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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02927925

Enrollment

Registered

2016-10-07

Start date

2017-02-14

Completion date

2020-01-07

Last updated

2021-01-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lymphoma

Brief summary

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).

Interventions

DRUGDaratumumab

Participants will receive daratumumab 16 mg/kg as intravenous infusion.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Overall Response	Up to 2 years and 11 months	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.

Secondary

Measure	Time frame	Description
Progression Free Survival (PFS)	Up to 2 years and 11 months	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.
Duration of Response (DoR)	Up to 2 years and 11 months	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.
Time to Response	Up to 2 years and 11 months	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.
Overall Survival (OS)	Up to 2 years and 11 months	OS was defined as the duration from the date of the first daratumumab dose to the date of death.
Percentage of Participants With Complete Response (CR)	Up to 2 years and 11 months	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.
Number of Participants With Clinically Significant Change in Vital Signs	Up to 2 years and 11 months	Number of participants with clinically significant change in vital signs (blood pressure, temperature, pulse rate, and weight) was reported.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities	Up to 2 years and 11 months	Number of participants with clinically significant ECG abnormalities were reported.
Number of Participants With Clinically Significant Change in Physical Finding	Up to 2 years and 11 months	Number of participants with clinically significant change in physical finding was reported.
Number of Participants With Clinically Significant Change in Laboratory Parameters	Up to 2 years and 11 months	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.
Number of Participants With Treatment Emergent Adverse Events (TEAE) as a Measure of Safety and Tolerability	Up to 2 years and 11 months	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.

Countries

China, Hong Kong, Singapore, South Korea, Taiwan

Participant flow

Participants by arm

Arm	Count
Daratumumab Participants received daratumumab 16 milligrams per kilogram (mg/kg) as an 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 (up to 392 Days).	32
Total	32

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	16
Overall Study	Disease progression at clinical cutoff	1
Overall Study	Other	3
Overall Study	Physician Decision	1
Overall Study	Withdrawal by Subject	11

Baseline characteristics

Characteristic	Daratumumab
Age, Continuous	54.8 years STANDARD_DEVIATION 14
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	32 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	32 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	0 Participants
Region of Enrollment CHINA	7 Participants
Region of Enrollment HONG KONG	1 Participants
Region of Enrollment REPUBLIC OF KOREA	17 Participants
Region of Enrollment SINGAPORE	2 Participants
Region of Enrollment TAIWAN, PROVINCE OF CHINA	5 Participants
Sex: Female, Male Female	9 Participants
Sex: Female, Male Male	23 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	21 / 32
other Total, other adverse events	31 / 32
serious Total, serious adverse events	17 / 32

Outcome results

Primary

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.