Study of Pralatrexate to Treat Participants With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

• Sponsor: Spectrum Pharmaceuticals, Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00998946
• Collaborator: (none)
• Enrollment: 29
• Locations: 11
• Arm: 1
• Actual Duration (Months): 35
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether pralatrexate, given with vitamin B12 and folic acid, is effective in the treatment of relapsed or refractory B-cell Non-Hodgkin's lymphoma (NHL). The study will also investigate the safety of pralatrexate with vitamin B12 and folic acid in this participant population. Additionally, this study includes the collection of blood samples to investigate the pharmacokinetics (PK) of pralatrexate in this participant population (PK is the activity of a drug in the body over a period of time, including how the drug is absorbed, distributed in the body, localized in the tissues, and excreted from the body).

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, B-Cell	Drug: Pralatrexate; Dietary Supplement: Vitamin B12; Dietary Supplement: Folic Acid	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Single-arm, Open-label, Multi-center Study of Pralatrexate in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
• Actual Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Pralatrexate Participants received pralatrexate at an initial dose of 30 mg/m^2, as IV push over 30 seconds to 5 minutes via a patent free-flowing IV line containing normal saline on Days 1, 8 and 15 of a 4-week cycle (weekly for 3 weeks with 1 week of rest) until criteria for discontinuation per protocol were met. The initial dose of 30 mg/m^2 may be reduced to 20 mg/m^2 weekly, permitted per protocol defined criteria. If pralatrexate 20 mg/m^2/week was not tolerated, pralatrexate had to be discontinued. Dose re-escalation was not allowed once dose reduction was done. Participants had dietary supplement of vitamin B12 and folic acid along with pralatrexate. Vitamin B12, given as 1mg IM, within 10 weeks of start of pralatrexate dosing, every 8-10 weeks throughout the study and for at least 30 days post last dose of pralatrexate. Folic acid was given 1mg daily, orally, for at least 7 days prior to start of pralatrexate, throughout the study and for at least 30 days post last dose of pralatrexate.

Drug: Pralatrexate; Pralatrexate injection administered as intravenous (IV) push; Other Names: FOLOTYN PDX (RS)-10-propargyl-10-deazaaminopterin ; Dietary Supplement: Vitamin B12; 1 mg intramuscular (IM) injection; Other Names: Cyanocobalamin ; Dietary Supplement: Folic Acid; Oral 1 mg tablet; Other Names: Vitamin B9 Folate Folacin

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) [Up to 24 months]

   Objective response rate was defined as the percentage of participants with a complete response (CR) or a partial response (PR). Tumor response was evaluated on the basis of clinical and radiological criteria, assessed according to International Workshop Criteria (IWC) with or without positron emission tomography (PET) scans. Per IWC criteria CR is defined as complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities definitely assignable to non-Hodgkin's lymphoma (NHL) and PR is defined as >= 50% decrease in sum of the product of the perpendicular diameters (SPD) of the six largest dominant nodes or nodal masses and no increase in size of other nodes, liver or spleen.

Secondary Outcome Measures

1. Duration of Response (DOR) [Up to 24 months]

   The Duration of Response was defined as the time (in months) from the date the measurement criteria were first met for CR or PR (whichever status was recorded first) until the first subsequent date that relapse or progression was documented. It was assessed according to IWC with or without PET, subject to its availability. Per IWC, progression was defined as a ≥50% increase from the nadir in the individual sum of the products of the diameters of any index lesion; the reappearance of pathology, enlargement of liver/spleen, or unequivocal progression of non-measurable disease or appearance of any new lesions.

2. Progression Free Survival (PFS) [Up to 24 months]

   Progression-free survival (PFS) was the duration of time (in months) from first administration of study treatment to date of first documented progression or death from any cause. It was based on tumor assessments made according to the IWC with or without PET scans, subject to their availability. Per IWC, progression was defined as a ≥50% increase from the nadir in the individual sum of the products of the diameters of any index lesion; the reappearance of pathology, enlargement of liver/spleen, or unequivocal progression of non-measurable disease or appearance of any new lesions.

3. Overall Survival (OS) [Up to 24 months]

   Overall Survival was the time (in months) from first administration of study treatment until the date of death.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically/cytologically confirmed, measurable (lesion or node =2 cm by CT [at least 1 cm if by spiral CT]) B-cell Non-Hodgkin's Lymphoma, using the Revised European American Lymphoma (REAL) World Health Organization (WHO) disease classification

• Progressive or persistent disease after ≥ 1 prior treatment(s)

• Recovered from toxic effects of prior treatment

• At least 4 weeks since most recent cytotoxic therapy

• Easter Cooperative Oncology Group (ECOG) performance status ≤ 2

• Adequate blood, liver, and kidney functions as defined by laboratory levels

• 1.0 mg/day orally of folic acid for at least 7 days prior & 1 mg intramuscular of vitamin B12 within 10 weeks of the planned start of pralatrexate

