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: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02413489
• Date of registration: 07/04/2015
• Prospective Registration: Yes
• Primary sponsor: Janssen Research & Development, LLC
• 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: September 2, 2015
• Target sample size: 36
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02413489
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

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

Contacts

• Name: Janssen Research & Development, LLC Clinical Trial
• Affiliation: Janssen Research & Development, LLC

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 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

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)



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Lymphoma, Follicular

Lymphoma, Large B-Cell, Diffuse

Lymphoma, Mantle-Cell

Intervention(s)

Drug: Daratumumab

Primary Outcome(s)

Overall Response Rate (ORR) [Time Frame: After the first dose until disease progression, withdrawal of consent from study participation, or the end of study (approximately 1.9 years)]

Secondary Outcome(s)

Duration of Response [Time Frame: Approximately 1.9 years]

Time to Response [Time Frame: Approximately 1.9 years]

Progression Free Survival (PFS) [Time Frame: Approximately 1.9 years]

Overall Survival (OS) [Time Frame: Approximately 1.9 years]

Secondary ID(s)

54767414LYM2001

2014-005299-26

CR106660

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 26/06/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02413489