An Efficacy and Safety Proof of Concept Study of Daratumumab in Relapsed/Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma

• Register: EUCTR
• Last refreshed on: 10 July 2017
• Main ID: EUCTR2014-005299-26-BE
• Date of registration: 05/05/2015
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V.
• Public title: An Efficacy and Safety Proof of Concept Study of Daratumumab in Relapsed/Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma
• Scientific title: An Open Label, Phase 2 Study to Evaluate Efficacy and Safety of Daratumumab in Relapsed or Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma
• Date of first enrolment: 08/06/2015
• Target sample size: 210
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005299-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, France, Korea, Republic of, Netherlands, Turkey, United States

Contacts

• Name: Clinical Registry group
• Affiliation: Janssen-Cilag International N.V.

• Name: Clinical Registry group
• Affiliation: Janssen-Cilag International N.V.

Key inclusion & exclusion criteria

Inclusion criteria:
Has diagnosis and prior treatment for each non-hodgkin's lymphoma (NHL) subtype as
defined below: Mantle cell lymphoma (MCL): pathologically verified diagnosis of MCL based on local
pathology report, relapsed or refractory disease after at least 2 but not more than 5 prior lines of therapy,
including at least one cycle of ibrutinib therapy and documented progressive disease (PD) during or after
ibrutinib treatment or participants who could not tolerate ibrutinib (ie, discontinued ibrutinib due to adverse
events [AEs]), b) Diffuse large B cell lymphoma (DLBCL): pathologically confirmed diagnosis of nontransformed
DLBCL, and c) relapsed or refractory disease; participants are not eligible or considered a
candidate for high-dose chemotherapy and autologous stem cell transplantation due to other organ
dysfunction or comorbidities (especially pulmonary or cardiac), c) Follicular lymphoma (FL): pathologically
confirmed diagnosis of FL of Grade 1, 2, or 3a according to World Health Organization (WHO) criteria
without pathological evidence of transformation, and relapsed disease after at least two prior systemic
therapies including one anti-CD20 containing combination regimen - At least 1 measurable site of disease -
Expression of CD38 by immunohistochemistry on fresh or archived tumor sample by central assessment:
a) Stage 1: participants whose tumors are more than or equal to (>=) 50 percent (%) positive for CD38, b)
Stage 2: participants whose tumors are >=1% positive for CD38 - Participant must have an ECOG
performance status score of 0 or 1 - Women of childbearing potential must commit to either abstain
continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control
simultaneously. A woman of childbearing potential must have a negative serum or urine pregnancy test
within 14 days prior to Cycle 1 Day 1. A man who is sexually active with a woman of childbearing potential
must agree to always use condom during sexual intercourse, and all men must also not donate sperm
during the study and for 4 months after receiving the last dose of study drug
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 140
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

Exclusion criteria:
•Known central nervous system lymphoma
•Prior anti-tumor therapy including (all times measured prior to start of study drug):
-nitrosoureas within 6 weeks
-chemotherapy within 3 weeks
-therapeutic antibodies within 4 weeks
-radio- or toxin-immunoconjugates within 10 weeks
-radiation therapy within 2 weeks
-investigational agents within 3 weeks, unless antibody this should be within 4 weeks
-Daratumumab or other anti-CD38
•Participant has a history of malignancy (other than NHL) within 5 years before the screening
period (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix,
non-muscle invasive bladder cancer (papillary neoplasms of low malignant potential and primary noninvasive
tumors), or malignancy that in the opinion of the investigator, with concurrence with the sponsor's
medical monitor, is considered cured with minimal risk of recurrence within 3 years) - Participant has known
chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) less
than (<) 50% predicted normal. Note that FEV1 testing is required for patients suspected of having COPD
and participants must be excluded if FEV1 <50% b) Participant has known moderate or severe persistent
asthma within 2 years (see Attachment 4: NHLBI table of asthma severity), or currently has uncontrolled
asthma of any classification. (Note that participants who currently have controlled intermittent asthma or
controlled mild persistent asthma are allowed in the study)
therapies



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Relapsed or Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma
MedDRA version: 18.0 Level: HLT Classification code 10012819 Term: Diffuse large B-cell lymphomas System Organ Class: 100000004851
MedDRA version: 18.0 Level: HLT Classification code 10016903 Term: Follicle centre lymphomas, follicular grade I, II, III System Organ Class: 100000004851
MedDRA version: 18.0 Level: HLT Classification code 10026798 Term: Mantle cell lymphomas System Organ Class: 100000004851

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Daratumumab
Product Code: HuMax-CD38
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Daratumumab
CAS Number: 945721-28-8
Current Sponsor code: JNJ-54767414 (Daratumumab)
Other descriptive name: HUMAX-CD38
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Primary end point(s): Number of Participants With Overall response rate (ORR)

Timepoint(s) of evaluation of this end point: Approximately 3.5 years

Main Objective: The study will evaluate daratumumab separately in three relapsed or refractory NHL subtypes
that are CD38 positive: MCL, DLBCL, and FL. There are two main objectives:
-To assess overall response rate (ORR, including complete response (CR) and partial
response (PR)), of daratumumab in subjects with CD38+ disease in each NHL subtype.
-To evaluate association between ORR and CD38 expression level in order to determine a
threshold for CD38 expression level in each NHL subtype, above which daratumumab
activity is enhanced.

Secondary Objective: For each subtype of NHL, the secondary objectives are:
-To assess the duration of response (DoR), PFS and OS
-To assess time to response
-To assess and correlate the CD38 expression level with DoR, PFS and OS
-To assess pharmacokinetics of daratumumab
-To assess immunogenicity of daratumumab
-To assess the safety profile of daratumumab

Secondary Outcome(s)

Secondary end point(s): 1. Duration of response (DoR)
2. Progression Free Survival (PFS)
3. Overall survival (OS)
4. Time to response

Timepoint(s) of evaluation of this end point: Approximately 3.5 years

Secondary ID(s)

54767414LYM2001

Source(s) of Monetary Support

Janssen Research & Development, LLC