Trial Outcomes & Findings for Maintenance Rituximab With mTor Inhibition After High-dose Consolidative Therapy in Lymphoma (NCT NCT01665768)

NCT ID: NCT01665768

Last Updated: 2021-10-26

Results Overview

Number of participants who did not experience at least one grade 3-4 adverse event by CTCAE 4.0.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 56 participants
• Primary outcome timeframe: Up to 3 years
• Results posted on: 2021-10-26

Participant Flow

7 participants were screen failures.

Participant milestones

Measure	Everolimus and Rituximab Everolimus daily for one year and IV rituximab four times during that year. Everolimus: The initial dose of everolimus will be 2.5mg orally daily for a total of one year to maintain a target trough concentration between 3-15 ng/mL. Previously the study allowed for starting doses of 5mg and 10mg; the starting dose was reduced in subsequent amendments due to a high incidence of dose reductions. 2.5mg was the most frequent daily dose for all patients, and the entire population was analyzed as one arm. Rituximab: 375mg/m2 day +1 and then every 90 days for 1 year (a total of 4 infusions)
Overall Study STARTED	49
Overall Study COMPLETED	26
Overall Study NOT COMPLETED	23

Reasons for withdrawal

Measure	Everolimus and Rituximab Everolimus daily for one year and IV rituximab four times during that year. Everolimus: The initial dose of everolimus will be 2.5mg orally daily for a total of one year to maintain a target trough concentration between 3-15 ng/mL. Previously the study allowed for starting doses of 5mg and 10mg; the starting dose was reduced in subsequent amendments due to a high incidence of dose reductions. 2.5mg was the most frequent daily dose for all patients, and the entire population was analyzed as one arm. Rituximab: 375mg/m2 day +1 and then every 90 days for 1 year (a total of 4 infusions)
Overall Study Adverse Event	3
Overall Study Lack of Efficacy	19
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Maintenance Rituximab With mTor Inhibition After High-dose Consolidative Therapy in Lymphoma

Baseline characteristics by cohort

Measure	Everolimus and Rituximab n=49 Participants Everolimus daily for one year and IV rituximab four times during that year. Everolimus: The initial dose of everolimus will be 2.5mg orally daily for a total of one year to maintain a target trough concentration between 3-15 ng/mL. Previously the study allowed for starting doses of 5mg and 10mg; the starting dose was reduced in subsequent amendments due to a high incidence of dose reductions. 2.5mg was the most frequent daily dose for all patients, and the entire population was analyzed as one arm. Rituximab: 375mg/m2 day +1 and then every 90 days for 1 year (a total of 4 infusions)
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	37 Participants n=5 Participants
Age, Categorical >=65 years	12 Participants n=5 Participants
Age, Continuous	59 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	46 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 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	3 Participants n=5 Participants
Race (NIH/OMB) White	43 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Number of Prior Therapies Two Prior Therapies	30 Participants n=5 Participants
Number of Prior Therapies Three Prior Therapies	18 Participants n=5 Participants
Number of Prior Therapies Four Prior Therapies	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 3 years

Number of participants who did not experience at least one grade 3-4 adverse event by CTCAE 4.0.

Outcome measures

Measure

Everolimus and Rituximab n=49 Participants Everolimus daily for one year and IV rituximab four times during that year. Everolimus: The initial dose of everolimus will be 2.5mg orally daily for a total of one year to maintain a target trough concentration between 3-15 ng/mL. Previously the study allowed for starting doses of 5mg and 10mg; the starting dose was reduced in subsequent amendments due to a high incidence of dose reductions. 2.5mg was the most frequent daily dose for all patients, and the entire population was analyzed as one arm. Rituximab: 375mg/m2 day +1 and then every 90 days for 1 year (a total of 4 infusions)

Safety as Assessed by Avoidance of Grade 3-4 Adverse Events

1 Participants

SECONDARY outcome

Timeframe: 2.5 years

Percentage of participants alive without disease progression. As defined by Cheson criteria, disease progression is a new lesion or >= 50% increase in the size of previously identified sites of disease. EFS was estimated using Kaplan-Meier survival analysis.

Outcome measures

Measure

Everolimus and Rituximab n=49 Participants Everolimus daily for one year and IV rituximab four times during that year. Everolimus: The initial dose of everolimus will be 2.5mg orally daily for a total of one year to maintain a target trough concentration between 3-15 ng/mL. Previously the study allowed for starting doses of 5mg and 10mg; the starting dose was reduced in subsequent amendments due to a high incidence of dose reductions. 2.5mg was the most frequent daily dose for all patients, and the entire population was analyzed as one arm. Rituximab: 375mg/m2 day +1 and then every 90 days for 1 year (a total of 4 infusions)

Event Free Survival (EFS)

58 percentage of participants Interval 45.0 to 76.0

SECONDARY outcome

Timeframe: Baseline, 1 year, 2 years and 3 years

Population: Data was not collected.

