Study of Pralatrexate & Gemcitabine With B12 & Folic Acid... | NCT00481871

Label	Type	Description	Intervention Names
Pralatrexate & Gemcitabine - Sequential Days	Experimental		Drug: Pralatrexate Injection Drug: Gemcitabine Hydrochloride Dietary Supplement: Vitamin B12 Dietary Supplement: Folic Acid
Pralatrexate & Gemcitabine - Same Day	Experimental		Drug: Pralatrexate Injection Drug: Gemcitabine Hydrochloride Dietary Supplement: Vitamin B12 Dietary Supplement: Folic Acid

Name	Type	Description	Arm Group Labels	Other Names
Pralatrexate Injection	Drug	Intravenous (IV) push administration over 30 seconds to 5 minutes into a patent IV line containing normal saline (0.9% sodium chloride). Sequential Dosing: 10 mg/m2 every 2 weeks (days 1 and 15) of a 4-week cycle until criteria for discontinuation per the protocol are met. Same Day Dosing: 15 mg/m2 every 2 weeks (days 1 and 15) of a 4-week cycle until criteria for discontinuation per the protocol are met.

Measure	Description	Time Frame
Objective Responses Assessed by International Workshop Criteria (IWC)	Number of participants who achieved an objective response. Objective response was defined as a tumor response assessment of either complete response (CR) or partial response (PR) and was determined only for patients with measurable disease at baseline. A tumor response assessment reported by IWC without PET was used for any analyses in cases where an IWC+PET evaluation was not done.	Assessed every 8 weeks (+/- 1 week) for Phase II and no less than every 3 cycles for Phase I

Measure	Description	Time Frame
Duration of Response	Duration of response was defined as the number of days between the date of first tumor response assessment of objective response to the time of the first tumor response assessment of progressive disease (PD) or death due to any cause (date of first PD assessment or death - date of first objective response assessment + 1)	Response assessments were performed no less than every 3 cycles in the Phase 1 part of the study and every 8 weeks (± 1 week) in the Phase 2a part of the study

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Phase 1: Histologically/cytologically confirmed lymphoproliferative malignancy. Patients with Hodgkin lymphoma (HL) or non-HL are eligible, with exceptions per exclusion criteria.
Phase 2a: Histologically/cytologically confirmed HL, peripheral T-cell lymphoma (PTCL), or B-cell lymphoma including Waldenström's macroglobulinemia, with exceptions per exclusion criteria.
Progression of disease (PD) after at least 1 prior treatment (any number of prior therapies allowed). PD after last prior treatment and recovered from toxic effects of prior therapy. Patients treated with an FDA-approved monoclonal antibody therapy may be enrolled at any time after the therapy if they have PD.
PTCL patients must have received single-agent pralatrexate as a prior therapy.
Eastern Cooperative Oncology Group performance status ≤ 2.
Adequate blood, liver and kidney function per laboratory tests.
Has taken 1 mg daily oral folic acid for at least 7 days prior to planned start of pralatrexate and received 1 mg vitamin B12 intramuscularly within 10 weeks of the planned start of pralatrexate.
Females of childbearing potential must practice a medically acceptable contraceptive regimen from first dose until at least 30 days after last dose of pralatrexate and have a negative serum pregnancy test within 14 days prior to the first day of study treatment. Postmenopausal (defined as greater than 12 months since last menses) and surgically sterilized females do not require this test.
Males who are not surgically sterile must practice a medically acceptable contraceptive regimen from first dose until at least 90 days after last dose of pralatrexate.
Give written informed consent.

Exclusion Criteria:

