Trial Outcomes & Findings for Combination Chemotherapy, Monoclonal Antibody, and Radiation Therapy in Treating Patients With Primary Central Nervous System Lymphoma (NCT NCT00068250)

Last Updated: 2018-02-07

Results Overview

A dose limiting toxicity (DLT) is defined as any grade 3 or 4 non-hematological toxicity (other than grade 3 nausea/vomiting) or any hematological toxicity resulting in the discontinuation of temozolomide. Toxicity evaluation for this dose escalation includes all toxicities occurring prior to the start of radiation therapy. If the patient did not receive radiation therapy, then toxicity evaluation included all toxicities occurring through week 15. Any grade 5 toxicity would result in immediate suspension of accrual.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

60 participants

Primary outcome timeframe

From start of treatment to 10 weeks if radiation therapy received, to 15 weeks if not.

Results posted on

2018-02-07

Participant Flow

Participant milestones

Participant milestones
Measure	Phase I: Temozolomide 100 mg Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.	Phase I: Temozolomide 150 mg Rituximab, methotrexate, temozolomide 150 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.	Phase II: Temozolomide 100 mg Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.
Phase I: Dose Level 1 STARTED	6	0	0
Phase I: Dose Level 1 COMPLETED	6	0	0
Phase I: Dose Level 1 NOT COMPLETED	0	0	0
Phase I: Dose Level 2 STARTED	0	7	0
Phase I: Dose Level 2 COMPLETED	0	6	0
Phase I: Dose Level 2 NOT COMPLETED	0	1	0
Phase II: Dose Level 2 STARTED	0	0	47
Phase II: Dose Level 2 COMPLETED	0	0	47
Phase II: Dose Level 2 NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I: Temozolomide 100 mg Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.	Phase I: Temozolomide 150 mg Rituximab, methotrexate, temozolomide 150 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.	Phase I: Temozolomide 200 mg Rituximab, methotrexate, temozolomide 200 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.	Phase II: Temozolomide 100 mg Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.
Phase I: Dose Level 2 Protocol Violation	0	1	0	0

Baseline Characteristics

Combination Chemotherapy, Monoclonal Antibody, and Radiation Therapy in Treating Patients With Primary Central Nervous System Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I: Temozolomide 100 mg n=6 Participants Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.	Phase I: Temozolomide 150 mg n=6 Participants Rituximab, methotrexate, temozolomide 150 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.	Phase II: Temozolomide 100 mg n=47 Participants Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.	Total n=59 Participants Total of all reporting groups
Age, Continuous	57 years n=5 Participants	62 years n=7 Participants	57 years n=5 Participants	57 years n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	2 Participants n=7 Participants	24 Participants n=5 Participants	30 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	4 Participants n=7 Participants	23 Participants n=5 Participants	29 Participants n=4 Participants

PRIMARY outcome

Timeframe: From start of treatment to 10 weeks if radiation therapy received, to 15 weeks if not.

Population: Eligible patients on Phase I arms who started study treatment

Outcome measures

Outcome measures
Measure	Phase I: Temozolomide 100mg n=6 Participants Phase I: Temozolomide 100mg	Phase I: Temozolomide150 mg n=6 Participants Phase I: Temozolomide 150 mg
Number of Phase I Participants Experiencing Toxicity	1 Participants	3 Participants

PRIMARY outcome

Timeframe: Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.

Population: Eligible patients on Temozolomide 100 mg arms who started study treatment

Survival time is defined as time from registration to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. (Please note that this outcome measure is considered the primary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions. )

Outcome measures

Outcome measures
Measure	Phase I: Temozolomide 100mg n=53 Participants Phase I: Temozolomide 100mg	Phase I: Temozolomide150 mg Phase I: Temozolomide 150 mg
Phase II: Overall Survival Rate at 2 Years (Including Phase I Patients at Same Dose)	80.8 percentage of participants Interval 70.1 to 91.5	—

SECONDARY outcome

Timeframe: From start of treatment to 10 weeks if RT received, to 15 weeks if not.

