Trial Outcomes & Findings for Study of Pralatrexate With Vitamin B12 and Folic Acid in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma (NCT NCT00364923)

NCT ID: NCT00364923

Last Updated: 2019-12-19

Results Overview

Patient response to treatment was determined by independent central review using International Workshop Criteria (IWC). Results present the best overall response. The initial response assessment was scheduled at week 7 (prior to Cycle 2) and then prior to every even-numbered cycle (every 14 weeks) for up to two years after first dose.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 115 participants
• Primary outcome timeframe: Response was assessed at 7 weeks (prior to Cycle 2) and then prior to every other even-numbered cycle (every 14 weeks) until disease progression or death for up to 2 years after initial dose
• Results posted on: 2019-12-19

Participant Flow

Patients were enrolled between 24 August 2006 and 14 April 2008 across 25 study sites, 15 sites in the United States (US), 8 in Europe, and 2 in Canada.

Patients (pts) were required to have at least 10 days of vitamin supplementation during the up to 12 days between enrollment & dosing. Four of the 115 pts enrolled were excluded during this period: 2 did not have an eligible PTCL subtype per central review, 1 had the presence of B-cell lymphoma per the investigator, 1 had progressive disease.

Participant milestones

Measure	Full Population All patients who received at least one dose of pralatrexate. Patients continued pralatrexate until protocol defined criteria for discontinuation or 24 months of treatment.
Treatment With Pralatrexate STARTED	111
Treatment With Pralatrexate COMPLETED	107
Treatment With Pralatrexate NOT COMPLETED	4
Survival Follow-up, After Pralatrexate STARTED	107
Survival Follow-up, After Pralatrexate COMPLETED	83
Survival Follow-up, After Pralatrexate NOT COMPLETED	24

Reasons for withdrawal

Measure	Full Population All patients who received at least one dose of pralatrexate. Patients continued pralatrexate until protocol defined criteria for discontinuation or 24 months of treatment.
Treatment With Pralatrexate Treatment with pralatrexate ongoing	4
Survival Follow-up, After Pralatrexate Pts still in follow-up at data cutoff	24

Baseline Characteristics

Study of Pralatrexate With Vitamin B12 and Folic Acid in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma

Baseline characteristics by cohort

Measure	Full Population n=111 Participants All patients who received at least one dose of pralatrexate
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	71 Participants n=5 Participants
Age, Categorical >=65 years	40 Participants n=5 Participants
Age, Continuous	57.7 years STANDARD_DEVIATION 15 • n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants
Sex: Female, Male Male	76 Participants n=5 Participants
Region of Enrollment United States	76 participants n=5 Participants
Region of Enrollment Canada	9 participants n=5 Participants
Region of Enrollment Europe	26 participants n=5 Participants

PRIMARY outcome

Timeframe: Response was assessed at 7 weeks (prior to Cycle 2) and then prior to every other even-numbered cycle (every 14 weeks) until disease progression or death for up to 2 years after initial dose

Population: Analysis was per protocol and was based on number of patients (pts) who responded in the evaluable population. The evaluable population consisted of all pts who received at least one dose of pralatrexate and had an eligible peripheral T-cell lymphoma (PTCL) histopathological subtype confirmed by central pathology review.

Patient response to treatment was determined by independent central review using International Workshop Criteria (IWC). Results present the best overall response. The initial response assessment was scheduled at week 7 (prior to Cycle 2) and then prior to every even-numbered cycle (every 14 weeks) for up to two years after first dose.

Outcome measures

Measure	Evaluable Population n=109 Participants All patients who received at least one dose of pralatrexate and had an eligible PTCL histopathological subtype confirmed by central pathology review.
Response Rate Per Independent Central Review	32 of Patients who Responded

SECONDARY outcome

Timeframe: Measured from the first day of documented response, assessed at prior to every other even-numbered cycle (every 14 weeks) until disease progression or death for up to 2 years after initial dose

Population: Analysis was per protocol. Based on the number of responding pts (n=32) in the evaluable population (n=109), as assessed by independent central review protocol.

Calculated only for those pts with an objective response. Pts receiving subsequent therapy (including transplant) before progressive disease (PD) was documented were censored at date of last response assessment obtained prior to subsequent therapy, with a note indicating censoring occurrence & reason. Pts who withdrew consent to participate in the study prior to PD were censored at the date of their last evaluable assessment of response. Pts who withdrew from treatment prior to PD or initiation of subsequent therapy without withdrawing consent were followed for disease status when possible.

Outcome measures

Measure	Evaluable Population n=32 Participants All patients who received at least one dose of pralatrexate and had an eligible PTCL histopathological subtype confirmed by central pathology review.
Duration of Response Per Independent Central Review	306 Days Interval 1.0 to 673.0

SECONDARY outcome

Timeframe: Calculated as the number of days from treatment day 1 to the date of disease progression or death, regardless of cause for up to 2 years after initial dose

Population: Analysis was per protocol, based on the number of patients (pts) who had an event of progressive disease (PD) or death. Pts who did not have an event at the time of data cut-off were censored. Pts were censored for lack of PD, receipt of other anti-cancer therapy before PD, termination of study/follow-up for response, and transplant.

Patients (pts) with subsequent therapy prior to PD were censored at date of last response assessment prior to subsequent therapy. Pts who were alive without PD were censored at the date of last assessment of first dose. Pts who withdrew consent to participate in the study prior to PD were censored at the date of their last disease assessment or treatment day 1. Pts who withdrew consent from treatment prior to PD without withdrawing consent for follow-up were followed for disease status & survival. Pts who did not have response assessments after baseline were censored at treatment day 1.

Outcome measures

Measure	Evaluable Population n=109 Participants All patients who received at least one dose of pralatrexate and had an eligible PTCL histopathological subtype confirmed by central pathology review.
Progression-free Survival Per Independent Central Review	106 Days Interval 1.0 to 726.0

SECONDARY outcome

Timeframe: Assessed every 14 weeks while on treatment, and after disease progression no less frequently than every 6 months for up to 2 years after first dose.

Population: Analysis was per protocol, based on the number of patients (pts) who had an event (death or censoring) at the time of data cut-off.

Calculated as date of death - date of enrollment +1, estimated using the product-limit estimator. Pts who had not died (no record of death) or were lost to follow-up were censored at the date of last contact. Pts who withdrew consent to participate in the study including consent to be followed, were censored on the date of withdrawal. Pts who withdrew from treatment without withdrawing consent were followed for survival status whenever possible.

Outcome measures

Measure	Evaluable Population n=109 Participants All patients who received at least one dose of pralatrexate and had an eligible PTCL histopathological subtype confirmed by central pathology review.
Overall Survival Per Independent Central Review	14.5 Months Interval 1.0 to 24.1

Adverse Events

Full Population

Serious events: 50 serious events

Other events: 111 other events

Deaths: 0 deaths

Serious adverse events

Measure	Full Population n=111 participants at risk All patients who received at least one dose of pralatrexate
Infections and infestations sepsis	4.5% 5/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Infections and infestations herpes zoster	2.7% 3/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Infections and infestations pneumonia	2.7% 3/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Infections and infestations urinary tract infection	1.8% 2/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Infections and infestations candidiasis	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Infections and infestations catheter site infection	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Infections and infestations cytomegalovirus colitis	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Infections and infestations infection	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Infections and infestations septic shock	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Infections and infestations sinusitis	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Infections and infestations upper respiratory tract infection	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Infections and infestations wound infection	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Blood and lymphatic system disorders febrile neutropenia	4.5% 5/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Blood and lymphatic system disorders neutropenia	2.7% 3/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Blood and lymphatic system disorders thrombocytopenia	2.7% 3/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Blood and lymphatic system disorders lymph node pain	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Blood and lymphatic system disorders pancytopenia	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
General disorders pyrexia	7.2% 8/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
General disorders fatigue	1.8% 2/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
General disorders mucosal inflammation	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
General disorders pain	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Gastrointestinal disorders stomatitis	4.5% 5/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Gastrointestinal disorders abdominal pain	1.8% 2/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Gastrointestinal disorders nausea	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Gastrointestinal disorders obstruction gastric	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Gastrointestinal disorders esophagitis	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Gastrointestinal disorders perianal erythema	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Gastrointestinal disorders polyp colorectal	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Gastrointestinal disorders vomiting	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Respiratory, thoracic and mediastinal disorders dyspnea	3.6% 4/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Respiratory, thoracic and mediastinal disorders epistaxis	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Respiratory, thoracic and mediastinal disorders pneumonitis	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Respiratory, thoracic and mediastinal disorders pulmonary embolism	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Metabolism and nutrition disorders dehydration	3.6% 4/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Metabolism and nutrition disorders hypercalcemia	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Metabolism and nutrition disorders hypomagnesemia	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Nervous system disorders cerebral infarction	1.8% 2/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Nervous system disorders carotid sinus syndrome	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Nervous system disorders convulsion	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Nervous system disorders ischemic stroke	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Vascular disorders hypotension	1.8% 2/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Vascular disorders subclavian vein thrombosis	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Vascular disorders superior vena caval occlusion	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Cardiac disorders atrial fibrillation	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Cardiac disorders cardiorespiratory arrest	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Cardiac disorders pericardial effusion	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Cardiac disorders ventricular tachycardia	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) bile duct cancer	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) tumor associated fever	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) tumor lysis syndrome	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Renal and urinary disorders renal failure actue	1.8% 2/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Skin and subcutaneous tissue disorders skin ulcer	1.8% 2/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Endocrine disorders inappropriate antidiuretic hormone secretion	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Hepatobiliary disorders cholecystitis acute	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Injury, poisoning and procedural complications excoriation	0.90% 1/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.