Phase 1

1. B-cell: lymphoplasmacytic lymphoma (± Waldenström's macroglobulinemia); plasma cell myeloma/plasmacytoma; hairy cell leukemia.
Phase 2a
1. PTCL: precursor T/Natural Killer (NK) neoplasms, with the exception of blastic NK lymphoma; T-cell prolymphocytic leukemia; T-cell large granular lymphocytic leukemia; mycosis fungoides (MF), except transformed MF; Sézary syndrome; primary cutaneous CD30+ disorders: Anaplastic large cell lymphoma and lymphomatoid papulosis.
2. B-cell: plasma cell myeloma/plasmacytoma; hairy cell leukemia.
Relapsed HL or diffuse large B-cell lymphoma patients who are candidates for high dose therapy and autologous stem cell transplantation (SCT) and for whom it is a standard curative option.
Active concurrent malignancy (except non melanoma skin cancer or carcinoma in situ of the cervix). If there is a history of prior malignancy, must be disease free for at least 5 years.
Congestive heart failure Class III/IV.
Uncontrolled hypertension.
Human immunodeficiency virus (HIV)- positive diagnosis with CD4 less than 100 or detectable viral load within past 3 months and receiving anti-retroviral therapy.
Hepatitis B or C virus with detectable viral load or immunological evidence of chronic active disease or receiving/requiring antiviral therapy.
Central nervous system disease.
Undergone an allogeneic SCT.
Patients with disease refractory to peripheral blood SCT, or who have relapsed less than 100 days since an autologous or peripheral blood SCT.
Active uncontrolled infection, underlying medical condition including unstable heart disease, or other serious illness impairing the ability to receive protocol treatment.
Major surgery within 2 weeks of planned start of treatment.
Receipt of any conventional chemotherapy or radiation therapy (encompassing greater than 10% of bone marrow) within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study treatment or planned use during the study.
Receipt of systemic corticosteroids within 7 days of study treatment, unless on a continuous dose of no more than 10 mg/day of prednisone for at least 1 month.
Use of investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the study.
Received a monoclonal antibody within 3 months without evidence of PD.
Previous exposure to pralatrexate and/or gemcitabine if discontinued due to treatment-related toxicity.

Name	Affiliation	Role
Michael Saunders, MD	Spectrum Pharmaceuticals, Inc	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of California at Los Angeles		Los Angeles	California	90095-7077	United States
Stanford University School of Medicine

ID	Title	Description
FG000	Phase 1 Group A - Dose Finding	Phase 1 Treatment Group A had pralatrexate and gemcitabine administered on sequential days every week for 3 weeks followed by 1 week of rest (a 4 week cycle). The starting dose was 15 mg/m2 of pralatrexate and 400 mg/m2 of gemcitabine.
FG001	Phase 1 Group B - Dose Finding

ID	Title	Description
BG000	Phase 1 - Group A	Phase 1 Treatment Group A had pralatrexate and gemcitabine administered on sequential days every week for 3 weeks followed by 1 week of rest (a 4 week cycle). The starting dose was 15 mg/m2 of pralatrexate and 400 mg/m2 of gemcitabine.
BG001	Phase 1 - Group B	Phase 1 Treatment Group B had pralatrexate followed the next day by gemcitabine administered once every 2 weeks. One cycle of pralatrexate and gemcitabine was 4 weeks in duration and consisted of 2 doses each of pralatexate and gemcitabine. The starting dose was 10 mg/m2 of pralatrexate and 300 mg/m2 of gemcitabine.
BG002	Phase 1 - Group C	Phase 1 Treatment Group C had pralatrexate followed 1 hour later by gemcitabine administered once every 2 weeks. One cycle of pralatrexate and gemcitabine was 4 weeks in duration and consisted of 2 doses each of pralatrexate and gemcitabine. The starting dose was 10 mg/m2 of pralatrexate and 300 mg/m2 of gemcitabine.
BG003	Phase 2 - Group B	Phase 2 Treatment Group B had 10 mg/m2 of pralatrexate followed the next day by 400 mg/m2 of gemcitabine administered once every 2 weeks. One cycle of pralatrexate and gemcitabine was 4 weeks in duration and consisted of 2 doses each of pralatexate and gemcitabine.
BG004	Phase 2 - Group C	Phase 2 Treatment Group C had 15 mg/m2 of pralatrexate followed 1 hour later by 600 mg/m2 of gemcitabine administered once every 2 weeks. One cycle of pralatrexate and gemcitabine was 4 weeks in duration and consisted of 2 doses each of pralatrexate and gemcitabine.
BG005	Total	Total of all reporting groups

Units	Counts
Participants	BG0007 BG00110 BG00218 BG00338 BG00434 BG005107

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Objective Responses Assessed by International Workshop Criteria (IWC)

Number of participants who achieved an objective response. Objective response was defined as a tumor response assessment of either complete response (CR) or partial response (PR) and was determined only for patients with measurable disease at baseline. A tumor response assessment reported by IWC without PET was used for any analyses in cases where an IWC+PET evaluation was not done.

