B-MAD Chemotherapy in Newly-diagnosed Extranodal NK/ T-cell Lymphoma

NCT03246750 | Completed Phase 1

• 1 other identifier: TLSG-2017-T01
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Study Title: Phase I/II study of brentuximab vedotin and methotrexate/ L-asparaginase/ dexamethasone (B-MAD) chemotherapy in patients with newly-diagnosed Extranodal NK/T-cell Lymphoma Phase: I/II Number of Patients: 36 Study Objectives Primary

• To determine the safety and optimal dose of brentuximab vedotin when use in combination with methotrexate, L-asparaginase and dexamethasone in the treatment of newly-diagnosed ENKTL patients Secondary
• To evaluate the clinical efficacy of this regimen
• To access the overall responses including overall response rate (ORR), disease-free survival (DSF), progression-free survival (PFS). Overview of Study Design: Open-label, multicenter, non-randomized, 3+3 dose escalation study of brentuximab vedotin in combination with fixed-dose MAD chemotherapy. The first cycle will be evaluated for the determination of the recommended phase II dose. Patients will be received the treatment according to the stage of disease as follows:
• Patients with localized ENKTL (stage IE or stage IIE) will receive involved-field radiation (IRFT) with concomitant weekly intravenous Cisplatin. Three to five weeks after the completion of IFRT and cisplatin, B-MAD (Brentuximab vedotin, Methotrexate, L-asparaginase and Dexamethasone) regimen will be given every 21 days for 3 cycles.
• Patients with advanced ENKTL (stage III or stag IV) will receive B-MAD every 21 days for 6 cycles. Study Population: Patients with newly-diagnosed ENKTL will be screened for enrollment. Duration of Study: 3 years

Conditions

Extranodal NK/T-cell Lymphoma

Keywords

Brentuximab Vedotin

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Patients will be assessed for dose-limiting toxicity (DLT) during the first cycle. DLTs are described as follows: For non-hematologic toxicities • Any related non-hematologic events of grade 3 or higher, with the exception of: * grade 3 fatigue * grade 3 or 4 nausea and vomiting lasting than 24 hours * grade 3 non-hematologic laboratory abnormalities resolving to grade 1 or baseline within 14 days * grade 3 or 4 allergic or hypersensitivity reaction For hematologic toxicities * Related grade 4 neutropenia lasting \> 7 days * Related grade 3 febrile neutropenia requiring antibiotics * Related grade 4 febrile neutropenia * Related grade 4 thrombocytopenia

  At the end of Cycle 1 (each cycle is 21 days)

Secondary Outcomes (3)

• Treatment responses

  At 7th week after last BV dosing

• Disease-free survival

  1 year

• Progression-free survival

  1 year

Study Arms (1)

B-MAD chemotherapy

EXPERIMENTAL

Brentuximab Vedotin, Methotrexate, L-Asparaginase, and Dexamethasone

Drug: B-MAD chemotherapy

Interventions

B-MAD chemotherapy DRUG

B-MAD chemotherapy

Also known as: Involved field radation, cisplatin

B-MAD chemotherapy

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with previously untreated ENKTL as defined by the World Health Organization (WHO) classification
• Age 18-60 years
• Localized (stage I, II) or advanced (stage III, IV) disease
• Adequate organ function
• Signed informed consent

You may not qualify if:

• Patients with other subtypes of non-Hodgkin lymphoma, including myeloid/NK cell precursor acute leukemia, blastic NK cell lymphoma/precursor NK cell lymphoblastic leukemia, aggressive NK cell leukemia, and peripheral T cell lymphoma, unspecified
• Prior chemotherapy or radiotherapy for ENKTL
• Seropositivity for HIV and severe infection
• Prior or other concomitant malignant tumors
• Pregnant or breastfeeding patients
• Evidence of any other disease or medical conditions that contraindicate use of the study drug, or patients at high risk from treatment complications
• Patients suffering from psychiatric disorders

Sponsors & Collaborators

• The Thai Lymphoma Study Group: lead
• Takeda: collaborator

Study Sites (1)

King Chulalongkorn Memorial Hospital

Bangkok, 10330, Thailand

Location

MeSH Terms

Conditions

Lymphoma, Extranodal NK-T-Cell

Interventions

Cisplatin

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Udomsak Bunworasate, MD

  Chulalongkorn University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: A.Prof.

Model Details: 3+3 dose escaltion design

Study Record Dates

• First Submitted: July 13, 2017
• First Posted: August 11, 2017
• Study Start: January 30, 2019
• Primary Completion: April 10, 2024
• Study Completion: April 10, 2024
• Last Updated: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)