Trial Outcomes & Findings for Bortezomib Plus Rituximab for EBV+ PTLD (NCT NCT01058239)

Last Updated: 2018-02-15

Results Overview

Overall response rate includes both complete and partial responses assessed by PET/CT following completion of therapy. Response was evaluated using the International Working Group criteria for lymphoma response. The complete list of criteria used to evaluate response is too long to be detailed in the allotted space here, but response is defined more generally as: * Complete Response (CR): Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. * Partial Response (PR): ≥ 50% decrease in the sum of the products of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

7 participants

Primary outcome timeframe

4 months

Results posted on

2018-02-15

Participant Flow

Participant milestones

Participant milestones
Measure	Rituximab Plus Bortezomib This is a single arm trial adding the new drug bortezomib to the standard drug rituximab bortezomib: Given intravenously on days 1, 4, 8 and 11 of every cycle rituximab: given intravenously on days 1, 8 and 15 of Cycle 1 and on Day 1 of subsequent cycles
Overall Study STARTED	7
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Bortezomib Plus Rituximab for EBV+ PTLD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab Plus Bortezomib n=7 Participants This is a single arm trial adding the new drug bortezomib to the standard drug rituximab bortezomib: Given intravenously on days 1, 4, 8 and 11 of every cycle rituximab: given intravenously on days 1, 8 and 15 of Cycle 1 and on Day 1 of subsequent cycles
Age, Continuous	67 years n=5 Participants
Age, Customized ≤ 50 years	1 Participants n=5 Participants
Age, Customized 51-60 years	0 Participants n=5 Participants
Age, Customized 61-70 years	3 Participants n=5 Participants
Age, Customized 71+ years	3 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants
ECOG Performance Status 0	4 Participants n=5 Participants
ECOG Performance Status 1	2 Participants n=5 Participants
ECOG Performance Status 2	1 Participants n=5 Participants
WHO Classification PTLD/polymorphic	2 Participants n=5 Participants
WHO Classification PTLD/monomorphic, DLBCL	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 months

Outcome measures

Outcome measures
Measure	Rituximab Plus Bortezomib n=7 Participants This is a single arm trial adding the new drug bortezomib to the standard drug rituximab bortezomib: Given intravenously on days 1, 4, 8 and 11 of every cycle rituximab: given intravenously on days 1, 8 and 15 of Cycle 1 and on Day 1 of subsequent cycles
Overall Response Rate	3 Participants

SECONDARY outcome

Timeframe: 4 Months

The number of participants with complete responses as assessed by PET/CT following completion of therapy. Response was evaluated using the International Working Group criteria for lymphoma response. Complete Response (CR): Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.

Outcome measures

Outcome measures
Measure	Rituximab Plus Bortezomib n=7 Participants This is a single arm trial adding the new drug bortezomib to the standard drug rituximab bortezomib: Given intravenously on days 1, 4, 8 and 11 of every cycle rituximab: given intravenously on days 1, 8 and 15 of Cycle 1 and on Day 1 of subsequent cycles
Complete Response Rate	3 Participants

SECONDARY outcome

Timeframe: six months

Percent of participants with progression free survival (alive without disease progression) six months after registration. Progression was evaluated using the International Working Group criteria for lymphoma response. \> Progressive Disease (PD) or Relapsed Disease (RD): 1. Appearance of any new lesion \> 1.5 cm in any axis during or at end of therapy. Increased Radiolabeled\[18F\]-2-fluoro-2-deoxy-D-glucose (FDG) uptake in a previously unaffected site will be considered PD/RD only after confirmation by other modalities. 2. ≥ 50% increase from nadir in the sum of the products of the largest diameters (SPD) of any previously involved node, or in a single involved node, or in the sizes of other lesions. 3. ≥ 50% increase in the longest diameter of any single previously identified node \> 1 cm in its short axis. 4. PET (positron emission tomography) positive prior to therapy: post-treatment PET should be positive unless lesion is too small to be detected with current PET sys

Outcome measures

Outcome measures
Measure	Rituximab Plus Bortezomib n=7 Participants This is a single arm trial adding the new drug bortezomib to the standard drug rituximab bortezomib: Given intravenously on days 1, 4, 8 and 11 of every cycle rituximab: given intravenously on days 1, 8 and 15 of Cycle 1 and on Day 1 of subsequent cycles
Six-Month Progression Free Survival	43 percentage of participants Interval 14.0 to 70.0

SECONDARY outcome

Timeframe: 6 months, 1 year

The percent of participants surviving at 6 months and 1 year.

Outcome measures

Outcome measures
Measure	Rituximab Plus Bortezomib n=7 Participants This is a single arm trial adding the new drug bortezomib to the standard drug rituximab bortezomib: Given intravenously on days 1, 4, 8 and 11 of every cycle rituximab: given intravenously on days 1, 8 and 15 of Cycle 1 and on Day 1 of subsequent cycles
Overall Survival 6 month	86 percentage of participants Interval 45.0 to 97.0
Overall Survival 12 Month	86 percentage of participants Interval 45.0 to 97.0

SECONDARY outcome

Timeframe: baseline, 21, 42, 63, 84 days (end of cycles 1, 2, 3, 4)

Population: Not all participants completed four cycles of treatment. The number of participants analyzed in each row differs according to the number of participants available for analysis at each time point.

The Mean epstein barr virus (EBV) viral load at the given time points.