All patients who completed at least 1 cycle of treatment were included in the efficacy analysis

Posted

Number

participants

Assessed every 8 weeks (+/- 1 week) for Phase II and no less than every 3 cycles for Phase I

ID	Title	Description
OG000	Phase 1	Includes the Phase 1 dose-finding groups A, B, and C
OG001	Phase 2 - Group B	Phase 2 Treatment Group B had 10 mg/m2 of pralatrexate followed the next day by 400 mg/m2 of gemcitabine administered once every 2 weeks. One cycle of pralatrexate and gemcitabine was 4 weeks in duration and consisted of 2 doses each of pralatexate and gemcitabine.
OG002	Phase 2 - Group C	Phase 2 Treatment Group C had 15 mg/m2 of pralatrexate followed 1 hour later by 600 mg/m2 of gemcitabine administered once every 2 weeks. One cycle of pralatrexate and gemcitabine was 4 weeks in duration and consisted of 2 doses each of pralatrexate and gemcitabine.

Units	Counts
Participants	OG00034 OG00138 OG00234

Title

Denominators

Categories

Title	Measurements
	OG0008 OG0015 OG0027

Secondary

Duration of Response

Duration of response was defined as the number of days between the date of first tumor response assessment of objective response to the time of the first tumor response assessment of progressive disease (PD) or death due to any cause (date of first PD assessment or death - date of first objective response assessment + 1)

Posted

Median

Full Range

days

Response assessments were performed no less than every 3 cycles in the Phase 1 part of the study and every 8 weeks (± 1 week) in the Phase 2a part of the study

ID	Title	Description
OG000	Phase 1	Includes the Phase 1 dose-finding groups A, B, and C
OG001	Phase 2 - Group B	Phase 2 Treatment Group B had 10 mg/m2 of pralatrexate followed the next day by 400 mg/m2 of gemcitabine administered once every 2 weeks. One cycle of pralatrexate and gemcitabine was 4 weeks in duration and consisted of 2 doses each of pralatexate and gemcitabine.
OG002	Phase 2 - Group C	Phase 2 Treatment Group C had 15 mg/m2 of pralatrexate followed 1 hour later by 600 mg/m2 of gemcitabine administered once every 2 weeks. One cycle of pralatrexate and gemcitabine was 4 weeks in duration and consisted of 2 doses each of pralatrexate and gemcitabine.

Secondary

Progression-free Survival (PFS) Time

PFS time was calculated as the number of days from study day 1 to the date of PD or death, regardless of cause (date of PD or death - study day 1 + 1).

Posted

Median

95% Confidence Interval

days

Response assessments were performed no less than every 3 cycles in the Phase 1 part of the study and every 8 weeks (± 1 week) in the Phase 2a part of the study

ID	Title	Description
OG000	Phase 1	Includes the Phase 1 dose-finding groups A, B, and C
OG001	Phase 2 - Group B	Phase 2 Treatment Group B had 10 mg/m2 of pralatrexate followed the next day by 400 mg/m2 of gemcitabine administered once every 2 weeks. One cycle of pralatrexate and gemcitabine was 4 weeks in duration and consisted of 2 doses each of pralatexate and gemcitabine.
OG002	Phase 2 - Group C	Phase 2 Treatment Group C had 15 mg/m2 of pralatrexate followed 1 hour later by 600 mg/m2 of gemcitabine administered once every 2 weeks. One cycle of pralatrexate and gemcitabine was 4 weeks in duration and consisted of 2 doses each of pralatrexate and gemcitabine.

