Trial Outcomes & Findings for The Addition of Temozolomide to Conditioning for Autologous Transplantation in Relapsed & Refractory CNS Lymphoma (NCT NCT01235793)
NCT ID: NCT01235793
Last Updated: 2018-11-20
Results Overview
Efficacy of the DRBEAT Regimen will be assessed by analysis of 1. one-year progression-free survival (PFS), defined as the time interval from maximal response from therapy to tumor regrowth, progression\*, or death, (\*Progression is defined as meeting the response criteria listed in Table 4: Response Criteria for Primary Central Nervous System Lymphoma according to Abrey LE, Batchelor TT, Ferreri AJM et al.) and 2. Overall survival, defined as the time interval between the date of transplant and the date of death from any cause.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
11 participants
Primary outcome timeframe
(1) One Year (2) Until date of death from any cause, assessed up to 2 years
Results posted on
2018-11-20
Participant Flow
Participant milestones
| Measure |
DRBEAT Regimen
Temozolomide: The DRBEAT regimen will be similar to RBEAM. Rituximab and Carmustine will be given Day -6. Etoposide and Cytarabine will be given on Days -5 to -2. Temozolomide will be given via divided doses over five days starting on Day -5 to Day -1. A dose escalation design, known as EWOC (Escalation with overdose control) will be used to determine the target dose of temozolomide for this study. The starting dose given over five days will begin at 250mg/m\^2 (cumulative total dose of 1250 mg/m\^2), as previous data indicates this to be a safe dose. Based on the reported Dose Limiting toxicities from the previous patients, the EWOC statistical modeling will be performed to determine the next dose level.
|
|---|---|
|
Overall Study
STARTED
|
11
|
|
Overall Study
COMPLETED
|
5
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
| Measure |
DRBEAT Regimen
Temozolomide: The DRBEAT regimen will be similar to RBEAM. Rituximab and Carmustine will be given Day -6. Etoposide and Cytarabine will be given on Days -5 to -2. Temozolomide will be given via divided doses over five days starting on Day -5 to Day -1. A dose escalation design, known as EWOC (Escalation with overdose control) will be used to determine the target dose of temozolomide for this study. The starting dose given over five days will begin at 250mg/m\^2 (cumulative total dose of 1250 mg/m\^2), as previous data indicates this to be a safe dose. Based on the reported Dose Limiting toxicities from the previous patients, the EWOC statistical modeling will be performed to determine the next dose level.
|
|---|---|
|
Overall Study
Death
|
6
|
Baseline Characteristics
The Addition of Temozolomide to Conditioning for Autologous Transplantation in Relapsed & Refractory CNS Lymphoma
Baseline characteristics by cohort
| Measure |
DRBEAT Regimen
n=11 Participants
Temozolomide: The DRBEAT regimen will be similar to RBEAM. Rituximab and Carmustine will be given Day -6. Etoposide and Cytarabine will be given on Days -5 to -2. Temozolomide will be given via divided doses over five days starting on Day -5 to Day -1. A dose escalation design, known as EWOC (Escalation with overdose control) will be used to determine the target dose of temozolomide for this study. The starting dose given over five days will begin at 250mg/m\^2 (cumulative total dose of 1250 mg/m\^2), as previous data indicates this to be a safe dose. Based on the reported Dose Limiting toxicities from the previous patients, the EWOC statistical modeling will be performed to determine the next dose level.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
6 Participants
n=93 Participants
|
|
Age, Continuous
|
58 Age in years
n=93 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: (1) One Year (2) Until date of death from any cause, assessed up to 2 yearsEfficacy of the DRBEAT Regimen will be assessed by analysis of 1. one-year progression-free survival (PFS), defined as the time interval from maximal response from therapy to tumor regrowth, progression\*, or death, (\*Progression is defined as meeting the response criteria listed in Table 4: Response Criteria for Primary Central Nervous System Lymphoma according to Abrey LE, Batchelor TT, Ferreri AJM et al.) and 2. Overall survival, defined as the time interval between the date of transplant and the date of death from any cause.
Outcome measures
| Measure |
DRBEAT Regimen
n=11 Participants
Temozolomide: The DRBEAT regimen will be similar to RBEAM. Rituximab and Carmustine will be given Day -6. Etoposide and Cytarabine will be given on Days -5 to -2. Temozolomide will be given via divided doses over five days starting on Day -5 to Day -1. A dose escalation design, known as EWOC (Escalation with overdose control) will be used to determine the target dose of temozolomide for this study. The starting dose given over five days will begin at 250mg/m2 (cumulative total dose of 1250 mg/m2), as previous data indicates this to be a safe dose. Based on the reported Dose Limiting toxicities from the previous patients, the EWOC statistical modeling will be performed to determine the next dose level.
|
|---|---|
|
One-year Progression-free Survival and Overall Survival
Progression Free Survival
|
132 Days
Interval 38.0 to
95% confidence interval upper bound not obtained (insufficient number of participants with events)
|
|
One-year Progression-free Survival and Overall Survival
Overall Survival
|
564 Days
Interval 71.0 to
95% confidence interval upper bound not obtained (insufficient number of participants with events)
|
PRIMARY outcome
Timeframe: One YearSafety will be assessed using a dose escalation design for temozolomide's use to determine the target dose and also to evaluate any and all acute treatment related toxicities. During the course of patient follow up and therapy, toxicities will be evaluated, particularly as the investigators will be determining the target dose of temozolomide. One of the major criteria for dose limiting toxicity for the study will be any Grade 3 or 4 nonhematologic toxicity from a list of commonly expected toxicities associated with autologous transplantation and temozolomide.
