Trial Outcomes & Findings for Pralatrexate vs Observation Following CHOP-based Chemotherapy in Undiagnosed Peripheral T-cell Lymphoma Patients (NCT NCT01420679)

NCT ID: NCT01420679

Last Updated: 2021-11-19

Results Overview

PFS was defined as the time in days from randomization to the date of objective documentation of progressive disease (PD) or death, regardless of cause (date of PD or death - date of randomization + 1). PFS was to be assessed according to the International Workshop Criteria (IWC) without including positron emission tomography (PET). PD was defined as any new lesion or increase by greater than or equal to (\>=) 50 percent (%) of previously involved sites from nadir. Participants who were alive without a disease response assessment of PD was to be censored at their last disease assessment date or the date of randomization, whichever was later. Date of progression was not to be imputed for participants with missing tumor assessments before an assessment of PD. Participants who withdraw from treatment prior to PD were to be followed for disease status whenever possible. Participants who have no response assessments after baseline were to be censored at randomization.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

21 participants

Primary outcome timeframe

From randomization to the date of progression of disease or death due to any cause (up to 76 months)

Results posted on

2021-11-19

Participant Flow

A total of 21 participants with peripheral T-cell lymphoma (PTCL) were randomized in 2:1 ratio to Pralatrexate arm or Observation arm.

Participant milestones

Participant milestones
Measure	Pralatrexate Arm Participants randomized to Pralatrexate Arm received pralatrexate as an intravenous (IV) push administered over a minimum of 30 seconds up to a maximum of 5 minutes via a patent free-flowing IV line containing normal saline (0.9% sodium chloride \[NaCl\]) weekly for 3 weeks of a 4-week cycle. Initial dose of pralatrexate was 30 milligram per meter square (mg/m\^2), could be reduced to 20 mg/m\^2 with potential further reductions to 15 and 10 mg/m\^2 based on toxicity, along with vitamin B12, 1 milligram (mg) intramuscular (IM), every 8-10 weeks and folic acid 1-1.25 mg by mouth (po) once a day (qd) until a criterion for study treatment discontinuation was met or up to a maximum of 2 years.	Observation Arm Participants randomized to Observation Arm received vitamin B12, 1 mg, IM every 8-10 weeks and folic acid 1-1.25 mg by mouth qd remained under observation, by attending clinic visits every 4 weeks, and being contacted by a healthcare professional during week 2 of every 4-week period until a criterion for study treatment discontinuation was met.
Overall Study STARTED	14	7
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	14	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Pralatrexate Arm Participants randomized to Pralatrexate Arm received pralatrexate as an intravenous (IV) push administered over a minimum of 30 seconds up to a maximum of 5 minutes via a patent free-flowing IV line containing normal saline (0.9% sodium chloride \[NaCl\]) weekly for 3 weeks of a 4-week cycle. Initial dose of pralatrexate was 30 milligram per meter square (mg/m\^2), could be reduced to 20 mg/m\^2 with potential further reductions to 15 and 10 mg/m\^2 based on toxicity, along with vitamin B12, 1 milligram (mg) intramuscular (IM), every 8-10 weeks and folic acid 1-1.25 mg by mouth (po) once a day (qd) until a criterion for study treatment discontinuation was met or up to a maximum of 2 years.	Observation Arm Participants randomized to Observation Arm received vitamin B12, 1 mg, IM every 8-10 weeks and folic acid 1-1.25 mg by mouth qd remained under observation, by attending clinic visits every 4 weeks, and being contacted by a healthcare professional during week 2 of every 4-week period until a criterion for study treatment discontinuation was met.
Overall Study Disease Progression	3	2
Overall Study Adverse Event	4	0
Overall Study More Than 28 Days Between Doses of Drug	1	0
Overall Study Patient Decision	1	0
Overall Study Investigator Decision	1	2
Overall Study Sponsor Decision	3	3
Overall Study Other	1	0