Serious Adverse Events

Term	Organ System	Statistical Information
altered state of consciousness	Nervous system disorders	EG0001 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
arrhythmia	Cardiac disorders	EG0001 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
cardiac failure congestive	Cardiac disorders	EG0001 affected35 at risk EG0011 affected38 at risk EG0021 affected34 at risk
cellulitis	Infections and infestations	EG0003 affected35 at risk EG0011 affected38 at risk EG0021 affected34 at risk
delirium tremens	Psychiatric disorders	EG0001 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
febrile neutropenia	Blood and lymphatic system disorders	EG0002 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
mental status changes	Psychiatric disorders	EG0001 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
myocardial infarction	Cardiac disorders	EG0002 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
pancytopenia	Blood and lymphatic system disorders	EG0001 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
pleural effusion	Respiratory, thoracic and mediastinal disorders	EG0001 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
pneumonia	Infections and infestations	EG0003 affected35 at risk EG0011 affected38 at risk EG0022 affected34 at risk
pneumonitis	Respiratory, thoracic and mediastinal disorders	EG0002 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
pulmonary embolism	Respiratory, thoracic and mediastinal disorders	EG0001 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
pyrexia	General disorders	EG0002 affected35 at risk EG0014 affected38 at risk EG0027 affected34 at risk
tachycardia	Cardiac disorders	EG0001 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
thrombocytopenia	Blood and lymphatic system disorders	EG0001 affected35 at risk EG0011 affected38 at risk EG0021 affected34 at risk
thrombophlebitis superficial	Vascular disorders	EG0001 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
upper airway obstruction	Respiratory, thoracic and mediastinal disorders	EG0001 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
weight decreased	Investigations	EG0001 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
sepsis	Infections and infestations	EG0000 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
anaemia	Blood and lymphatic system disorders	EG0000 affected35 at risk EG0012 affected38 at risk EG0020 affected34 at risk
chills	General disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0021 affected34 at risk
renal failure acute	Renal and urinary disorders	EG0000 affected35 at risk EG0012 affected38 at risk EG0022 affected34 at risk
fatigue	General disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
multi-organ failure	General disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
bacteraemia	Infections and infestations	EG0000 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
oral candidiasis	Infections and infestations	EG0000 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
respiratory syncytial virus infection	Infections and infestations	EG0000 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
sepsis syndrome	Infections and infestations	EG0000 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
dyspnoea	Respiratory, thoracic and mediastinal disorders	EG0000 affected35 at risk EG0010 affected38 at risk EG0024 affected34 at risk
hypoxia	Respiratory, thoracic and mediastinal disorders	EG0000 affected35 at risk EG0010 affected38 at risk EG0022 affected34 at risk
pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	EG0000 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
pleurisy	Respiratory, thoracic and mediastinal disorders	EG0000 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
neutropenia	Blood and lymphatic system disorders	EG0000 affected35 at risk EG0010 affected38 at risk EG0022 affected34 at risk
atrial flutter	Cardiac disorders	EG0000 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
bradycardia	Cardiac disorders	EG0000 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
cardio-respiratory arrest	Cardiac disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
diarrhoea	Gastrointestinal disorders	EG0000 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
oesophagitis	Gastrointestinal disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
stomatitis	Gastrointestinal disorders	EG0000 affected35 at risk EG0010 affected38 at risk EG0022 affected34 at risk
hydronephrosis	Renal and urinary disorders	EG0000 affected35 at risk EG0010 affected38 at risk EG0022 affected34 at risk
back pain	Musculoskeletal and connective tissue disorders	EG0000 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
muscular weakness	Musculoskeletal and connective tissue disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	EG0000 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
hypotension	Vascular disorders	EG0000 affected35 at risk EG0012 affected38 at risk EG0021 affected34 at risk
lymphoedema	Vascular disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
femoral neck fracture	Injury, poisoning and procedural complications	EG0000 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
dehydration	Metabolism and nutrition disorders	EG0000 affected35 at risk EG0010 affected38 at risk EG0022 affected34 at risk
cerebral haemorrhage	Nervous system disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
rash maculo-papular	Skin and subcutaneous tissue disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
asthenia	General disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
non-cardiac chest pain	General disorders	EG0000 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
pain	General disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
abdominal pain	Gastrointestinal disorders	EG0000 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
small intestinal obstruction	Gastrointestinal disorders	EG0000 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
electrolyte imbalance	Metabolism and nutrition disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
hyponatraemia	Metabolism and nutrition disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
hypovolaemia	Metabolism and nutrition disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
ventricular arrhythmia	Cardiac disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
urinary tract infection	Infections and infestations	EG0000 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
accidental overdose	Injury, poisoning and procedural complications	EG0000 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
tumor lysis syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	EG0000 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
skin exfoliation	Skin and subcutaneous tissue disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
pain management	Surgical and medical procedures	EG0000 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk

