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

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02413489
• Collaborator: (none)
• Enrollment: 36
• Locations: 35
• Arm: 1
• Actual Duration (Months): 21
• Patients Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular	Drug: Daratumumab	Phase 2

Detailed Description

This is an open label (everyone knows the study intervention), 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. The study will have three phases. Screening phase, treatment phase, follow-up phase. Participants will receive daratumumab (16 milligram per kilogram [mg/kg]) as intravenous infusion approximately 3.5 years. Participants will primarily be assessed for overall response rate. Safety will be monitored throughout the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official 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
• Actual Study Start Date: Sep 2, 2015
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Jun 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: 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.

Outcome Measures

Primary Outcome Measures

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

   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.

Secondary Outcome Measures

1. Duration of Response [Approximately 1.9 years]

   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.

2. Progression Free Survival (PFS) [Approximately 1.9 years]

   PFS was defined as the duration from the date of the first daratumumab dose to the date of progression or death, whichever comes first.

3. Overall Survival (OS) [Approximately 1.9 years]

   Overall survival was defined as the duration from the date of the first daratumumab dose to the date of death.

4. Time to Response [Approximately 1.9 years]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Duarte	California	United States
2		Fountain Valley	California	United States
3		Jacksonville	Florida	United States
4		Pembroke Pines	Florida	United States
5		Atlanta	Georgia	United States
6		Chicago	Illinois	United States
7		Louisville	Kentucky	United States
8		Baltimore	Maryland	United States
9		Rochester	Minnesota	United States
10		Omaha	Nebraska	United States
11		New Brunswick	New Jersey	United States
12		Pittsburgh	Pennsylvania	United States
13		Houston	Texas	United States
14		Seattle	Washington	United States
15		Adelaide		Australia
16		Box Hill		Australia
17		Melbourne		Australia
18		Brugge		Belgium
19		Gent		Belgium
20		Lille		France
21		Limoges Cedex		France
22		Nantes Cedex 01		France
23		Paris Cedex 10		France
24		Pessac		France
25		Pierre Benite		France
26		Rouen Cedex		France
27		Goyang-Si		Korea, Republic of
28		Seoul		Korea, Republic of
29		Amsterdam		Netherlands
30		Rotterdam		Netherlands
31		Utrecht		Netherlands
32		Ankara		Turkey
33		Atakum		Turkey
34		Istanbul		Turkey
35		Kocaeli		Turkey

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

• Study Protocol - Jan 19, 2016
• Statistical Analysis Plan - May 16, 2017

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT02413489
• Other Study ID Numbers: CR106660; 54767414LYM2001; 2014-005299-26
• First Posted: Apr 10, 2015
• Last Update Posted: Jun 26, 2018
• Last Verified: May 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Janssen Research & Development, LLC: Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Daratumumab
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Daratumumab

Study Results

Participant Flow

Pre-assignment Detail	In total 36 participants were treated (15 participants in the diffuse large B-cell lymphoma [DLBCL] cohort, 16 participants in the follicular lymphoma [FL] cohort, and 5 participants in the mantle cell lymphoma [MCL] cohort).

Arm/Group Title	Diffuse Large B-cell Lymphoma (DLBCL)	Follicular Lymphoma (FL)	Mantle Cell Lymphoma (MCL)
Arm/Group Description	Participants received 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.	Participants received daratumumab 16 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.	Participants received daratumumab 16 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.
Period Title: Overall Study
STARTED	15	16	5
COMPLETED	0	0	0
NOT COMPLETED	15	16	5

