other clinical trials for any condition is not allowed. Participation in observational studies is permitted.
10. Females who are pregnant or breastfeeding
11. Subjects with a known hypersensitivity to any excipient contained in any of the drug formulations of study treatments
12. Subjects with known urinary outflow obstruction
13. Any other condition that in the opinion of the investigator would impact patient safety or ability to participate in the trial
14. Contraindications to any of the study drugs
15. Has received a live vaccine within 30 days prior to the first dose of study drug and must not receive a live vaccine within 90 days after the last dose of study drug. Vaccines other than live vaccines are permitted

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ORR per BICR following the completion of study treatment using Revised Response Criteria for Malignant Lymphoma criteria

Secondary endpoints 7

1. Complete response rate per BICR
2. PFS per BICR
3. OS
4. DOR per BICR
5. ORR per BICR, using modified Lugano criteria
6. Type, incidence, severity, seriousness, and relatedness of adverse events
7. Laboratory abnormalities

Investigational products

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

Test 1

Comparator 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Seagen Inc.

Sponsor organisation

Seagen Inc.

Address

21823 30th Drive Southeast

City

Bothell

Postcode

98021-3907

Country

United States

Scientific contact point

Organisation

Seagen Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Seagen Inc.

Contact name

Clinical Medical Lead

Third parties 6

Locations

3 EU/EEA countries · 20 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 25 files

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

Application history

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