Outcome measures

Outcome measures
Measure	Rituximab Plus Bortezomib n=7 Participants This is a single arm trial adding the new drug bortezomib to the standard drug rituximab bortezomib: Given intravenously on days 1, 4, 8 and 11 of every cycle rituximab: given intravenously on days 1, 8 and 15 of Cycle 1 and on Day 1 of subsequent cycles
Effects of Bortezomib/Rituximab on EBV Quantitative Viral Load Baseline	13.02 Log2[(viral copies/ milliliter blood)+1] Standard Deviation 3.39
Effects of Bortezomib/Rituximab on EBV Quantitative Viral Load End of Cycle 1 (21 days)	10.12 Log2[(viral copies/ milliliter blood)+1] Standard Deviation 3.18
Effects of Bortezomib/Rituximab on EBV Quantitative Viral Load End of Cycle 2 (42 days)	9.11 Log2[(viral copies/ milliliter blood)+1] Standard Deviation 6.19
Effects of Bortezomib/Rituximab on EBV Quantitative Viral Load End of Cycle 3 (63 days)	8.98 Log2[(viral copies/ milliliter blood)+1] Standard Deviation 2.29
Effects of Bortezomib/Rituximab on EBV Quantitative Viral Load End of Cycle 4 (84 days)	7.85 Log2[(viral copies/ milliliter blood)+1] Standard Deviation 0.34

SECONDARY outcome

Timeframe: 2 years

The toxicities experienced by participants that were deemed to be related to the study treatment. Data is shown as the number of participants that experienced any grade toxicity that was deemed to be related to treatment. Toxicities were assessed with the use of Common Toxicology Criteria for Adverse Events (CTCAE).

Outcome measures

Outcome measures
Measure	Rituximab Plus Bortezomib n=7 Participants This is a single arm trial adding the new drug bortezomib to the standard drug rituximab bortezomib: Given intravenously on days 1, 4, 8 and 11 of every cycle rituximab: given intravenously on days 1, 8 and 15 of Cycle 1 and on Day 1 of subsequent cycles
Treatment Related Toxicities Febrile Neutropenia	1 participants
Treatment Related Toxicities Leukocytosis	1 participants
Treatment Related Toxicities Lymph Node Pain	2 participants
Treatment Related Toxicities Abdominal Pain	1 participants
Treatment Related Toxicities Nausea	1 participants
Treatment Related Toxicities Neutrophil Count Decreased	2 participants
Treatment Related Toxicities Platelet Count Decreased	4 participants
Treatment Related Toxicities Alkalosis	1 participants
Treatment Related Toxicities Anorexia	1 participants
Treatment Related Toxicities Peripheral Sensory Neuropathy	2 participants

Adverse Events

Rituximab Plus Bortezomib

Serious events: 2 serious events

Other events: 7 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Rituximab Plus Bortezomib n=7 participants at risk This is a single arm trial adding the new drug bortezomib to the standard drug rituximab bortezomib: Given intravenously on days 1, 4, 8 and 11 of every cycle rituximab: given intravenously on days 1, 8 and 15 of Cycle 1 and on Day 1 of subsequent cycles
Investigations Platelet count decreased	14.3% 1/7 • Number of events 1 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Investigations Lymphocyte count decreased	14.3% 1/7 • Number of events 1 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Cardiac disorders Cardiac arrest	14.3% 1/7 • Number of events 1 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.

Other adverse events

Other adverse events
Measure	Rituximab Plus Bortezomib n=7 participants at risk This is a single arm trial adding the new drug bortezomib to the standard drug rituximab bortezomib: Given intravenously on days 1, 4, 8 and 11 of every cycle rituximab: given intravenously on days 1, 8 and 15 of Cycle 1 and on Day 1 of subsequent cycles
Blood and lymphatic system disorders Leukocytosis	28.6% 2/7 • Number of events 3 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Cardiac disorders Cardiac arrest	14.3% 1/7 • Number of events 1 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Gastrointestinal disorders Abdominal pain	14.3% 1/7 • Number of events 1 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Gastrointestinal disorders Diarrhea	14.3% 1/7 • Number of events 1 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Gastrointestinal disorders Nausea	14.3% 1/7 • Number of events 2 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Infections and infestations Catheter related infection	14.3% 1/7 • Number of events 1 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Infections and infestations Lung infection	14.3% 1/7 • Number of events 1 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Investigations Lymphocyte count decreased	57.1% 4/7 • Number of events 19 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Investigations Neutrophil count decreased	100.0% 7/7 • Number of events 38 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Investigations Platelet count decreased	100.0% 7/7 • Number of events 37 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Investigations Alkaline phosphatase increased	14.3% 1/7 • Number of events 4 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Metabolism and nutrition disorders Anorexia	14.3% 1/7 • Number of events 1 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Investigations Aspartate aminotransferase increased	14.3% 1/7 • Number of events 1 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Metabolism and nutrition disorders Hyperkalemia	14.3% 1/7 • Number of events 2 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Metabolism and nutrition disorders Hyponatremia	28.6% 2/7 • Number of events 6 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Nervous system disorders Peripheral motor neuropathy	100.0% 7/7 • Number of events 37 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Nervous system disorders Peripheral sensory neuropathy	100.0% 7/7 • Number of events 37 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.
Renal and urinary disorders Urinary tract pain	14.3% 1/7 • Number of events 1 • From baseline until the participant is off study, median duration of 14.9 months Adverse events were assessed with the use of regularly scheduled physical exams, laboratory tests, and patient self reports.

Additional Information

Jeremy Abramson, M.D

Massachusetts General Hospital

Phone: 617-724-4000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place