Baseline Characteristics

Arm/Group Title	Diffuse Large B-cell Lymphoma (DLBCL)	Follicular Lymphoma (FL)	Mantle Cell Lymphoma (MCL)	Total
Arm/Group Description	Participants received 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.	Participants received daratumumab 16 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.	Participants received daratumumab 16 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.	Total of all reporting groups
Overall Participants	15	16	5	36
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	5 33.3%	9 56.3%	4 80%	18 50%
>=65 years	10 66.7%	7 43.8%	1 20%	18 50%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.7 (11.88)	62.3 (9.77)	59.8 (6.69)	63.8 (10.45)
Sex: Female, Male (Count of Participants)
Female	6 40%	5 31.3%	0 0%	11 30.6%
Male	9 60%	11 68.8%	5 100%	25 69.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 6.3%	2 40%	3 8.3%
Not Hispanic or Latino	12 80%	15 93.8%	2 40%	29 80.6%
Unknown or Not Reported	3 20%	0 0%	1 20%	4 11.1%
Race/Ethnicity, Customized (Count of Participants)
Asian	4 26.7%	2 12.5%	0 0%	6 16.7%
White	7 46.7%	13 81.3%	2 40%	22 61.1%
Unknown	1 6.7%	0 0%	0 0%	1 2.8%
Not Reported	3 20%	1 6.3%	1 20%	5 13.9%
Other	0 0%	0 0%	2 40%	2 5.6%
Region of Enrollment (Count of Participants)
Australia	0 0%	2 12.5%	0 0%	2 5.6%
Belgium	2 13.3%	0 0%	0 0%	2 5.6%
France	4 26.7%	2 12.5%	0 0%	6 16.7%
Netherlands	2 13.3%	3 18.8%	2 40%	7 19.4%
Republic of Korea	4 26.7%	2 12.5%	0 0%	6 16.7%
Turkey	2 13.3%	2 12.5%	1 20%	5 13.9%
United States	1 6.7%	5 31.3%	2 40%	8 22.2%
CD38 expression value (Percentage of CD38 expression) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of CD38 expression]	76.3 (18.07)	70.3 (16.78)	64 (8.22)	71.9 (16.66)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis population was all participants that were treated with daratumumab.

Arm/Group Title	Diffuse Large B-cell Lymphoma (DLBCL)	Follicular Lymphoma (FL)	Mantle Cell Lymphoma (MCL)
Arm/Group Description	Participants received 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.	Participants received daratumumab 16 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.	Participants received daratumumab 16 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.
Measure Participants	15	16	5
Number (95% Confidence Interval) [Percentage of participants]	6.7 44.7%	12.5 78.1%	0 0%

2. Secondary Outcome

Title	Duration of Response
Description	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.
Time Frame	Approximately 1.9 years

Outcome Measure Data

Analysis Population Description

The analysis population was all participants that were treated with daratumumab and who achieved overall response There was insufficient data to perform Kaplan Meier analysis, therefore individual data for each evaluable participant was reported.

Arm/Group Title	Diffuse Large B-cell Lymphoma (DLBCL)	Follicular Lymphoma (FL)	Mantle Cell Lymphoma (MCL)
Arm/Group Description	Participants received 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.	Participants received daratumumab 16 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.	Participants received daratumumab 16 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.
Measure Participants	1	2	0
Participant 1	1.6	0.7
Participant 2	NA	7.4

3. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS was defined as the duration from the date of the first daratumumab dose to the date of progression or death, whichever comes first.
Time Frame	Approximately 1.9 years

Outcome Measure Data

Analysis Population Description

The analysis population was all participants that were treated with daratumumab.

Arm/Group Title	Diffuse Large B-cell Lymphoma (DLBCL)	Follicular Lymphoma (FL)	Mantle Cell Lymphoma (MCL)
Arm/Group Description	Participants received 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.	Participants received daratumumab 16 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.	Participants received daratumumab 16 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.
Measure Participants	15	16	5
Median (95% Confidence Interval) [Months]	1.2	3.3	1.3

4. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival was defined as the duration from the date of the first daratumumab dose to the date of death.
Time Frame	Approximately 1.9 years

Outcome Measure Data

Analysis Population Description

The analysis population was all participants that were treated with daratumumab.

Arm/Group Title	Diffuse Large B-cell Lymphoma (DLBCL)	Follicular Lymphoma (FL)	Mantle Cell Lymphoma (MCL)
Arm/Group Description	Participants received 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.	Participants received daratumumab 16 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.	Participants received daratumumab 16 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.
Measure Participants	15	16	5
Median (95% Confidence Interval) [Months]	4.9	17.2	4.8

5. Secondary Outcome

Title	Time to Response
Description	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.
Time Frame	Approximately 1.9 years

Outcome Measure Data

Analysis Population Description

The analysis population was all participants that were treated with daratumumab and who achieved overall response There was insufficient data to perform Kaplan Meier analysis, therefore individual data for each evaluable participant was reported.

