Trial Outcomes & Findings for Study of High-Dose Rituximab With Temozolomide as Treatment for Primary Central Nervous System (CNS) Lymphoma (NCT NCT02113007)

Results Overview

Patients will be assessed for response by MRI of brain and/or spine after 4 cycles (8 weeks) of treatment according to Response Criteria for Primary CNS Lymphoma. Patients with stable disease or better (CR or PR) will continue treatment for 12 cycles (24 weeks). Complete Response (CR)=no contrast enhancement, normal eye exam. Partial Response (PR)=50 percent decrease in tumor enhancement, minor retinal pigment epithelium abnormality in eye exam. Stable disease (SD)= a change in lesion size that is neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for progressive disease.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

2 participants

Primary outcome timeframe

approximately 32 weeks

Results posted on

2017-02-07

Participant Flow

In August 2015, 2 patients with confirmed primary central nervous system (CNS) lymphoma were enrolled in the trial. Only one (of 4) investigational sites in the U.S accrued patients. Due to slow enrollment, the study was terminated in February 2016.

Participant milestones

Participant milestones
Measure	Rituximab Plus Temozolomide Rituximab: 375 mg/m2 IV, days 1, 3, and 5 Temozolomide: 150 mg/m2 PO, days 1-5 Rituximab plus Temozolomide: Treatment cycles will be repeated every 14 days (2 weeks) for the lead-in portion. If no prohibitive toxicities are observed in the first 6 patients during the first 2 treatment cycles, the study will continue enrolling patients. Treatment cycles for the Phase II portion will be repeated every 14 days (2 weeks) for a total of 12 cycles.
Overall Study STARTED	2
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Rituximab Plus Temozolomide Rituximab: 375 mg/m2 IV, days 1, 3, and 5 Temozolomide: 150 mg/m2 PO, days 1-5 Rituximab plus Temozolomide: Treatment cycles will be repeated every 14 days (2 weeks) for the lead-in portion. If no prohibitive toxicities are observed in the first 6 patients during the first 2 treatment cycles, the study will continue enrolling patients. Treatment cycles for the Phase II portion will be repeated every 14 days (2 weeks) for a total of 12 cycles.
Overall Study Progressive disease	2

Baseline Characteristics

Study of High-Dose Rituximab With Temozolomide as Treatment for Primary Central Nervous System (CNS) Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab Plus Temozolomide n=2 Participants Rituximab: 375 mg/m2 IV, days 1, 3, and 5 Temozolomide: 150 mg/m2 PO, days 1-5 Rituximab plus Temozolomide: Treatment cycles will be repeated every 14 days (2 weeks) for the lead-in portion. If no prohibitive toxicities are observed in the first 6 patients during the first 2 treatment cycles, the study will continue enrolling patients. Treatment cycles for the Phase II portion will be repeated every 14 days (2 weeks) for a total of 12 cycles.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Gender Female	1 Participants n=5 Participants
Gender Male	1 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	2 participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants

PRIMARY outcome

Timeframe: approximately 32 weeks

Population: The study closed early due to slow accrual. This outcome measure was not reached.

Patients will be assessed for response by MRI of brain and/or spine after 4 cycles (8 weeks) of treatment according to Response Criteria for Primary CNS Lymphoma. Patients with stable disease or better (CR or PR) will continue treatment for 12 cycles (24 weeks). Complete Response (CR)=no contrast enhancement, normal eye exam. Partial Response (PR)=50 percent decrease in tumor enhancement, minor retinal pigment epithelium abnormality in eye exam. Stable disease (SD)= a change in lesion size that is neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for progressive disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 and 12 months

Population: The study closed early due to slow accrual; outcome measure not reached.

