CHP-BV Followed by Consolidation With High-dose Therapy / ASCT as Frontline Treatment of Patients With EATL Type 1. (EATL-001)

Phase 2 Study of Brentuximab Vedotin Associated With CHP Followed by Consolidation With High-dose Therapy / Autologous Stem-cell Transplantation as Frontline Treatment of Patients With Enteropathy-associated T-cell Lymphoma Type 1.

It has been recently reported that EATL type 1, but not refractory coeliac disease, strongly expressed CD30 and might benefit from brentuximab vedotin. Since the safety profile of the combination brentuximab vedotin and CHP is known and since the role of etoposide as part of induction regimen is not demonstrated, the investigator will assess the efficacy and toxicity of the combination brentuximab vedotin and CHP followed by HDT/ASCT, as frontline treatment of EATL.

Study Overview

• Status: Active, not recruiting
• Conditions: Enteropathy Associated T-cell Lymphoma
• Intervention / Treatment: Drug: Brentuximab Vedotin

Detailed Description

Brentuximab vedotin is an anti-CD30 monoclonal antibody conjugated to the cytotoxic drug monomethyl auristatin E. It is currently evaluated in combination with multi-agent chemotherapy as frontline treatment of systemic ALCL (sALCL) and other CD30-positive mature T cell and NK cell lymphomas. Preliminary results of this phase 1 study have been presented at the 2012 ASH Annual Meeting: 26 patients have been treated with combination brentuximab vedotin and CHP. Nineteen of 26 patients had a diagnosis of sALCL and 7 patients had a diagnosis of another mature Tor NK-cell lymphoma (EATL, n=1). The maximum tolerated dose of brentuximab vedotin in combination with CHP was not exceeded at 1.8 mg/kg IV. Adverse events were manageable. All patients achieved an objective response, with 23 patients (88%) achieving a complete response (CR). All 7 non-sALCL patients achieved a CR.

Finally, it has been recently reported that EATL type 1, but not refractory coeliac disease, strongly expressed CD30 and might benefit from brentuximab vedotin. Since the safety profile of the combination brentuximab vedotin and CHP is known and since the role of etoposide as part of induction regimen is not demonstrated, the investigator will assess the efficacy and toxicity of the combination brentuximab vedotin and CHP followed by HDT/ASCT, as frontline treatment of EATL.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hermine Olivier; Phone Number: +33 1 44 49 54 16; Email: oliver.hermine@aphp.fr

Study Locations

• France
  • Paris, France
    • Hopital Necker - Enfants Malades

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

1. Histologically confirmed diagnosis of EATL based on criteria established by the World Health Organization (WHO) 2016 Classification of Tumors of Haematopoietic and Lymphoid Tissues.
2. EATL should be CD30-positive with a threshold of 10%.
3. Patients aged ≥ 18 years and < 70 years at the time of study entry.
4. ECOG performance status 0 to 3 at time of study entry.
5. Left Ventricular Ejection Fraction (LVEF) ≥ 45% measured by bidimensional echography or radionuclide ventriculography (MUGA scan).

Main Exclusion Criteria:

1. Participants must not have been treated with any prior chemotherapy for EATL. Patients with previous treatment for refractory celiac disease (i.e., immunosuppressive or immunoregulatory drugs) may be included.
2. Known central nervous system involvement by EATL.
3. Active chronic hepatitis B or C.
4. HIV positive serology.
5. HTLV-1 positive serology.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brentuximab Vedotin; The first part of the treatment (induction) will evaluate BV-CHP. The second part of the treatment (consolidation) will use standard drugs for the treatment of lymphoma. HDT will consist of BEAM conditioning regimen (or BAM if carmustine is not available). Management of HDT/ASCT will be done according to standard practice.	Drug: Brentuximab Vedotin; The first part of the treatment (induction) will evaluate BV-CHP. The second part of the treatment (consolidation) will use standard drugs for the treatment of lymphoma. HDT will consist of BEAM conditioning regimen (or BAM if carmustine is not available). Management of HDT/ASCT will be done according to standard practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the 2-year progression-free survival	2-year progression-free survival (PFS)	4 years

Collaborators and Investigators

• Sponsor: Imagine Institute
• Collaborators: Takeda
• Investigators: Principal Investigator: Hermine Olivier, Hopital Necker-Enfants Malades

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2018
• Primary Completion (Estimated): February 6, 2024
• Study Completion (Estimated): February 6, 2024

Study Registration Dates

• First Submitted: July 12, 2017
• First Submitted That Met QC Criteria: July 12, 2017
• First Posted (Actual): July 14, 2017

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Gastrointestinal Diseases; Lymphoma; Intestinal Diseases; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Enteropathy-Associated T-Cell Lymphoma; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immunoconjugates; Immunotoxins; Brentuximab Vedotin
• Other Study ID Numbers: IMIS2015-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No