Arm/Group Title	Diffuse Large B-cell Lymphoma (DLBCL)	Follicular Lymphoma (FL)	Mantle Cell Lymphoma (MCL)
Arm/Group Description	Participants received 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.	Participants received daratumumab 16 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.	Participants received daratumumab 16 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.
Measure Participants	1	2	0
Participant 1	1.9	2.3
Participant 2	NA	1.9

Adverse Events

Time Frame	Up to 1.9 years
Adverse Event Reporting Description	Analysis set included all participants who received at least 1 dose of study treatment and contributed any safety data after the start of study treatment.
Arm/Group Title	Diffuse Large B-cell Lymphoma (DLBCL)		Follicular Lymphoma (FL)		Mantle Cell Lymphoma (MCL)
Arm/Group Description	Participants received 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.		Participants received daratumumab 16 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.		Participants received daratumumab 16 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.
All Cause Mortality
	Diffuse Large B-cell Lymphoma (DLBCL)		Follicular Lymphoma (FL)		Mantle Cell Lymphoma (MCL)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/15 (73.3%)		3/16 (18.8%)		4/5 (80%)
Serious Adverse Events
	Diffuse Large B-cell Lymphoma (DLBCL)		Follicular Lymphoma (FL)		Mantle Cell Lymphoma (MCL)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/15 (40%)		6/16 (37.5%)		3/5 (60%)
Blood and lymphatic system disorders
Febrile Neutropenia	0/15 (0%)		1/16 (6.3%)		1/5 (20%)
Lymphadenopathy	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Thrombocytopenia	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Gastrointestinal disorders
Abdominal Pain Lower	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
General disorders
General Physical Health Deterioration	1/15 (6.7%)		0/16 (0%)		1/5 (20%)
Pyrexia	0/15 (0%)		0/16 (0%)		2/5 (40%)
Infections and infestations
Pneumonia	1/15 (6.7%)		1/16 (6.3%)		0/5 (0%)
Pneumonia Cytomegaloviral	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Urinary Tract Infection	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Injury, poisoning and procedural complications
Spinal Fracture	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Metabolism and nutrition disorders
Decreased Appetite	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Diffuse Large B-Cell Lymphoma	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Renal and urinary disorders
Acute Kidney Injury	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Chronic Kidney Disease	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Diffuse Large B-cell Lymphoma (DLBCL)		Follicular Lymphoma (FL)		Mantle Cell Lymphoma (MCL)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/15 (100%)		16/16 (100%)		5/5 (100%)
Blood and lymphatic system disorders
Anaemia	1/15 (6.7%)		5/16 (31.3%)		1/5 (20%)
Leukopenia	1/15 (6.7%)		1/16 (6.3%)		0/5 (0%)
Lymph Node Pain	2/15 (13.3%)		2/16 (12.5%)		0/5 (0%)
Lymphadenopathy	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Lymphocytosis	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Lymphopenia	0/15 (0%)		2/16 (12.5%)		0/5 (0%)
Neutropenia	1/15 (6.7%)		1/16 (6.3%)		1/5 (20%)
Thrombocytopenia	3/15 (20%)		3/16 (18.8%)		1/5 (20%)
Cardiac disorders
Sinus Bradycardia	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Ear and labyrinth disorders
Ear Pain	0/15 (0%)		2/16 (12.5%)		0/5 (0%)
Eye disorders
Diplopia	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Erythema of Eyelid	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Eyelid Oedema	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Ocular Hyperaemia	0/15 (0%)		1/16 (6.3%)		1/5 (20%)
Visual Acuity Reduced	0/15 (0%)		0/16 (0%)		1/5 (20%)
Gastrointestinal disorders
Abdominal Discomfort	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Abdominal Pain	2/15 (13.3%)		5/16 (31.3%)		1/5 (20%)
Abdominal Pain Lower	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Abdominal Pain Upper	1/15 (6.7%)		1/16 (6.3%)		0/5 (0%)