Six and twelve-month CNS progression-free survival rate.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 4 weeks

Patients in the safety lead-in part of the study were monitored for up to 2 treatment cycles (4 weeks) to assure there were no unexpected or prohibitive toxicities. A non-serious adverse event is any untoward medical occurrence. A serious adverse event (SAE) is an event that meets one or more of the following: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; requires intervention to prevent permanent impairment or damage. Specific AE and SAE terms are provided in the Adverse event module.

Outcome measures

Outcome measures
Measure	Rituximab Plus Temozolomide n=2 Participants Rituximab: 375 mg/m2 IV, days 1, 3, and 5 Temozolomide: 150 mg/m2 PO, days 1-5 Rituximab plus Temozolomide: Treatment cycles will be repeated every 14 days (2 weeks) for the lead-in portion. If no prohibitive toxicities are observed in the first 6 patients during the first 2 treatment cycles, the study will continue enrolling patients. Treatment cycles for the Phase II portion will be repeated every 14 days (2 weeks) for a total of 12 cycles.
Number of Participants With Serious and Non-serious Adverse Events as a Measure of Safety. Adverse Events	2 participants
Number of Participants With Serious and Non-serious Adverse Events as a Measure of Safety. Serious Adverse Events	1 participants

Adverse Events

Rituximab Plus Temozolomide

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rituximab Plus Temozolomide n=2 participants at risk Rituximab: 375 mg/m2 IV, days 1, 3, and 5 Temozolomide: 150 mg/m2 PO, days 1-5 Rituximab plus Temozolomide: Treatment cycles will be repeated every 14 days (2 weeks) for the lead-in portion. If no prohibitive toxicities are observed in the first 6 patients during the first 2 treatment cycles, the study will continue enrolling patients. Treatment cycles for the Phase II portion will be repeated every 14 days (2 weeks) for a total of 12 cycles.
Metabolism and nutrition disorders Hyponatraemia	50.0% 1/2 • Number of events 1 • Adverse events and serious adverse events were collected for up to 4 weeks during the safety lead-in part of the study. The study closed early due to slow accrual.
Metabolism and nutrition disorders Hypoglycemia	50.0% 1/2 • Number of events 1 • Adverse events and serious adverse events were collected for up to 4 weeks during the safety lead-in part of the study. The study closed early due to slow accrual.

Other adverse events

Other adverse events
Measure	Rituximab Plus Temozolomide n=2 participants at risk Rituximab: 375 mg/m2 IV, days 1, 3, and 5 Temozolomide: 150 mg/m2 PO, days 1-5 Rituximab plus Temozolomide: Treatment cycles will be repeated every 14 days (2 weeks) for the lead-in portion. If no prohibitive toxicities are observed in the first 6 patients during the first 2 treatment cycles, the study will continue enrolling patients. Treatment cycles for the Phase II portion will be repeated every 14 days (2 weeks) for a total of 12 cycles.
Gastrointestinal disorders Flatulence	50.0% 1/2 • Adverse events and serious adverse events were collected for up to 4 weeks during the safety lead-in part of the study. The study closed early due to slow accrual.
Nervous system disorders Hypersomnia	50.0% 1/2 • Adverse events and serious adverse events were collected for up to 4 weeks during the safety lead-in part of the study. The study closed early due to slow accrual.
Metabolism and nutrition disorders Hypoalbuminemia	50.0% 1/2 • Adverse events and serious adverse events were collected for up to 4 weeks during the safety lead-in part of the study. The study closed early due to slow accrual.
General disorders Gait disturbance	50.0% 1/2 • Adverse events and serious adverse events were collected for up to 4 weeks during the safety lead-in part of the study. The study closed early due to slow accrual.
General disorders Fatigue	100.0% 2/2 • Adverse events and serious adverse events were collected for up to 4 weeks during the safety lead-in part of the study. The study closed early due to slow accrual.

Additional Information

Charles H. Davis, RAC

Sarah Cannon Development Innovations

Phone: 615-524-4341

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can review/embargo results communications prior to public release for a period that is \>60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.
Publication restrictions are in place

Restriction type: OTHER