Trial Outcomes & Findings for An Efficacy and Safety Proof of Concept Study of Daratumumab in Relapsed/Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma (NCT NCT02413489)

Last Updated: 2025-02-04

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

36 participants

Primary outcome timeframe

After the first dose until disease progression, withdrawal of consent from study participation, or the end of study (approximately 1.9 years)

Results posted on

2025-02-04

Participant Flow

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).

Participant milestones

Participant milestones
Measure	Diffuse Large B-cell Lymphoma (DLBCL) 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.	Follicular Lymphoma (FL) 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.	Mantle Cell Lymphoma (MCL) 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.
Overall Study STARTED	15	16	5
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	15	16	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Diffuse Large B-cell Lymphoma (DLBCL) 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.	Follicular Lymphoma (FL) 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.	Mantle Cell Lymphoma (MCL) 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.
Overall Study Death	11	3	4
Overall Study Withdrawal by Subject	2	0	0
Overall Study Study Terminated By Sponsor	2	13	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Diffuse Large B-cell Lymphoma (DLBCL) n=15 Participants 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.	Follicular Lymphoma (FL) n=16 Participants 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.	Mantle Cell Lymphoma (MCL) n=5 Participants 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 n=36 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	9 Participants n=7 Participants	4 Participants n=5 Participants	18 Participants n=4 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants	7 Participants n=7 Participants	1 Participants n=5 Participants	18 Participants n=4 Participants
Age, Continuous	66.7 years STANDARD_DEVIATION 11.88 • n=5 Participants	62.3 years STANDARD_DEVIATION 9.77 • n=7 Participants	59.8 years STANDARD_DEVIATION 6.69 • n=5 Participants	63.8 years STANDARD_DEVIATION 10.45 • n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	5 Participants n=7 Participants	0 Participants n=5 Participants	11 Participants n=4 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	11 Participants n=7 Participants	5 Participants n=5 Participants	25 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	15 Participants n=7 Participants	2 Participants n=5 Participants	29 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Asian	4 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized White	7 Participants n=5 Participants	13 Participants n=7 Participants	2 Participants n=5 Participants	22 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment Australia	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment Belgium	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment France	4 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	6 Participants n=4 Participants
Region of Enrollment Netherlands	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Region of Enrollment Republic of Korea	4 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	6 Participants n=4 Participants
Region of Enrollment Turkey	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Region of Enrollment United States	1 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
CD38 expression value	76.3 Percentage of CD38 expression STANDARD_DEVIATION 18.07 • n=5 Participants	70.3 Percentage of CD38 expression STANDARD_DEVIATION 16.78 • n=7 Participants	64 Percentage of CD38 expression STANDARD_DEVIATION 8.22 • n=5 Participants	71.9 Percentage of CD38 expression STANDARD_DEVIATION 16.66 • n=4 Participants

PRIMARY outcome

Timeframe: After the first dose until disease progression, withdrawal of consent from study participation, or the end of study (approximately 1.9 years)

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

Outcome measures

Outcome measures
Measure	Diffuse Large B-cell Lymphoma (DLBCL) n=15 Participants 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.	Follicular Lymphoma (FL) n=16 Participants 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.	Mantle Cell Lymphoma (MCL) n=5 Participants 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.
Overall Response Rate (ORR)	6.7 Percentage of participants Interval 0.2 to 31.9	12.5 Percentage of participants Interval 1.6 to 38.3	0 Percentage of participants Confidence interval was not estimable as no participants had response.

SECONDARY outcome

Timeframe: Approximately 1.9 years

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Diffuse Large B-cell Lymphoma (DLBCL) n=1 Participants 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.	Follicular Lymphoma (FL) n=2 Participants 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.	Mantle Cell Lymphoma (MCL) 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.
Duration of Response Participant 1	1.6 Months	0.7 Months	—
Duration of Response Participant 2	NA Months Only 1 participant achieved response in DLBCL group.	7.4 Months	—

SECONDARY outcome

Timeframe: Approximately 1.9 years

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

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

Outcome measures

Outcome measures
Measure	Diffuse Large B-cell Lymphoma (DLBCL) n=15 Participants 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.	Follicular Lymphoma (FL) n=16 Participants 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.	Mantle Cell Lymphoma (MCL) n=5 Participants 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.
Progression Free Survival (PFS)	1.2 Months Interval 0.6 to 1.7	3.3 Months Interval 1.9 to 3.8	1.3 Months Interval 0.5 to 1.9

