E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma |
|
E.1.1.1 | Medical condition in easily understood language |
Relapsed or Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10012819 |
E.1.2 | Term | Diffuse large B-cell lymphomas |
E.1.2 | System Organ Class | 100000004851 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10016903 |
E.1.2 | Term | Follicle centre lymphomas, follicular grade I, II, III |
E.1.2 | System Organ Class | 100000004851 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10026798 |
E.1.2 | Term | Mantle cell lymphomas |
E.1.2 | System Organ Class | 100000004851 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
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 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
|
E.4 | Principal 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
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Number of Participants With Overall response rate (ORR) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Duration of response (DoR)
2. Progression Free Survival (PFS)
3. Overall survival (OS)
4. Time to response |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
France |
Korea, Republic of |
Netherlands |
Turkey |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the study for each NHL subtype is defined as 18 months after the last subject in the particular NHL subtype receives the first dose of daratumumab. After each NHL subtype completes the study, the sponsor will ensure that subjects who are currently on treatment and receiving benefit, as determined by the investigator, will continue to receive daratumumab. The end of the study is defined as the completion of all three NHL subtypes |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |