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: 10
Conditions
Sponsors
Janssen-Cilag International N.V.
Eligibility
Sex/Gender
All
Inclusion 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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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;Primary end point(s): Number of Participants With Overall response rate (ORR);Timepoint(s) of evaluation of this end point: Approximately 3.5 years | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
Australia, Belgium, France, Korea, Republic of, Netherlands, Turkey, United States
Contacts
Public ContactClinical Registry group
Janssen-Cilag International N.V.
Outcome results
None listed