Baseline Characteristics

Pralatrexate vs Observation Following CHOP-based Chemotherapy in Undiagnosed Peripheral T-cell Lymphoma Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pralatrexate Arm n=14 Participants Participants randomized to Pralatrexate Arm received pralatrexate as an intravenous (IV) push administered over a minimum of 30 seconds up to a maximum of 5 minutes via a patent free-flowing IV line containing normal saline (0.9% sodium chloride \[NaCl\]) weekly for 3 weeks of a 4-week cycle. Initial dose of pralatrexate was 30 milligram per meter square (mg/m\^2), could be reduced to 20 mg/m\^2 with potential further reductions to 15 and 10 mg/m\^2 based on toxicity, along with vitamin B12, 1 milligram (mg) intramuscular (IM), every 8-10 weeks and folic acid 1-1.25 mg by mouth (po) once a day (qd) until a criterion for study treatment discontinuation was met or up to a maximum of 2 years.	Observation Arm n=7 Participants Participants randomized to Observation Arm received vitamin B12, 1 mg, IM every 8-10 weeks and folic acid 1-1.25 mg by mouth qd remained under observation, by attending clinic visits every 4 weeks, and being contacted by a healthcare professional during week 2 of every 4-week period until a criterion for study treatment discontinuation was met.	Total n=21 Participants Total of all reporting groups
Age, Continuous	72.0 years n=5 Participants	61.0 years n=7 Participants	68.0 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	0 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Arabic	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized Missing	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization to the date of progression of disease or death due to any cause (up to 76 months)

Population: Data for this outcome measure was not collected and analyzed due to the early termination of the study.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: From randomization until death (up to 76 months)

Population: ITT population included all randomized participants classified according to the treatment arms into which they were randomized, regardless of the actual study treatment received (or not received).

Overall survival was defined as the time in days from randomization to the date of death, regardless of cause (date of death - date of randomization + 1).

Outcome measures

Outcome measures
Measure	Pralatrexate Arm n=14 Participants Participants randomized to Pralatrexate Arm received pralatrexate as an intravenous (IV) push administered over a minimum of 30 seconds up to a maximum of 5 minutes via a patent free-flowing IV line containing normal saline (0.9% sodium chloride \[NaCl\]) weekly for 3 weeks of a 4-week cycle. Initial dose of pralatrexate was 30 milligram per meter square (mg/m\^2), could be reduced to 20 mg/m\^2 with potential further reductions to 15 and 10 mg/m\^2 based on toxicity, along with vitamin B12, 1 milligram (mg) intramuscular (IM), every 8-10 weeks and folic acid 1-1.25 mg by mouth (po) once a day (qd) until a criterion for study treatment discontinuation was met or up to a maximum of 2 years.	Observation Arm n=7 Participants Participants randomized to Observation Arm received vitamin B12, 1 mg, IM every 8-10 weeks and folic acid 1-1.25 mg by mouth qd remained under observation, by attending clinic visits every 4 weeks, and being contacted by a healthcare professional during week 2 of every 4-week period until a criterion for study treatment discontinuation was met.
Overall Survival (OS)	NA months Median and 95% CI were not estimable due to low number of participants with events.	NA months Median and 95% CI were not estimable due to low number of participants with events.

SECONDARY outcome

Timeframe: Up to 2 years

Population: Data for this outcome measure was not collected and analyzed due to early termination of the study.

Objective response rate was defined as percentage of participants with an objective response of complete response (CR) or partial response (PR), relative to disease status at the time of study entry. The percentage was to be calculated by dividing number of participants within each category of response by the number of participants with measurable disease at baseline. Objective response was assessed according to the IWC without including PET. CR was defined as complete disappearance all detectable clinical evidence of disease and disease-related symptoms if present before therapy. PR was defined as regression of measurable disease and no new sites.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years)

Population: Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. AE included both serious and non- SAEs. An AE of "Hematology and Chemistry" was collected and graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03, where Grade 3 refers to severe or medically significant but not immediately life threatening and Grade 4 refers to life-threatening consequences.