Other adverse events

Measure	Full Population n=111 participants at risk All patients who received at least one dose of pralatrexate
Gastrointestinal disorders stomatitis	68.5% 76/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Gastrointestinal disorders nausea	40.5% 45/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Gastrointestinal disorders constipation	34.2% 38/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Gastrointestinal disorders vomiting	25.2% 28/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Gastrointestinal disorders diarrhea	22.5% 25/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Gastrointestinal disorders abdominal pain	10.8% 12/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Gastrointestinal disorders abdominal pain upper	8.1% 9/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Gastrointestinal disorders gastroesophageal reflux disease	6.3% 7/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Gastrointestinal disorders flatulence	5.4% 6/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Gastrointestinal disorders hemorrhoids	5.4% 6/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Gastrointestinal disorders oral pain	5.4% 6/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
General disorders fatigue	34.2% 38/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
General disorders pyrexia	28.8% 32/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
General disorders edema peripheral	27.9% 31/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
General disorders asthenia	10.8% 12/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
General disorders mucosal inflammation	9.0% 10/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
General disorders pain	5.4% 6/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Respiratory, thoracic and mediastinal disorders cough	28.8% 32/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Respiratory, thoracic and mediastinal disorders epistaxis	26.1% 29/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Respiratory, thoracic and mediastinal disorders dyspnea	16.2% 18/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Respiratory, thoracic and mediastinal disorders pharyngolaryngeal pain	13.5% 15/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Skin and subcutaneous tissue disorders rash	15.3% 17/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Skin and subcutaneous tissue disorders pruritis	14.4% 16/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Skin and subcutaneous tissue disorders night sweats	10.8% 12/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Skin and subcutaneous tissue disorders skin lesion	7.2% 8/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Skin and subcutaneous tissue disorders skin ulcer	7.2% 8/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Skin and subcutaneous tissue disorders blister	5.4% 6/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Blood and lymphatic system disorders thrombocytopenia	29.7% 33/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Blood and lymphatic system disorders anemia	28.8% 32/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Blood and lymphatic system disorders neutropenia	19.8% 22/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Infections and infestations sinusitis	9.9% 11/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Infections and infestations upper respiratory tract infection	9.9% 11/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Infections and infestations nasopharyngitis	8.1% 9/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Infections and infestations folliculitis	5.4% 6/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Infections and infestations oral herpes	5.4% 6/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Musculoskeletal and connective tissue disorders back pain	12.6% 14/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Musculoskeletal and connective tissue disorders pain in extremity	11.7% 13/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Musculoskeletal and connective tissue disorders musculoskeletal pain	9.0% 10/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Musculoskeletal and connective tissue disorders arthralgia	7.2% 8/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Musculoskeletal and connective tissue disorders muscle spasms	7.2% 8/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Musculoskeletal and connective tissue disorders myalgia	6.3% 7/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Investigations platelet count decreased	11.7% 13/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Investigations alanine aminotransferase increased	9.0% 10/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Investigations hemoglobin decreased	8.1% 9/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Investigations weight decreased	7.2% 8/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Investigations white blood cell count decreased	6.3% 7/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Investigations neutrophil count decreased	5.4% 6/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Metabolism and nutrition disorders hypokalemia	15.3% 17/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Metabolism and nutrition disorders hypomagnesemia	9.0% 10/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Metabolism and nutrition disorders anorexia	8.1% 9/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Metabolism and nutrition disorders decreased appetite	8.1% 9/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Metabolism and nutrition disorders dehydration	5.4% 6/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Nervous system disorders headache	11.7% 13/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Nervous system disorders dizziness	9.0% 10/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Nervous system disorders paresthesia	5.4% 6/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Eye disorders eye irritation	6.3% 7/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Psychiatric disorders anxiety	7.2% 8/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Psychiatric disorders insomnia	5.4% 6/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.
Cardiac disorders tachycardia	9.9% 11/111 • All adverse events (AEs) were captured from the first dose of pralatrexate through 30 days after the last study treatment. From 31 days after the last dose of pralatrexate, pralatrexate-related AEs were recorded until the start of subsequent therapy. Serious AEs and AEs regardless of causality and all grades presented below. Symptoms present at baseline, AEs, and intercurrent illnesses were monitored at every study visit. Patients were instructed to report AEs to the investigator. All AEs including observed or volunteered problems, complaints, or symptoms were recorded.

Additional Information

Michael Saunders, M.D.

Allos Therapeutics, Inc

Phone: 303-426-6262

Email: msaunders@allos.com

Results disclosure agreements

• Principal investigator is a sponsor employee Allos agreements with investigators (PIs) may vary. The PI may publish/make public data from the trial after the earlier of publication by Allos or 18 months after study completion. Allos can review results communications prior to public release and can embargo communications regarding trial results for a period less than or equal to 90 days from submission for review. Allos can request changes to the communication related to confidential or patent information, or to ensure accuracy.
• Publication restrictions are in place

Restriction type: OTHER