Other Adverse Events

Term	Organ System	Statistical Information
fatigue	General disorders	EG00025 affected35 at risk EG00118 affected38 at risk EG00215 affected34 at risk
pyrexia	General disorders	EG00023 affected35 at risk EG00118 affected38 at risk EG00215 affected34 at risk
chills	General disorders	EG0006 affected35 at risk EG00112 affected38 at risk EG0024 affected34 at risk
oedema peripheral	General disorders	EG0005 affected35 at risk EG0016 affected38 at risk EG0026 affected34 at risk
influenza like illness	General disorders	EG0003 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
asthenia	General disorders	EG0002 affected35 at risk EG0014 affected38 at risk EG0023 affected34 at risk
chest discomfort	General disorders	EG0002 affected35 at risk EG0011 affected38 at risk EG0021 affected34 at risk
chest pain	General disorders	EG0002 affected35 at risk EG0011 affected38 at risk EG0021 affected34 at risk
non-cardiac chest pain	General disorders	EG0002 affected35 at risk EG0010 affected38 at risk EG0023 affected34 at risk
stomatitis	Gastrointestinal disorders	EG00016 affected35 at risk EG0019 affected38 at risk EG00212 affected34 at risk
nausea	Gastrointestinal disorders	EG00015 affected35 at risk EG00124 affected38 at risk EG00221 affected34 at risk
diarrhoea	Gastrointestinal disorders	EG00013 affected35 at risk EG00111 affected38 at risk EG0028 affected34 at risk
vomiting	Gastrointestinal disorders	EG00012 affected35 at risk EG00110 affected38 at risk EG0029 affected34 at risk
constipation	Gastrointestinal disorders	EG00010 affected35 at risk EG00110 affected38 at risk EG00212 affected34 at risk
abdominal pain upper	Gastrointestinal disorders	EG0003 affected35 at risk EG0011 affected38 at risk EG0024 affected34 at risk
abdominal pain	Gastrointestinal disorders	EG0002 affected35 at risk EG0016 affected38 at risk EG0026 affected34 at risk
dysphagia	Gastrointestinal disorders	EG0002 affected35 at risk EG0012 affected38 at risk EG0021 affected34 at risk
epigastric discomfort	Gastrointestinal disorders	EG0002 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
gastrooesophageal reflux disease	Gastrointestinal disorders	EG0002 affected35 at risk EG0011 affected38 at risk EG0021 affected34 at risk
gingival pain	Gastrointestinal disorders	EG0002 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
glossodynia	Gastrointestinal disorders	EG0002 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
haematochezia	Gastrointestinal disorders	EG0002 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
oral pain	Gastrointestinal disorders	EG0002 affected35 at risk EG0013 affected38 at risk EG0022 affected34 at risk
anaemia	Blood and lymphatic system disorders	EG00019 affected35 at risk EG00114 affected38 at risk EG0029 affected34 at risk
neutropenia	Blood and lymphatic system disorders	EG00016 affected35 at risk EG00114 affected38 at risk EG0028 affected34 at risk
thrombocytopenia	Blood and lymphatic system disorders	EG00014 affected35 at risk EG00116 affected38 at risk EG0028 affected34 at risk
leukopenia	Blood and lymphatic system disorders	EG0005 affected35 at risk EG0014 affected38 at risk EG0023 affected34 at risk
febrile neutropenia	Blood and lymphatic system disorders	EG0003 affected35 at risk EG0012 affected38 at risk EG0021 affected34 at risk
lymphopenia	Blood and lymphatic system disorders	EG0002 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
pancytopenia	Blood and lymphatic system disorders	EG0002 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
dyspnoea	Respiratory, thoracic and mediastinal disorders	EG0007 affected35 at risk EG0015 affected38 at risk EG0029 affected34 at risk
epistaxis	Respiratory, thoracic and mediastinal disorders	EG0007 affected35 at risk EG0012 affected38 at risk EG0022 affected34 at risk
cough	Respiratory, thoracic and mediastinal disorders	EG0006 affected35 at risk EG0018 affected38 at risk EG0022 affected34 at risk
wheezing	Respiratory, thoracic and mediastinal disorders	EG0005 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
hypoxia	Respiratory, thoracic and mediastinal disorders	EG0004 affected35 at risk EG0012 affected38 at risk EG0024 affected34 at risk
pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	EG0004 affected35 at risk EG0016 affected38 at risk EG0024 affected34 at risk
pleural effusion	Respiratory, thoracic and mediastinal disorders	EG0004 affected35 at risk EG0012 affected38 at risk EG0021 affected34 at risk
dysphonia	Respiratory, thoracic and mediastinal disorders	EG0003 affected35 at risk EG0012 affected38 at risk EG0020 affected34 at risk
productive cough	Respiratory, thoracic and mediastinal disorders	EG0003 affected35 at risk EG0012 affected38 at risk EG0020 affected34 at risk
pleuritic pain	Respiratory, thoracic and mediastinal disorders	EG0002 affected35 at risk EG0011 affected38 at risk EG0021 affected34 at risk
pneumonitis	Respiratory, thoracic and mediastinal disorders	EG0002 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
rhinitis allergic	Respiratory, thoracic and mediastinal disorders	EG0002 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
