Trial Outcomes & Findings for Everolimus Plus Rituximab for Relapsed/Refractory Diffuse Large B Cell Lymphoma (NCT NCT00869999)

Last Updated: 2014-10-27

Results Overview

Complete response plus partial response after 6 cycles. Response rate will be evaluated by using the modified Cheson criteria for lymphoma response. Complete response requires all of the following: 1) PET positive prior to therapy: mass of any size permitted if PET negative. Variable FDG-avid or PET negative prior to therapy: regression to normal size on CT (\</= 1.5cm in their greatest transverse diameter for nodes \>/= 1.5 cm before therapy) 2) Spleen (if enlarged before therapy) must have regressed in size and must not be palpable, 3) If bone marrow is known to be involved, repeat biopsy documents clearance. Partial response requires 1) \>/= 50% decrease in SPD, 2) No new sites of disease or increase in the size of other nodes, liver or spleen, 3) Splenic and hepatic nodules must regress by at least 50% in SPD

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

26 participants

Primary outcome timeframe

Assessed at the conclusion of cycle 2, cycle 4 and cycle 6

Results posted on

2014-10-27

Participant Flow

Patients were recruited in the lymphoma programs of the Massachusetts General Hospital Cancer Center, Dana-Farber Cancer Institute and Beth-Israel Deaconess Medical Center

Participant milestones

Participant milestones
Measure	Everolimus-Rituximab All patients received treatment with everolimus-rituximab on this single am study. Everloimus was administered at a dose of 10mg by mouth once daily on days 1-28 of a 28-day cycle. Rituximab was administered at a dose of 375 mg/m3 intravenously weekly for four doses during cycle 1, and then on day 1 of cycles 2-6. After cycle 6, patients could receive an additional 6 months of everolimus monotherapy in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	26
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Everolimus-Rituximab All patients received treatment with everolimus-rituximab on this single am study. Everloimus was administered at a dose of 10mg by mouth once daily on days 1-28 of a 28-day cycle. Rituximab was administered at a dose of 375 mg/m3 intravenously weekly for four doses during cycle 1, and then on day 1 of cycles 2-6. After cycle 6, patients could receive an additional 6 months of everolimus monotherapy in the absence of disease progression or unacceptable toxicity.
Overall Study Withdrawal by Subject	1
Overall Study removed prior to starting therapy	1

Baseline Characteristics

Everolimus Plus Rituximab for Relapsed/Refractory Diffuse Large B Cell Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Arm n=25 Participants All patients received treatment with everolimus-rituximab on this single am study
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants
Age, Categorical >=65 years	13 Participants n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed at the conclusion of cycle 2, cycle 4 and cycle 6

Outcome measures

Outcome measures
Measure	Everolimus/Rituximab n=24 Participants All patients received treatment with everolimus-rituximab on this single am study. Everloimus was administered at a dose of 10mg by mouth once daily on days 1-28 of a 28-day cycle. Rituximab was administered at a dose of 375 mg/m3 intravenously weekly for four doses during cycle 1, and then on day 1 of cycles 2-6. After cycle 6, patients could receive an additional 6 months of everolimus monotherapy in the absence of disease progression or unacceptable toxicity.
Overall Response Rate	38 percentage of participants Interval 21.0 to 56.0

SECONDARY outcome

Timeframe: 2 years

Duration of overall response is measured from the time measurement criteria are met for complete response or partial response until the first date that recurrent or progressive disease is objectively documented.

Outcome measures

Outcome measures
Measure	Everolimus/Rituximab n=24 Participants All patients received treatment with everolimus-rituximab on this single am study. Everloimus was administered at a dose of 10mg by mouth once daily on days 1-28 of a 28-day cycle. Rituximab was administered at a dose of 375 mg/m3 intravenously weekly for four doses during cycle 1, and then on day 1 of cycles 2-6. After cycle 6, patients could receive an additional 6 months of everolimus monotherapy in the absence of disease progression or unacceptable toxicity.
Duration of Overall Response	8.1 months Interval 4.9 to 16.3

SECONDARY outcome

Timeframe: 2 years

Progression-free survival is defined as the duration of time from start of treatment to time of documentation of progression or death

Outcome measures

Outcome measures
Measure	Everolimus/Rituximab n=24 Participants All patients received treatment with everolimus-rituximab on this single am study. Everloimus was administered at a dose of 10mg by mouth once daily on days 1-28 of a 28-day cycle. Rituximab was administered at a dose of 375 mg/m3 intravenously weekly for four doses during cycle 1, and then on day 1 of cycles 2-6. After cycle 6, patients could receive an additional 6 months of everolimus monotherapy in the absence of disease progression or unacceptable toxicity.
Progression-free Survival	2.9 months Interval 1.8 to 3.8

Adverse Events

Everolimus/Rituximab

Serious events: 6 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Everolimus/Rituximab n=24 participants at risk All patients received treatment with everolimus-rituximab on this single am study. Everloimus was administered at a dose of 10mg by mouth once daily on days 1-28 of a 28-day cycle. Rituximab was administered at a dose of 375 mg/m3 intravenously weekly for four doses during cycle 1, and then on day 1 of cycles 2-6. After cycle 6, patients could receive an additional 6 months of everolimus monotherapy in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Leukocytosis	4.2% 1/24 • Number of events 1
Gastrointestinal disorders Viral hepatitis	4.2% 1/24 • Number of events 1
Metabolism and nutrition disorders Hyperuricemia	4.2% 1/24 • Number of events 1
Blood and lymphatic system disorders Neutropenia	12.5% 3/24 • Number of events 3

Other adverse events

Other adverse events
Measure	Everolimus/Rituximab n=24 participants at risk All patients received treatment with everolimus-rituximab on this single am study. Everloimus was administered at a dose of 10mg by mouth once daily on days 1-28 of a 28-day cycle. Rituximab was administered at a dose of 375 mg/m3 intravenously weekly for four doses during cycle 1, and then on day 1 of cycles 2-6. After cycle 6, patients could receive an additional 6 months of everolimus monotherapy in the absence of disease progression or unacceptable toxicity.
General disorders Fatigue	33.3% 8/24
General disorders Anorexia	12.5% 3/24
General disorders Rash	12.5% 3/24
Blood and lymphatic system disorders Neutropenia	37.5% 9/24
Blood and lymphatic system disorders Anemia	41.7% 10/24
Blood and lymphatic system disorders Thrombocytopenia	45.8% 11/24
Blood and lymphatic system disorders Leukocytosis	33.3% 8/24
Metabolism and nutrition disorders Hyperglycemia	25.0% 6/24
Metabolism and nutrition disorders Hypertriglyceridemia	25.0% 6/24
Infections and infestations Infection with < grade 3 neutropenia	16.7% 4/24
Respiratory, thoracic and mediastinal disorders Dyspnea	8.3% 2/24

Additional Information

Jeffrey Barnes, MD

Massachusetts General Hospital Cancer Center

Phone: 617-724-4000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place