• Females of childbearing potential must agree to use medically acceptable birth control from start of pralatrexate until at least 30 days after the last administration of pralatrexate and must have a negative serum pregnancy test within 14 days prior to the first day of study treatment

• Males who are not surgically sterile must agree to use medically acceptable birth control from start of pralatrexate until at least 90 days after the last administration of pralatrexate

• Available for repeat dosing and follow-up

• Able to give written informed consent

Exclusion Criteria:

• Relapsed participants with diffuse large B-cell lymphoma (DLBCL) who are candidates for high-dose therapy and autologous stem cell transplantation (SCT) and for whom high-dose therapy and autologous SCT 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 malignancies other than those exceptions listed above, the participant must be disease-free for ≥ 5 years. Participants with other prior malignancies < 5 years before study entry may still be enrolled if they have received treatment resulting in complete resolution of the cancer and currently have no clinical, radiologic, or laboratory evidence of active or recurrent disease

• Congestive heart failure Class III/IV according to the New York Heart Association Functional Classification

• Uncontrolled hypertension

• Known human immunodeficiency virus (HIV)-positive diagnosis

• Symptomatic central nervous system (CNS) metastases or lesions for which treatment is required. Participants who received prophylactic CNS treatment are eligible.

• Participants who have undergone an allogeneic SCT

• Participants who have relapsed < 100 days from the time of an autologous SCT

• Participants with disease refractory to peripheral blood SCT or who have relapsed < 100 days from the time of transplant

• Active uncontrolled infection, underlying medical condition, or other serious illness that would impair the ability of the participant to receive protocol treatment.

• Major surgery within 14 days of enrollment

• Receipt of any conventional chemotherapy or radiation therapy (encompassing a substantial [> 10%] amount of bone marrow) within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study treatment or planned use during the course of the study

• Receipt of systemic corticosteroids within 1 week of study treatment, unless participant has been taking a continuous dose of no more than 10 mg/day of prednisone or its equivalent for at least 1 month

• Use of any investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the course of the study

• Previous exposure to pralatrexate

• Females who are pregnant or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tower Cancer Research Foundation	Beverly Hills	California	United States	90211
2	Kootenai Cancer Center	Post Falls	Idaho	United States	83854
3	Rush University Medical Center	Chicago	Illinois	United States	60612
4	Owsley Brown Frazier Cancer Center	Louisville	Kentucky	United States	40245
5	Overton Brooks VA Medical Center	Shreveport	Louisiana	United States	71101
6	Frontier Cancer Center and Blood Institute	Billings	Montana	United States	59102
7	New York University Hospital	New York	New York	United States	10016
8	Providence Cancer Center	Portland	Oregon	United States	97225
9	The West Clinic (ACORN)	Memphis	Tennessee	United States	38120
10	Gundersen Lutheran	La Crosse	Wisconsin	United States	54601
11	University of Wisconsin, Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53705-2275

Sponsors and Collaborators

• Spectrum Pharmaceuticals, Inc

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Spectrum Pharmaceuticals, Inc
• ClinicalTrials.gov Identifier: NCT00998946
• Other Study ID Numbers: PDX-015
• First Posted: Oct 21, 2009
• Last Update Posted: Nov 5, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Spectrum Pharmaceuticals, Inc: Relapsed; Refractory; Non-Hodgkin's
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Vitamins; Folic Acid; Vitamin B 12; Hydroxocobalamin; Vitamin B Complex; 10-deazaaminopterin

Study Results

Participant Flow

Arm/Group Title	Pralatrexate
Arm/Group Description	Participants received pralatrexate at an initial dose of 30 mg/m^2, as IV push over 30 seconds to 5 minutes via a patent free-flowing IV line containing normal saline on Days 1, 8 and 15 of a 4-week cycle (weekly for 3 weeks with 1 week of rest) until criteria for discontinuation per protocol were met. The initial dose of 30 mg/m^2 may be reduced to 20 mg/m^2 weekly, permitted per protocol defined criteria. If pralatrexate 20 mg/m^2/week was not tolerated, pralatrexate had to be discontinued. Dose re-escalation was not allowed once dose reduction was done. Participants had dietary supplement of vitamin B12 and folic acid along with pralatrexate. Vitamin B12, given as 1mg IM, within 10 weeks of start of pralatrexate dosing, every 8-10 weeks throughout the study and for at least 30 days post last dose of pralatrexate. Folic acid was given 1mg daily, orally, for at least 7 days prior to start of pralatrexate, throughout the study and for at least 30 days post last dose of pralatrexate.
Period Title: Overall Study
STARTED	29
Safety Population	27
COMPLETED	20
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	Pralatrexate
Arm/Group Description	Participants received pralatrexate at an initial dose of 30 mg/m^2, as IV push over 30 seconds to 5 minutes via a patent free-flowing IV line containing normal saline on Days 1, 8 and 15 of a 4-week cycle (weekly for 3 weeks with 1 week of rest) until criteria for discontinuation per protocol were met. The initial dose of 30 mg/m^2 may be reduced to 20 mg/m^2 weekly, permitted per protocol defined criteria. If pralatrexate 20 mg/m^2/week was not tolerated, pralatrexate had to be discontinued. Dose re-escalation was not allowed once dose reduction was done. Participants had dietary supplement of vitamin B12 and folic acid along with pralatrexate. Vitamin B12, given as 1mg IM, within 10 weeks of start of pralatrexate dosing, every 8-10 weeks throughout the study and for at least 30 days post last dose of pralatrexate. Folic acid was given 1mg daily, orally, for at least 7 days prior to start of pralatrexate, throughout the study and for at least 30 days post last dose of pralatrexate.
Overall Participants	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.8 (14.07)
Sex: Female, Male (Count of Participants)
Female	7 25.9%
Male	20 74.1%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	Objective response rate was defined as the percentage of participants with a complete response (CR) or a partial response (PR). Tumor response was evaluated on the basis of clinical and radiological criteria, assessed according to International Workshop Criteria (IWC) with or without positron emission tomography (PET) scans. Per IWC criteria CR is defined as complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities definitely assignable to non-Hodgkin's lymphoma (NHL) and PR is defined as >= 50% decrease in sum of the product of the perpendicular diameters (SPD) of the six largest dominant nodes or nodal masses and no increase in size of other nodes, liver or spleen.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