Anal Incontinence	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Constipation	2/15 (13.3%)		2/16 (12.5%)		1/5 (20%)
Dental Caries	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Diarrhoea	1/15 (6.7%)		2/16 (12.5%)		0/5 (0%)
Dry Mouth	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Gastrooesophageal Reflux Disease	0/15 (0%)		0/16 (0%)		1/5 (20%)
Nausea	5/15 (33.3%)		1/16 (6.3%)		2/5 (40%)
Paraesthesia Oral	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Swollen Tongue	0/15 (0%)		0/16 (0%)		1/5 (20%)
Vomiting	4/15 (26.7%)		0/16 (0%)		1/5 (20%)
General disorders
Asthenia	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Catheter Site Erythema	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Catheter Site Inflammation	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Chest Discomfort	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Chills	2/15 (13.3%)		1/16 (6.3%)		1/5 (20%)
Fatigue	4/15 (26.7%)		3/16 (18.8%)		1/5 (20%)
General Physical Health Deterioration	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Influenza Like Illness	0/15 (0%)		2/16 (12.5%)		0/5 (0%)
Malaise	3/15 (20%)		1/16 (6.3%)		0/5 (0%)
Non-Cardiac Chest Pain	0/15 (0%)		1/16 (6.3%)		1/5 (20%)
Oedema Peripheral	1/15 (6.7%)		2/16 (12.5%)		1/5 (20%)
Pain	1/15 (6.7%)		1/16 (6.3%)		0/5 (0%)
Pyrexia	2/15 (13.3%)		4/16 (25%)		1/5 (20%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/15 (0%)		0/16 (0%)		1/5 (20%)
Infections and infestations
Cellulitis	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Fungal Skin Infection	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Gastroenteritis	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Genital Herpes	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Groin Infection	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Herpes Zoster	0/15 (0%)		1/16 (6.3%)		1/5 (20%)
Lower Respiratory Tract Infection	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Nasopharyngitis	1/15 (6.7%)		1/16 (6.3%)		1/5 (20%)
Pneumonia	0/15 (0%)		0/16 (0%)		1/5 (20%)
Rhinitis	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Sinusitis	0/15 (0%)		2/16 (12.5%)		0/5 (0%)
Upper Respiratory Tract Infection	1/15 (6.7%)		3/16 (18.8%)		0/5 (0%)
Urinary Tract Infection	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Viral Upper Respiratory Tract Infection	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Injury, poisoning and procedural complications
Contusion	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Hip Fracture	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Procedural Pain	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Skin Abrasion	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Investigations
Alanine Aminotransferase Increased	1/15 (6.7%)		0/16 (0%)		1/5 (20%)
Aspartate Aminotransferase Increased	2/15 (13.3%)		0/16 (0%)		0/5 (0%)
C-Reactive Protein Increased	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Cytomegalovirus Test Positive	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Oxygen Saturation Decreased	1/15 (6.7%)		1/16 (6.3%)		0/5 (0%)
Prostatic Specific Antigen Increased	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Weight Decreased	3/15 (20%)		2/16 (12.5%)		0/5 (0%)
Weight Increased	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Metabolism and nutrition disorders
Decreased Appetite	1/15 (6.7%)		1/16 (6.3%)		0/5 (0%)
Hyperglycaemia	0/15 (0%)		0/16 (0%)		1/5 (20%)
Hypertriglyceridaemia	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Hyperuricaemia	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Hypoalbuminaemia	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Hypokalaemia	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Hyponatraemia	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Vitamin B12 Deficiency	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/15 (0%)		2/16 (12.5%)		0/5 (0%)
Back Pain	1/15 (6.7%)		4/16 (25%)		1/5 (20%)