SECONDARY outcome

Timeframe: Approximately 1.9 years

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

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

Outcome measures

Outcome measures
Measure	Diffuse Large B-cell Lymphoma (DLBCL) n=15 Participants 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.	Follicular Lymphoma (FL) n=16 Participants 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.	Mantle Cell Lymphoma (MCL) n=5 Participants 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.
Overall Survival (OS)	4.9 Months Interval 2.1 to 9.0	17.2 Months Interval 15.0 to NA indicates upper limit of Confidence Interval was not estimable due to less number of participants with events.	4.8 Months Interval 1.7 to Upper limit of CI could not be estimated due to less number of participants analyzed.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Diffuse Large B-cell Lymphoma (DLBCL) n=1 Participants 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.	Follicular Lymphoma (FL) n=2 Participants 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.	Mantle Cell Lymphoma (MCL) 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.
Time to Response Participant 1	1.9 Months	2.3 Months	—
Time to Response Participant 2	NA Months Only 1 participant achieved response in DLBCL group.	1.9 Months	—

Adverse Events

Diffuse Large B-cell Lymphoma (DLBCL)

Serious events: 6 serious events

Other events: 15 other events

Deaths: 11 deaths

Follicular Lymphoma (FL)

Serious events: 6 serious events

Other events: 16 other events

Deaths: 3 deaths

Mantle Cell Lymphoma (MCL)

Serious events: 3 serious events

Other events: 5 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Diffuse Large B-cell Lymphoma (DLBCL) n=15 participants at risk 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.	Follicular Lymphoma (FL) n=16 participants at risk 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.	Mantle Cell Lymphoma (MCL) n=5 participants at risk 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.
Blood and lymphatic system disorders Febrile Neutropenia	0.00% 0/15 • Up to 1.9 years 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.	6.2% 1/16 • Up to 1.9 years 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.	20.0% 1/5 • Up to 1.9 years 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.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/15 • Up to 1.9 years 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.	6.2% 1/16 • Up to 1.9 years 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.	0.00% 0/5 • Up to 1.9 years 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.
Blood and lymphatic system disorders Thrombocytopenia	6.7% 1/15 • Up to 1.9 years 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.	0.00% 0/16 • Up to 1.9 years 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.	0.00% 0/5 • Up to 1.9 years 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.
Gastrointestinal disorders Abdominal Pain Lower	6.7% 1/15 • Up to 1.9 years 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.	0.00% 0/16 • Up to 1.9 years 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.	0.00% 0/5 • Up to 1.9 years 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.
General disorders General Physical Health Deterioration	6.7% 1/15 • Up to 1.9 years 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.	0.00% 0/16 • Up to 1.9 years 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.	20.0% 1/5 • Up to 1.9 years 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.
General disorders Pyrexia	0.00% 0/15 • Up to 1.9 years 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.	0.00% 0/16 • Up to 1.9 years 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.	40.0% 2/5 • Up to 1.9 years 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.
Infections and infestations Pneumonia	6.7% 1/15 • Up to 1.9 years 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.	6.2% 1/16 • Up to 1.9 years 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.	0.00% 0/5 • Up to 1.9 years 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.
Infections and infestations Pneumonia Cytomegaloviral	0.00% 0/15 • Up to 1.9 years 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.	6.2% 1/16 • Up to 1.9 years 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.	0.00% 0/5 • Up to 1.9 years 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.
Infections and infestations Urinary Tract Infection	0.00% 0/15 • Up to 1.9 years 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.	6.2% 1/16 • Up to 1.9 years 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.	0.00% 0/5 • Up to 1.9 years 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.
Injury, poisoning and procedural complications Spinal Fracture	0.00% 0/15 • Up to 1.9 years 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.	6.2% 1/16 • Up to 1.9 years 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.	0.00% 0/5 • Up to 1.9 years 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.
Metabolism and nutrition disorders Decreased Appetite	6.7% 1/15 • Up to 1.9 years 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.	0.00% 0/16 • Up to 1.9 years 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.	0.00% 0/5 • Up to 1.9 years 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.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	6.7% 1/15 • Up to 1.9 years 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.	0.00% 0/16 • Up to 1.9 years 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.	0.00% 0/5 • Up to 1.9 years 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse Large B-Cell Lymphoma	0.00% 0/15 • Up to 1.9 years 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.	6.2% 1/16 • Up to 1.9 years 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.	0.00% 0/5 • Up to 1.9 years 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.
Renal and urinary disorders Acute Kidney Injury	6.7% 1/15 • Up to 1.9 years 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.	0.00% 0/16 • Up to 1.9 years 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.	0.00% 0/5 • Up to 1.9 years 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.
Renal and urinary disorders Chronic Kidney Disease	6.7% 1/15 • Up to 1.9 years 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.	0.00% 0/16 • Up to 1.9 years 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.	0.00% 0/5 • Up to 1.9 years 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.