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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02413489




Registration number
NCT02413489
Ethics application status
Date submitted
7/04/2015
Date registered
10/04/2015
Date last updated
26/06/2018

Titles & IDs
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
Secondary ID [1] 0 0
54767414LYM2001
Secondary ID [2] 0 0
CR106660
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoma, Mantle-Cell 0 0
Lymphoma, Large B-Cell, Diffuse 0 0
Lymphoma, Follicular 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Daratumumab

Experimental: Daratumumab - Participants will receive daratumumab (16 milligram per kilogram [mg/kg]) as intravenous infusion once every week for 8 weeks; then once every other week for 16 weeks; thereafter once every 4 weeks until documented progression, unacceptable toxicity, or study end.


Treatment: Drugs: Daratumumab
Daratumumab 16 mg/kg will be administered as intravenous infusion to participants once every week for 8 weeks; then once every other week for 16 weeks; thereafter once every 4 weeks until documented progression, unacceptable toxicity, or study end.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR) - ORR was defined as the percentage of participants who achieved complete response (CR) or partial response (PR). 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), or Magnetic resonance imaging (MRI) scans where applicable. CR is 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.
Timepoint [1] 0 0
After the first dose until disease progression, withdrawal of consent from study participation, or the end of study (approximately 1.9 years)
Secondary outcome [1] 0 0
Duration of Response - Duration of response was the duration from the date of the initial documentation of a response to the date of first documented evidence of progressive disease (PD). PD is defined as any new lesion >1.5 centimeter (cm) in any axis or greater than or equal to (>=) 50% increase in previously involved sites.
Timepoint [1] 0 0
Approximately 1.9 years
Secondary outcome [2] 0 0
Progression Free Survival (PFS) - PFS was defined as the duration from the date of the first daratumumab dose to the date of progression or death, whichever comes first.
Timepoint [2] 0 0
Approximately 1.9 years
Secondary outcome [3] 0 0
Overall Survival (OS) - Overall survival was defined as the duration from the date of the first daratumumab dose to the date of death.
Timepoint [3] 0 0
Approximately 1.9 years
Secondary outcome [4] 0 0
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) is first documented.
Timepoint [4] 0 0
Approximately 1.9 years

Eligibility
Key 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 prior
lines of therapy, including at least 1 cycle of Bruton's tyrosine kinase (BTK)
inhibitor therapy and documented progressive disease (PD) during or after BTK
inhibitor treatment or participants who could not tolerate BTK inhibitor [ie,
discontinued BTK inhibitor due to adverse events (AEs)], b) Diffuse large B cell
lymphoma (DLBCL): pathologically confirmed diagnosis of non-transformed DLBCL, and
relapsed or refractory disease; for those participants who have not received HDT/ASCT
are not eligible for HDT/ASCT due to comorbidities, 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

- Participants must have available archival or fresh tumor tissue or both to submit to a
central laboratory for CD38 assay. Expression of CD38 is measured by
immunohistochemistry on fresh or archived tumor sample by central assessment using a
CD38 investigational IHC assay under development: a) Stage 1: participants whose
tumors are more than or equal to (>=) 50 percent (%) positive for CD38, b) Stage 2:
participant has less than (<) 50% CD38+ or greater than (>) 50% CD38+ depending on the
distribution of CD 38 expression of enrolled participants during Stage 2. The sponsor
will advise on which eligibility criterion is permitted during the enrollment period

- Participant must have an ECOG performance status score of 0 or 1

- Women of childbearing potential must be practicing a highly effective method of birth
control consistent with local regulations regarding the use of birth control methods
for participants participating in clinical studies: example, established use of oral,
injected or implanted hormonal methods of contraception; placement of an intrauterine
device (IUD) or intrauterine system (IUS); barrier methods: condom with spermicidal
foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps)
with spermicidal foam/gel/film/cream/suppository; male partner sterilization (the
vasectomized partner should be the sole partner for that participant); true abstinence
(when this is in line with the preferred and usual lifestyle of the participant)
during and after the study (3 months after the last dose of any component of the
treatment regimen)

- A woman of childbearing potential must have a negative serum or urine pregnancy test
within 14 days before commencing treatment. Females of reproductive potential must
commit either to abstain continuously from heterosexual sexual intercourse or to use 2
methods of reliable birth control simultaneously

- A man who is sexually active with a woman of childbearing potential and has not had a
vasectomy must agree to use a barrier method of birth control example, either condom
with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap
(diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository,
and all men must also not donate sperm during the study and for 3 months after
receiving the last dose of any component of the treatment regimen. The exception to
this restriction is that if the participant's female partner is surgically sterile, a
second method of birth control is not required
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 therapies

- Participant has a history of malignancy (other than NHL) within 3 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 non-invasive 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 2 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 participants 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Box Hill
Recruitment hospital [3] 0 0
- Melbourne
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Box Hill
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Nebraska
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Belgium
State/province [13] 0 0
Brugge
Country [14] 0 0
Belgium
State/province [14] 0 0
Gent
Country [15] 0 0
France
State/province [15] 0 0
Lille
Country [16] 0 0
France
State/province [16] 0 0
Limoges Cedex
Country [17] 0 0
France
State/province [17] 0 0
Nantes Cedex 01
Country [18] 0 0
France
State/province [18] 0 0
Paris Cedex 10
Country [19] 0 0
France
State/province [19] 0 0
Pessac
Country [20] 0 0
France
State/province [20] 0 0
Pierre Benite
Country [21] 0 0
France
State/province [21] 0 0
Rouen Cedex
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Goyang-Si
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Seoul
Country [24] 0 0
Netherlands
State/province [24] 0 0
Amsterdam
Country [25] 0 0
Netherlands
State/province [25] 0 0
Rotterdam
Country [26] 0 0
Netherlands
State/province [26] 0 0
Utrecht
Country [27] 0 0
Turkey
State/province [27] 0 0
Ankara
Country [28] 0 0
Turkey
State/province [28] 0 0
Atakum
Country [29] 0 0
Turkey
State/province [29] 0 0
Istanbul
Country [30] 0 0
Turkey
State/province [30] 0 0
Kocaeli

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to assess overall response rate [ORR, including complete
response (CR) and partial response (PR)], of daratumumab in participants with non-Hodgkin's
lymphoma [a cancer of the lymph nodes (or tissues)-NHL] and 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 in participants with relapsed
or refractory mantle cell lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma.
Trial website
https://clinicaltrials.gov/show/NCT02413489
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02413489