Percentage change in circulating cancer cells between baseline and each timepoint noted below.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year, 2 years, and 3 years

Population: Data was not collected.

Percentage change in cancer cells when mTOR inhibition is applied in the laboratory. Samples from participants will be evaluated at each timepoint noted below.

Outcome measures

Outcome data not reported

Adverse Events

Everolimus and Rituximab

Serious events: 13 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Measure	Everolimus and Rituximab n=49 participants at risk Everolimus daily for one year and IV rituximab four times during that year. Everolimus: The initial dose of everolimus will be 2.5mg orally daily for a total of one year to maintain a target trough concentration between 3-15 ng/mL. Previously the study allowed for starting doses of 5mg and 10mg; the starting dose was reduced in subsequent amendments due to a high incidence of dose reductions. 2.5mg was the most frequent daily dose for all patients, and the entire population was analyzed as one arm. Rituximab: 375mg/m2 day +1 and then every 90 days for 1 year (a total of 4 infusions)
Renal and urinary disorders Acute kidney injury	4.1% 2/49 • Number of events 2 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	2.0% 1/49 • Number of events 1 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Infections and infestations Cellulitis	8.2% 4/49 • Number of events 4 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Gastrointestinal disorders Diarrhea	2.0% 1/49 • Number of events 1 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Investigations Hyperglycemia	2.0% 1/49 • Number of events 1 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Infections and infestations MRSA	2.0% 1/49 • Number of events 1 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Infections and infestations Febrile neutropenia	4.1% 2/49 • Number of events 2 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Infections and infestations Pneumonia	4.1% 2/49 • Number of events 2 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Infections and infestations Sepsis	6.1% 3/49 • Number of events 3 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.0% 1/49 • Number of events 1 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Eye disorders Retinal tear	2.0% 1/49 • Number of events 1 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Infections and infestations Zoster	2.0% 1/49 • Number of events 1 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Skin and subcutaneous tissue disorders Skin lesions	2.0% 1/49 • Number of events 1 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.

Other adverse events

Measure	Everolimus and Rituximab n=49 participants at risk Everolimus daily for one year and IV rituximab four times during that year. Everolimus: The initial dose of everolimus will be 2.5mg orally daily for a total of one year to maintain a target trough concentration between 3-15 ng/mL. Previously the study allowed for starting doses of 5mg and 10mg; the starting dose was reduced in subsequent amendments due to a high incidence of dose reductions. 2.5mg was the most frequent daily dose for all patients, and the entire population was analyzed as one arm. Rituximab: 375mg/m2 day +1 and then every 90 days for 1 year (a total of 4 infusions)
Investigations ALT increased	8.2% 4/49 • Number of events 6 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Investigations Anemia	10.2% 5/49 • Number of events 12 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Gastrointestinal disorders Diarrhea	6.1% 3/49 • Number of events 3 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.1% 3/49 • Number of events 3 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
General disorders Fatigue	6.1% 3/49 • Number of events 3 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Investigations Hyperglycemia	20.4% 10/49 • Number of events 25 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Investigations Hypertriglyceridemia	20.4% 10/49 • Number of events 17 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
General disorders Insomnia	6.1% 3/49 • Number of events 3 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Investigations Leukopenia	63.3% 31/49 • Number of events 73 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Investigations Lymphopenia	12.2% 6/49 • Number of events 15 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Skin and subcutaneous tissue disorders Mucositis	8.2% 4/49 • Number of events 4 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Nervous system disorders Neuropathy	8.2% 4/49 • Number of events 5 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Investigations Neutropenia	59.2% 29/49 • Number of events 75 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
General disorders Pain - throat	6.1% 3/49 • Number of events 4 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Skin and subcutaneous tissue disorders Rash	6.1% 3/49 • Number of events 3 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.
Investigations Thrombocytopenia	16.3% 8/49 • Number of events 18 • Up to 3 years Adverse events were assessed every 2 weeks for the first 2 months, monthly for the remainder of the first year, every 90 days for the second year, and every 6 months for the third year. Per protocol, all adverse events were collected for the first 13 participants. Only grade 3-4 and all serious adverse events were collected for the remaining participants.

Additional Information

Douglas Gladstone, MD

Johns Hopkins University

Phone: 4109558781

Email: dgladst1@jhmi.edu

Results disclosure agreements

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