Outcome measures
| Measure |
DRBEAT Regimen
n=11 Participants
Temozolomide: The DRBEAT regimen will be similar to RBEAM. Rituximab and Carmustine will be given Day -6. Etoposide and Cytarabine will be given on Days -5 to -2. Temozolomide will be given via divided doses over five days starting on Day -5 to Day -1. A dose escalation design, known as EWOC (Escalation with overdose control) will be used to determine the target dose of temozolomide for this study. The starting dose given over five days will begin at 250mg/m2 (cumulative total dose of 1250 mg/m2), as previous data indicates this to be a safe dose. Based on the reported Dose Limiting toxicities from the previous patients, the EWOC statistical modeling will be performed to determine the next dose level.
|
|---|---|
|
Safest Dose of Temozolomide for the DRBEAT Regimen
|
773.25 dose in mg/m^2
Interval 496.38 to 1000.0
|
Adverse Events
DRBEAT Regimen
Serious events: 6 serious events
Other events: 11 other events
Deaths: 6 deaths
Serious adverse events
| Measure |
DRBEAT Regimen
n=11 participants at risk
Temozolomide: The DRBEAT regimen will be similar to RBEAM. Rituximab and Carmustine will be given Day -6. Etoposide and Cytarabine will be given on Days -5 to -2. Temozolomide will be given via divided doses over five days starting on Day -5 to Day -1. A dose escalation design, known as EWOC (Escalation with overdose control) will be used to determine the target dose of temozolomide for this study. The starting dose given over five days will begin at 250mg/m\^2 (cumulative total dose of 1250 mg/m\^2), as previous data indicates this to be a safe dose. Based on the reported Dose Limiting toxicities from the previous patients, the EWOC statistical modeling will be performed to determine the next dose level.
|
|---|---|
|
Nervous system disorders
Encephalopathy
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Nervous system disorders
Gait disturbances
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Renal and urinary disorders
Renal and Urinary disorders -Other, specify: High squamous epithelial cells
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Infections and infestations
Sepsis
|
27.3%
3/11 • Number of events 3 • Over a two year period, from start of research therapy to 2 years post treatment.
|
Other adverse events
| Measure |
DRBEAT Regimen
n=11 participants at risk
Temozolomide: The DRBEAT regimen will be similar to RBEAM. Rituximab and Carmustine will be given Day -6. Etoposide and Cytarabine will be given on Days -5 to -2. Temozolomide will be given via divided doses over five days starting on Day -5 to Day -1. A dose escalation design, known as EWOC (Escalation with overdose control) will be used to determine the target dose of temozolomide for this study. The starting dose given over five days will begin at 250mg/m\^2 (cumulative total dose of 1250 mg/m\^2), as previous data indicates this to be a safe dose. Based on the reported Dose Limiting toxicities from the previous patients, the EWOC statistical modeling will be performed to determine the next dose level.
|
|---|---|
|
Investigations
Alanine aminotransferase increased
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Investigations
Alkaline phosphatase increased
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Immune system disorders
Allergic reaction
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Blood and lymphatic system disorders
Anemia
|
45.5%
5/11 • Number of events 5 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Investigations
Aspartate aminotransferase increased
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Blood and lymphatic system disorders
Blood and lymphatic disorders -Other, specify: Pancytopenia
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Investigations
Blood bilirubin increased
|
18.2%
2/11 • Number of events 2 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Musculoskeletal and connective tissue disorders
Facial muscle weakness
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
General disorders
Fatigue
|
18.2%
2/11 • Number of events 2 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
81.8%
9/11 • Number of events 11 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Metabolism and nutrition disorders
Hypertryglyceridemia
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
18.2%
2/11 • Number of events 2 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Vascular disorders
Hypotension
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Infections and infestations
Infections and infestations -Other, specify: Ecoli bacteria
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Blood and lymphatic system disorders
Leukocytosis
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Infections and infestations
Lung infection
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Investigations
Lymphocyte count decreased
|
27.3%
3/11 • Number of events 5 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Gastrointestinal disorders
Mucositis oral
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders -Other, specify: Neck weakness
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Investigations
Neutrophil count decreased
|
27.3%
3/11 • Number of events 5 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Investigations
Platelet count decreased
|
81.8%
9/11 • Number of events 10 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Nervous system disorders
Somnolence
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Renal and urinary disorders
Urinary incontinence
|
9.1%
1/11 • Number of events 1 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Renal and urinary disorders
Urinary tract infection
|
27.3%
3/11 • Number of events 5 • Over a two year period, from start of research therapy to 2 years post treatment.
|
|
Investigations
White blood cell decreased
|
45.5%
5/11 • Number of events 9 • Over a two year period, from start of research therapy to 2 years post treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place