Flank Pain	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Mobility Decreased	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Muscle Spasms	0/15 (0%)		1/16 (6.3%)		2/5 (40%)
Musculoskeletal Chest Pain	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Musculoskeletal Pain	2/15 (13.3%)		1/16 (6.3%)		0/5 (0%)
Myalgia	1/15 (6.7%)		2/16 (12.5%)		0/5 (0%)
Pain in Extremity	0/15 (0%)		3/16 (18.8%)		1/5 (20%)
Pain in Jaw	0/15 (0%)		0/16 (0%)		1/5 (20%)
Peripheral Arthritis	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour Pain	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Nervous system disorders
Dizziness	1/15 (6.7%)		1/16 (6.3%)		1/5 (20%)
Dysarthria	0/15 (0%)		0/16 (0%)		1/5 (20%)
Headache	0/15 (0%)		5/16 (31.3%)		1/5 (20%)
Nerve Compression	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Neuralgia	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Paraesthesia	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Peripheral Sensory Neuropathy	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Post Herpetic Neuralgia	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Sensory Disturbance	0/15 (0%)		0/16 (0%)		1/5 (20%)
Somnolence	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Product Issues
Thrombosis in Device	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Psychiatric disorders
Anxiety	2/15 (13.3%)		0/16 (0%)		0/5 (0%)
Delirium	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Depressed Mood	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Insomnia	3/15 (20%)		2/16 (12.5%)		1/5 (20%)
Renal and urinary disorders
Chronic Kidney Disease	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Haematuria	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Urinary Tract Obstruction	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Urine Flow Decreased	0/15 (0%)		0/16 (0%)		1/5 (20%)
Respiratory, thoracic and mediastinal disorders
Cough	7/15 (46.7%)		6/16 (37.5%)		4/5 (80%)
Dysphonia	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Dyspnoea	1/15 (6.7%)		2/16 (12.5%)		2/5 (40%)
Hiccups	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Hypoxia	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Laryngeal Oedema	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Nasal Congestion	0/15 (0%)		3/16 (18.8%)		1/5 (20%)
Oropharyngeal Discomfort	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Oropharyngeal Pain	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Pharyngeal Oedema	0/15 (0%)		0/16 (0%)		1/5 (20%)
Pleural Effusion	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Productive Cough	0/15 (0%)		2/16 (12.5%)		0/5 (0%)
Rales	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Respiratory Failure	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Rhinorrhoea	0/15 (0%)		2/16 (12.5%)		0/5 (0%)
Sinus Congestion	0/15 (0%)		0/16 (0%)		1/5 (20%)
Sneezing	0/15 (0%)		2/16 (12.5%)		0/5 (0%)
Throat Irritation	0/15 (0%)		2/16 (12.5%)		2/5 (40%)
Upper-Airway Cough Syndrome	0/15 (0%)		0/16 (0%)		1/5 (20%)
Wheezing	0/15 (0%)		0/16 (0%)		1/5 (20%)
Skin and subcutaneous tissue disorders
Acne	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Blood Blister	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Eczema	1/15 (6.7%)		0/16 (0%)		0/5 (0%)
Erythema	0/15 (0%)		0/16 (0%)		1/5 (20%)
Night Sweats	1/15 (6.7%)		2/16 (12.5%)		0/5 (0%)
Pain of Skin	1/15 (6.7%)		2/16 (12.5%)		0/5 (0%)
Pruritus	1/15 (6.7%)		0/16 (0%)		1/5 (20%)
Rash	1/15 (6.7%)		1/16 (6.3%)		0/5 (0%)
Skin Burning Sensation	0/15 (0%)		1/16 (6.3%)		0/5 (0%)
Urticaria	1/15 (6.7%)		3/16 (18.8%)		0/5 (0%)
Vascular disorders
Flushing	0/15 (0%)		2/16 (12.5%)		1/5 (20%)
Hot Flush	0/15 (0%)		0/16 (0%)		1/5 (20%)
Hypertension	2/15 (13.3%)		3/16 (18.8%)		0/5 (0%)
Hypotension	1/15 (6.7%)		1/16 (6.3%)		0/5 (0%)

Limitations/Caveats

The study was terminated due to 2 non-Hodgkin's lymphoma (NHL) sub types (DLBCL and FL cohorts) meeting the futility criteria defined in the protocol and the MCL cohort not having adequate recruitment.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.