cellulitis	Infections and infestations	EG0004 affected35 at risk EG0011 affected38 at risk EG0020 affected34 at risk
pneumonia	Infections and infestations	EG0004 affected35 at risk EG0012 affected38 at risk EG0023 affected34 at risk
oral candidiasis	Infections and infestations	EG0002 affected35 at risk EG0012 affected38 at risk EG0022 affected34 at risk
upper respiratory tract infection	Infections and infestations	EG0002 affected35 at risk EG0013 affected38 at risk EG0023 affected34 at risk
dizziness	Nervous system disorders	EG0008 affected35 at risk EG0015 affected38 at risk EG0028 affected34 at risk
paraesthesia	Nervous system disorders	EG0008 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
headache	Nervous system disorders	EG0007 affected35 at risk EG0019 affected38 at risk EG0026 affected34 at risk
neuropathy peripheral	Nervous system disorders	EG0004 affected35 at risk EG0013 affected38 at risk EG0022 affected34 at risk
hypoaesthesia	Nervous system disorders	EG0002 affected35 at risk EG0012 affected38 at risk EG0022 affected34 at risk
alanine aminotransferase increased	Investigations	EG0004 affected35 at risk EG0013 affected38 at risk EG0024 affected34 at risk
alanine aminotransferase	Investigations	EG0002 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
aspartate aminotransferase increased	Investigations	EG0002 affected35 at risk EG0013 affected38 at risk EG0022 affected34 at risk
blood creatinine increased	Investigations	EG0002 affected35 at risk EG0012 affected38 at risk EG0022 affected34 at risk
cardiac murmur	Investigations	EG0002 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
platelet count decreased	Investigations	EG0002 affected35 at risk EG0011 affected38 at risk EG0022 affected34 at risk
weight decreased	Investigations	EG0002 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
white blood cell count	Investigations	EG0002 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
rash	Skin and subcutaneous tissue disorders	EG0005 affected35 at risk EG0012 affected38 at risk EG0022 affected34 at risk
alopecia	Skin and subcutaneous tissue disorders	EG0004 affected35 at risk EG0012 affected38 at risk EG0020 affected34 at risk
pruritus	Skin and subcutaneous tissue disorders	EG0004 affected35 at risk EG0015 affected38 at risk EG0025 affected34 at risk
erythema	Skin and subcutaneous tissue disorders	EG0003 affected35 at risk EG0012 affected38 at risk EG0022 affected34 at risk
night sweats	Skin and subcutaneous tissue disorders	EG0003 affected35 at risk EG0015 affected38 at risk EG0022 affected34 at risk
swelling face	Skin and subcutaneous tissue disorders	EG0002 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
back pain	Musculoskeletal and connective tissue disorders	EG0005 affected35 at risk EG0014 affected38 at risk EG0023 affected34 at risk
muscular weakness	Musculoskeletal and connective tissue disorders	EG0004 affected35 at risk EG0012 affected38 at risk EG0020 affected34 at risk
neck pain	Musculoskeletal and connective tissue disorders	EG0003 affected35 at risk EG0014 affected38 at risk EG0022 affected34 at risk
myalgia	Musculoskeletal and connective tissue disorders	EG0002 affected35 at risk EG0011 affected38 at risk EG0024 affected34 at risk
hypotension	Vascular disorders	EG0006 affected35 at risk EG0013 affected38 at risk EG0023 affected34 at risk
flushing	Vascular disorders	EG0002 affected35 at risk EG0011 affected38 at risk EG0022 affected34 at risk
hypertension	Vascular disorders	EG0002 affected35 at risk EG0011 affected38 at risk EG0021 affected34 at risk
decreased appetite	Metabolism and nutrition disorders	EG0005 affected35 at risk EG0013 affected38 at risk EG0021 affected34 at risk
anorexia	Metabolism and nutrition disorders	EG0003 affected35 at risk EG0017 affected38 at risk EG0025 affected34 at risk
hyperuricaemia	Metabolism and nutrition disorders	EG0002 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
palpitations	Cardiac disorders	EG0004 affected35 at risk EG0010 affected38 at risk EG0021 affected34 at risk
tachycardia	Cardiac disorders	EG0003 affected35 at risk EG0013 affected38 at risk EG0022 affected34 at risk
myocardial infarction	Cardiac disorders	EG0002 affected35 at risk EG0010 affected38 at risk EG0020 affected34 at risk
anxiety	Psychiatric disorders	EG0003 affected35 at risk EG0013 affected38 at risk EG0021 affected34 at risk
abdominal discomfort	Gastrointestinal disorders	EG0001 affected35 at risk EG0010 affected38 at risk EG0023 affected34 at risk
lip pain	Gastrointestinal disorders	EG0000 affected35 at risk EG0012 affected38 at risk EG0020 affected34 at risk
pain	General disorders	EG0001 affected35 at risk EG0012 affected38 at risk EG0024 affected34 at risk
memory impairment	Nervous system disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0022 affected34 at risk
arthralgia	Musculoskeletal and connective tissue disorders	EG0001 affected35 at risk EG0013 affected38 at risk EG0022 affected34 at risk
bone pain	Musculoskeletal and connective tissue disorders	EG0001 affected35 at risk EG0010 affected38 at risk EG0022 affected34 at risk
muscle spasms	Musculoskeletal and connective tissue disorders	EG0001 affected35 at risk EG0013 affected38 at risk EG0020 affected34 at risk
