A Study to Assess the Clinical Efficacy and Safety of Daratumumab in Participants With Relapsed or Refractory Natural Killer/T-Cell Lymphoma (NKTCL), Nasal Type

An Open Label, Phase 2 Study to Assess the Clinical Efficacy and Safety of Daratumumab in Patients With Relapsed or Refractory Natural Killer/T-Cell Lymphoma, Nasal Type

The purpose of this study is to assess the clinical efficacy and safety of daratumumab in relapsed or refractory natural killer/T-cell lymphomas (NKTCL).

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: Daratumumab

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing, China, 100021
    • Cancer Hospital, Chinese Academy of Medical Sciences
  • Guangzhou, China, 510060
    • Sun Yat-sen University Cancer Center
  • Hangzhou, China, 310003
    • 1st Affiliated Hospital of Zhejiang University Medical College
  • Shanghai, China, 200025
    • Ruijin Hospital, Shanghai Jiao Tong University
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital, University of Hong Kong
• Korea, Republic of
  • Goyang-si, Korea, Republic of, 10408
    • National Cancer Center
  • Seoul, Korea, Republic of, 3080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of, 5505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • Seoul ST. Mary's Hospital
• Singapore
  • Singapore, Singapore, 169608
    • Singapore General Hospital
  • Singapore, Singapore, 169610
    • National Cancer Centre Singapore
• Taiwan
  • Changhua, Taiwan, 50006
    • Changhua Christian Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Documented as histologically confirmed extranodal natural killer/T-cell lymphomas (NK/T)-cell lymphoma, nasal type according to the World Health Organization (WHO) classification and the pathology report will be verified by the Sponsor
• Failed at least 1 line of chemotherapy and who, according to treating physician or investigator, is not candidate to receive other treatment modalities
• At least 1 measurable site of disease
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2 and life expectancy greater than or equal to (>=) 3 months

Exclusion Criteria:

• Received daratumumab or other antiCD38 therapies previously
• Previous allogenic stem cell transplant or autologous stem cell transplantation within 12 weeks before the first administration of the study drug
• Clinical symptoms of central nervous system involvement
• Known chronic obstructive pulmonary disease, known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification
• Clinically significant cardiac disease, including:Myocardial infarction within 6 months before the first study agent administration, or unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV); Uncontrolled cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE] [most recent version] Grade 3 or higher) or clinically significant ECG abnormalities; Screening 12-lead ECG showing a baseline QT interval as corrected QTc >470 msec
• Seropositive for human immunodeficiency virus
• Seropositive for hepatitis B or hepatitis C
• Abnormal laboratory values according to protocol defined parameters at screening

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: Daratumumab; Participants will receive daratumumab 16 milligram per kilogram (mg/kg) by intravenous (IV) infusion once weekly for 8 weeks, then every 2 weeks for 16 weeks, then every 4 weeks thereafter until study drug discontinuation due to progressive disease (PD), consent withdrawal or unacceptable toxicity.	Drug: Daratumumab; Participants will receive daratumumab 16 mg/kg as intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Overall Response	Overall response was defined as the percentage of participants who achieved complete response (CR) or partial response (PR) per Revised Criteria for Response Assessment of Hodgkin and non-Hodgkin lymphoma: LUGANO classification based on blinded independent central review (BICR). As per Revised Response Criteria for Malignant Lymphoma, Lymph node measurements were taken from Computed Tomography (CT), CT portion of the Positron Emission Tomography/Computed Tomography (PET/CT), where applicable. CR: complete disappearance of all evidence of disease; PR as a greater than (>) 50 percent (%) decrease in the sum of the products of the maximal perpendicular diameters of measured lesions (SPD) and no new sites.	Up to 2 years and 11 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Complete Response (CR)	CR was defined as the percentage of participants who achieved CR as per Revised Criteria for Response Assessment of Hodgkin and non-Hodgkin lymphoma: LUGANO classification based on BICR. CR was a complete disappearance of all evidence of disease.	Up to 2 years and 11 months
Progression Free Survival (PFS)	PFS was defined as the duration from the date of the first daratumumab dose to the date of progression/relapse or death, whichever came first. Progressive disease (PD) was defined as any new lesion greater than (>) 1.5 centimeter (cm) in any axis or greater than or equal to (>=) 50 percent (%) increase in previously involved sites.	Up to 2 years and 11 months
Duration of Response (DoR)	DoR was defined as duration from the date of the initial documentation of a response to the date of first documented evidence of progressive disease (PD) (or relapse for participants who experienced CR). PD was defined as any new lesion >1.5 cm in any axis or >= 50% increase in previously involved sites.	Up to 2 years and 11 months
Time to Response	Time to response was defined as the duration from the date of the first dose of daratumumab to the earliest date that a response (CR/PR based on BICR) is first documented. CR was defined as complete disappearance of all evidence of disease; PR as a greater than (>) 50 percent (%) decrease in the sum of the products of the maximal perpendicular diameters of measured lesions (SPD) and no new sites.	Up to 2 years and 11 months
Overall Survival (OS)	OS was defined as the duration from the date of the first daratumumab dose to the date of death.	Up to 2 years and 11 months
Number of Participants With Treatment Emergent Adverse Events (TEAE) as a Measure of Safety and Tolerability	An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAE were defined as AEs with onset during the treatment period or that are a consequence of a pre-existing condition that has worsened since baseline.	Up to 2 years and 11 months
Number of Participants With Clinically Significant Change in Vital Signs	Number of participants with clinically significant change in vital signs (blood pressure, temperature, pulse rate, and weight) was reported.	Up to 2 years and 11 months
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities	Number of participants with clinically significant ECG abnormalities were reported.	Up to 2 years and 11 months
Number of Participants With Clinically Significant Change in Physical Finding	Number of participants with clinically significant change in physical finding was reported.	Up to 2 years and 11 months
Number of Participants With Clinically Significant Change in Laboratory Parameters	Number of participants with clinically significant change in hematology (WBC, hemoglobin, platelets, neutrophils, and lymphocytes) and biochemistry (alanine transaminase [ALT], aspartate transaminase [AST], sodium, potassium, bilirubin, alkaline phosphatase, calcium laboratory parameters were reported.	Up to 2 years and 11 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Huang H, Zhu J, Yao M, Kim TM, Yoon DH, Cho SG, Eom HS, Lim ST, Yeh SP, Song Y, Kwong YL, Kim JS, Jin J, Shi Y, Kim H, Qing M, Zhou T, Gao G, Dong Z, Qi M, Kim WS. Daratumumab monotherapy for patients with relapsed or refractory natural killer/T-cell lymphoma, nasal type: an open-label, single-arm, multicenter, phase 2 study. J Hematol Oncol. 2021 Feb 15;14(1):25. doi: 10.1186/s13045-020-01020-y.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2017
• Primary Completion (Actual): January 2, 2020
• Study Completion (Actual): January 7, 2020

Study Registration Dates

• First Submitted: October 6, 2016
• First Submitted That Met QC Criteria: October 6, 2016
• First Posted (Estimate): October 7, 2016

Study Record Updates

• Last Update Posted (Actual): January 14, 2021
• Last Update Submitted That Met QC Criteria: December 18, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Antineoplastic Agents; Daratumumab
• Other Study ID Numbers: CR108237; 54767414NKT2001 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No