Outcome measures

Outcome measures
Measure	Pralatrexate Arm n=14 Participants Participants randomized to Pralatrexate Arm received pralatrexate as an intravenous (IV) push administered over a minimum of 30 seconds up to a maximum of 5 minutes via a patent free-flowing IV line containing normal saline (0.9% sodium chloride \[NaCl\]) weekly for 3 weeks of a 4-week cycle. Initial dose of pralatrexate was 30 milligram per meter square (mg/m\^2), could be reduced to 20 mg/m\^2 with potential further reductions to 15 and 10 mg/m\^2 based on toxicity, along with vitamin B12, 1 milligram (mg) intramuscular (IM), every 8-10 weeks and folic acid 1-1.25 mg by mouth (po) once a day (qd) until a criterion for study treatment discontinuation was met or up to a maximum of 2 years.	Observation Arm n=7 Participants Participants randomized to Observation Arm received vitamin B12, 1 mg, IM every 8-10 weeks and folic acid 1-1.25 mg by mouth qd remained under observation, by attending clinic visits every 4 weeks, and being contacted by a healthcare professional during week 2 of every 4-week period until a criterion for study treatment discontinuation was met.
Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Serious Adverse Events (SAEs), and SAEs Leading to Discontinuation of Study Treatment, and Worst Grade Laboratory Abnormalities Chemistry:Higher Than Grade 3/4 Lab Abnormalities	1 Participants	0 Participants
Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Serious Adverse Events (SAEs), and SAEs Leading to Discontinuation of Study Treatment, and Worst Grade Laboratory Abnormalities Participants with Any Treatment Emergent AEs	14 Participants	6 Participants
Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Serious Adverse Events (SAEs), and SAEs Leading to Discontinuation of Study Treatment, and Worst Grade Laboratory Abnormalities Participants with Any Grade 3 - 4 AEs	8 Participants	2 Participants
Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Serious Adverse Events (SAEs), and SAEs Leading to Discontinuation of Study Treatment, and Worst Grade Laboratory Abnormalities Participants with Treatment Emergent AEs Resulting in Deaths	1 Participants	0 Participants
Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Serious Adverse Events (SAEs), and SAEs Leading to Discontinuation of Study Treatment, and Worst Grade Laboratory Abnormalities Participants with Treatment Emergent SAEs	4 Participants	0 Participants
Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Serious Adverse Events (SAEs), and SAEs Leading to Discontinuation of Study Treatment, and Worst Grade Laboratory Abnormalities Participants with Any SAEs Leading to Drug Discontinuation	2 Participants	0 Participants
Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Serious Adverse Events (SAEs), and SAEs Leading to Discontinuation of Study Treatment, and Worst Grade Laboratory Abnormalities Hematology:Higher Than Grade 3/4 Lab Abnormalities	3 Participants	1 Participants

Adverse Events

Pralatrexate Arm

Serious events: 4 serious events

Other events: 14 other events

Deaths: 3 deaths

Observation Arm

Serious events: 0 serious events

Other events: 6 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Pralatrexate Arm n=14 participants at risk Participants randomized to Pralatrexate Arm received pralatrexate as an intravenous (IV) push administered over a minimum of 30 seconds up to a maximum of 5 minutes via a patent free-flowing IV line containing normal saline (0.9% sodium chloride \[NaCl\]) weekly for 3 weeks of a 4-week cycle. Initial dose of pralatrexate was 30 milligram per meter square (mg/m\^2), could be reduced to 20 mg/m\^2 with potential further reductions to 15 and 10 mg/m\^2 based on toxicity, along with vitamin B12, 1 milligram (mg) intramuscular (IM), every 8-10 weeks and folic acid 1-1.25 mg by mouth (po) once a day (qd) until a criterion for study treatment discontinuation was met or up to a maximum of 2 years.	Observation Arm n=7 participants at risk Participants randomized to Observation Arm received vitamin B12, 1 mg, IM every 8-10 weeks and folic acid 1-1.25 mg by mouth qd remained under observation, by attending clinic visits every 4 weeks, and being contacted by a healthcare professional during week 2 of every 4-week period until a criterion for study treatment discontinuation was met.
Cardiac disorders Cardiac arrest	7.1% 1/14 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/7 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Gastrointestinal disorders Stomatitis	7.1% 1/14 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/7 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
General disorders Non-cardiac chest pain	7.1% 1/14 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/7 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Injury, poisoning and procedural complications Subdural hematoma	7.1% 1/14 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/7 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Metabolism and nutrition disorders Hyponatraemia	7.1% 1/14 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/7 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Nervous system disorders Haemorrhage intracranial	7.1% 1/14 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/7 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Nervous system disorders Carotid artery occlusion	7.1% 1/14 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/7 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Nervous system disorders VIIth nerve paralysis	7.1% 1/14 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/7 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Psychiatric disorders Confusional state	7.1% 1/14 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/7 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.1% 1/14 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.	0.00% 0/7 • From first dose of study drug to 35 (±5) days after last dose of study drug for the Pralatrexate Arm, and until 35 (± 5) days after the study treatment discontinuation for the Observation Arm (Up to 2 years) Safety population included all randomized participants classified according to the actual study treatment received, regardless of random assignment.

Other adverse events

Additional Information

Gajanan Bhat

Spectrum Pharmaceuticals, Inc

Phone: 949-743-9219

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place