pain in extremity	Musculoskeletal and connective tissue disorders	EG0001 affected35 at risk EG0014 affected38 at risk EG0026 affected34 at risk
rash pruritic	Skin and subcutaneous tissue disorders	EG0000 affected35 at risk EG0017 affected38 at risk EG0021 affected34 at risk
rash erythematous	Skin and subcutaneous tissue disorders	EG0000 affected35 at risk EG0012 affected38 at risk EG0020 affected34 at risk
rash maculo-papular	Skin and subcutaneous tissue disorders	EG0000 affected35 at risk EG0012 affected38 at risk EG0020 affected34 at risk
skin lesion	Skin and subcutaneous tissue disorders	EG0001 affected35 at risk EG0011 affected38 at risk EG0022 affected34 at risk
dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	EG0001 affected35 at risk EG0013 affected38 at risk EG0020 affected34 at risk
nasal congestion	Respiratory, thoracic and mediastinal disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0022 affected34 at risk
haemoptysis	Respiratory, thoracic and mediastinal disorders	EG0001 affected35 at risk EG0013 affected38 at risk EG0021 affected34 at risk
rales	Respiratory, thoracic and mediastinal disorders	EG0000 affected35 at risk EG0012 affected38 at risk EG0021 affected34 at risk
neutrophil count decreased	Investigations	EG0001 affected35 at risk EG0016 affected38 at risk EG0022 affected34 at risk
weight increased	Investigations	EG0000 affected35 at risk EG0012 affected38 at risk EG0021 affected34 at risk
sepsis syndrome	Infections and infestations	EG0000 affected35 at risk EG0012 affected38 at risk EG0020 affected34 at risk
dehydration	Metabolism and nutrition disorders	EG0001 affected35 at risk EG0011 affected38 at risk EG0023 affected34 at risk
hypocalcaemia	Metabolism and nutrition disorders	EG0000 affected35 at risk EG0012 affected38 at risk EG0020 affected34 at risk
hypokalaemia	Metabolism and nutrition disorders	EG0001 affected35 at risk EG0011 affected38 at risk EG0025 affected34 at risk
hypomagnesaemia	Metabolism and nutrition disorders	EG0000 affected35 at risk EG0012 affected38 at risk EG0023 affected34 at risk
lacrimation increased	Eye disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0022 affected34 at risk
renal failure acute	Renal and urinary disorders	EG0000 affected35 at risk EG0012 affected38 at risk EG0023 affected34 at risk
ear pain	Ear and labyrinth disorders	EG0000 affected35 at risk EG0013 affected38 at risk EG0021 affected34 at risk
musculoskeletal pain	Musculoskeletal and connective tissue disorders	EG0003 affected35 at risk EG0011 affected38 at risk EG0023 affected34 at risk
catheter site pain	General disorders	EG0000 affected35 at risk EG0012 affected38 at risk EG0020 affected34 at risk
pitting oedema	General disorders	EG0000 affected35 at risk EG0012 affected38 at risk EG0020 affected34 at risk
groin pain	Musculoskeletal and connective tissue disorders	EG0000 affected35 at risk EG0012 affected38 at risk EG0020 affected34 at risk
musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	EG0001 affected35 at risk EG0010 affected38 at risk EG0022 affected34 at risk
dysgeusia	Nervous system disorders	EG0000 affected35 at risk EG0012 affected38 at risk EG0021 affected34 at risk
urticaria	Skin and subcutaneous tissue disorders	EG0001 affected35 at risk EG0010 affected38 at risk EG0022 affected34 at risk
white blood cell count decreased	Investigations	EG0001 affected35 at risk EG0013 affected38 at risk EG0021 affected34 at risk
blood lactate dehydrogenase increased	Investigations	EG0000 affected35 at risk EG0012 affected38 at risk EG0020 affected34 at risk
sinus tachycardia	Cardiac disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0022 affected34 at risk
bradycardia	Cardiac disorders	EG0001 affected35 at risk EG0010 affected38 at risk EG0022 affected34 at risk
hydronephrosis	Renal and urinary disorders	EG0001 affected35 at risk EG0010 affected38 at risk EG0022 affected34 at risk
incontinence	Renal and urinary disorders	EG0000 affected35 at risk EG0012 affected38 at risk EG0020 affected34 at risk
insomnia	Psychiatric disorders	EG0001 affected35 at risk EG0011 affected38 at risk EG0023 affected34 at risk
confusional state	Psychiatric disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0022 affected34 at risk
vision blurred	Eye disorders	EG0001 affected35 at risk EG0011 affected38 at risk EG0023 affected34 at risk
ocular hyperaemia	Eye disorders	EG0001 affected35 at risk EG0010 affected38 at risk EG0022 affected34 at risk
urinary tract infection	Infections and infestations	EG0003 affected35 at risk EG0011 affected38 at risk EG0022 affected34 at risk
haemoglobin decreased	Investigations	EG0001 affected35 at risk EG0015 affected38 at risk EG0020 affected34 at risk
hyperglycaemia	Metabolism and nutrition disorders	EG0000 affected35 at risk EG0011 affected38 at risk EG0022 affected34 at risk
hypoglycaemia	Metabolism and nutrition disorders	EG0000 affected35 at risk EG0010 affected38 at risk EG0022 affected34 at risk
hyponatraemia	Metabolism and nutrition disorders	EG0001 affected35 at risk EG0014 affected38 at risk EG0020 affected34 at risk