Population: Eligible patients on Temozolomide 100 mg arms who started study treatment and have scans for central review

Tumor response was centrally reviewed. Complete response: Disappearance of all enhancing tumor, the patient must be off steroid therapy and neurologically stable or improved; partial response: ≥ 50% decrease in enhancing tumor; progressive disease: ≥ 25% increase in a lesion, progressive or newly emergent meningeal or ocular disease. (Please note that this outcome measure is considered a secondary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions. )

Outcome measures

Outcome measures
Measure	Phase I: Temozolomide 100mg n=35 Participants Phase I: Temozolomide 100mg	Phase I: Temozolomide150 mg Phase I: Temozolomide 150 mg
Phase II: Pre-irradiation Chemotherapy Tumor Response Rate (Including Phase I Patients at Same Dose) Complete Response	18 Participants	—
Phase II: Pre-irradiation Chemotherapy Tumor Response Rate (Including Phase I Patients at Same Dose) Partial Response	12 Participants	—
Phase II: Pre-irradiation Chemotherapy Tumor Response Rate (Including Phase I Patients at Same Dose) Progressive Disease	2 Participants	—
Phase II: Pre-irradiation Chemotherapy Tumor Response Rate (Including Phase I Patients at Same Dose) Not evaluable	3 Participants	—

SECONDARY outcome

Timeframe: Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years.

Population: Eligible patients on Temozolomide 100 mg arms who started study treatment

Progression is defined as greater than 25% increase in enhancing tumor or the appearance of new lesions in the brain, eye, or the appearance of a new positive cerebrospinal fluid (CSF) cytology. The patient may be neurologically stable or worse and on stable or increasing doses of corticosteroid. Progression-free survival time is defined as time from registration to the date of progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. (Please note that this outcome measure is considered a secondary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions. )

Outcome measures

Outcome measures
Measure	Phase I: Temozolomide 100mg n=53 Participants Phase I: Temozolomide 100mg	Phase I: Temozolomide150 mg Phase I: Temozolomide 150 mg
Phase II: Progression-free Survival (Including Phase I Patients at Same Dose)	5.4 years Interval 1.8 to 7.3	—

Adverse Events

Phase I: Temozolomide 100 mg

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase I: Temozolomide 150 mg

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase II: Temozolomide 100 mg

Serious events: 16 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Wendy Seiferheld, M.S.

NRG Oncology

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	Phase I: Temozolomide 100 mg n=6 participants at risk Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.	Phase I: Temozolomide 150 mg n=6 participants at risk Rituximab, methotrexate, temozolomide 150 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.	Phase II: Temozolomide 100 mg n=47 participants at risk Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.1% 1/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Blood and lymphatic system disorders Hemoglobin decreased	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.1% 1/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Vomiting NOS	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.1% 1/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
General disorders Fatigue	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.1% 1/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
General disorders Late RT Toxicity:Other NOS	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.1% 1/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
General disorders Pain-other	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	16.7% 1/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Investigations Alanine aminotransferase increased	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	16.7% 1/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Investigations Aspartate aminotransferase increased	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	16.7% 1/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Investigations Leukopenia NOS	33.3% 2/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	16.7% 1/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	10.6% 5/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Investigations Neutropenia	50.0% 3/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	33.3% 2/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	10.6% 5/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Investigations Platelet count decreased	16.7% 1/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	16.7% 1/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	14.9% 7/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Metabolism and nutrition disorders Alkalosis NOS	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.1% 1/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Metabolism and nutrition disorders Hyperglycemia NOS	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	4.3% 2/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Nervous system disorders Ataxia NEC	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.1% 1/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Nervous system disorders Convulsions NOS	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	16.7% 1/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Nervous system disorders Encephalopathy NOS	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.1% 1/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Nervous system disorders Headache NOS	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.1% 1/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Nervous system disorders Learning disorder NOS	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.1% 1/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Nervous system disorders Peripheral motor neuropathy	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.1% 1/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Nervous system disorders Speech disorder NEC	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	4.3% 2/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Renal and urinary disorders Renal failure NOS	16.7% 1/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Vascular disorders Thrombosis NOS	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/6 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.1% 1/47 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.