ID	Term
D012008	Recurrence
D006689	Hodgkin Disease
D016411	Lymphoma, T-Cell, Peripheral
D016393	Lymphoma, B-Cell
D008258	Waldenstrom Macroglobulinemia
D008223	Lymphoma
D008228	Lymphoma, Non-Hodgkin
D016399	Lymphoma, T-Cell
D007938	Leukemia
D007119	Immunoblastic Lymphadenopathy
D017728	Lymphoma, Large-Cell, Anaplastic
D054391	Lymphoma, Extranodal NK-T-Cell

ID	Term
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D054219	Neoplasms, Plasma Cell
D020141	Hemostatic Disorders
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D010265	Paraproteinemias
D001796	Blood Protein Disorders
D006402	Hematologic Diseases
D006474	Hemorrhagic Disorders
D000072281	Lymphadenopathy

ID	Term
C418863	10-propargyl-10-deazaaminopterin
D000093542	Gemcitabine
D003132	Commerce
D000074584	WW Domain-Containing Oxidoreductase
D014805	Vitamin B 12
D005492	Folic Acid

ID	Term
D006571	Heterocyclic Compounds
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D013676	Technology, Industry, and Agriculture
D000074583	Short Chain Dehydrogenase-Reductases
D064430	NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases
D000429	Alcohol Oxidoreductases
D010088	Oxidoreductases
D004798	Enzymes
D045762	Enzymes and Coenzymes
D025521	Tumor Suppressor Proteins
D009363	Neoplasm Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D045728	Corrinoids
D045725	Tetrapyrroles
D011758	Pyrroles
D001393	Azoles
D006576	Heterocyclic Compounds, 4 or More Rings
D000072471	Heterocyclic Compounds, Fused-Ring
D047028	Macrocyclic Compounds
D011083	Polycyclic Compounds
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 1	Patients that received at least one dose of pralatrexate in the Phase 1 portion of the study	18	35	35	35
EG001	Phase 2 - Group B	Phase 2 Treatment Group B had 10 mg/m2 of pralatrexate followed the next day by 400 mg/m2 of gemcitabine administered once every 2 weeks. One cycle of pralatrexate and gemcitabine was 4 weeks in duration and consisted of 2 doses each of pralatexate and gemcitabine.	13	38	38	38
EG002	Phase 2 - Group C	Phase 2 Treatment Group C had 15 mg/m2 of pralatrexate followed 1 hour later by 600 mg/m2 of gemcitabine administered once every 2 weeks. One cycle of pralatrexate and gemcitabine was 4 weeks in duration and consisted of 2 doses each of pralatrexate and gemcitabine.	16	34	34	34