Efficacy Evaluable Population included participants who received at least 1 dose of protocol specified treatment and had measurable disease at baseline to be considered evaluable.

Arm/Group Title	Pralatrexate
Arm/Group Description	Participants received pralatrexate at an initial dose of 30 mg/m^2, as IV push over 30 seconds to 5 minutes via a patent free-flowing IV line containing normal saline on Days 1, 8 and 15 of a 4-week cycle (weekly for 3 weeks with 1 week of rest) until criteria for discontinuation per protocol were met. The initial dose of 30 mg/m^2 may be reduced to 20 mg/m^2 weekly, permitted per protocol defined criteria. If pralatrexate 20 mg/m^2/week was not tolerated, pralatrexate had to be discontinued. Dose re-escalation was not allowed once dose reduction was done. Participants had dietary supplement of vitamin B12 and folic acid along with pralatrexate. Vitamin B12, given as 1mg IM, within 10 weeks of start of pralatrexate dosing, every 8-10 weeks throughout the study and for at least 30 days post last dose of pralatrexate. Folic acid was given 1mg daily, orally, for at least 7 days prior to start of pralatrexate, throughout the study and for at least 30 days post last dose of pralatrexate.
Measure Participants	27
Number (95% Confidence Interval) [percentage of participants]	4 14.8%

2. Secondary Outcome

Title	Duration of Response (DOR)
Description	The Duration of Response was defined as the time (in months) from the date the measurement criteria were first met for CR or PR (whichever status was recorded first) until the first subsequent date that relapse or progression was documented. It was assessed according to IWC with or without PET, subject to its availability. Per IWC, progression was defined as a ≥50% increase from the nadir in the individual sum of the products of the diameters of any index lesion; the reappearance of pathology, enlargement of liver/spleen, or unequivocal progression of non-measurable disease or appearance of any new lesions.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

Efficacy Evaluable Population included participants who received at least 1 dose of protocol specified treatment and had measurable disease at baseline to be considered evaluable.

Arm/Group Title	Pralatrexate
Arm/Group Description	Participants received pralatrexate at an initial dose of 30 mg/m^2, as IV push over 30 seconds to 5 minutes via a patent free-flowing IV line containing normal saline on Days 1, 8 and 15 of a 4-week cycle (weekly for 3 weeks with 1 week of rest) until criteria for discontinuation per protocol were met. The initial dose of 30 mg/m^2 may be reduced to 20 mg/m^2 weekly, permitted per protocol defined criteria. If pralatrexate 20 mg/m^2/week was not tolerated, pralatrexate had to be discontinued. Dose re-escalation was not allowed once dose reduction was done. Participants had dietary supplement of vitamin B12 and folic acid along with pralatrexate. Vitamin B12, given as 1mg IM, within 10 weeks of start of pralatrexate dosing, every 8-10 weeks throughout the study and for at least 30 days post last dose of pralatrexate. Folic acid was given 1mg daily, orally, for at least 7 days prior to start of pralatrexate, throughout the study and for at least 30 days post last dose of pralatrexate.
Measure Participants	27
Median (95% Confidence Interval) [months]	NA

3. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Progression-free survival (PFS) was the duration of time (in months) from first administration of study treatment to date of first documented progression or death from any cause. It was based on tumor assessments made according to the IWC with or without PET scans, subject to their availability. Per IWC, progression was defined as a ≥50% increase from the nadir in the individual sum of the products of the diameters of any index lesion; the reappearance of pathology, enlargement of liver/spleen, or unequivocal progression of non-measurable disease or appearance of any new lesions.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

Efficacy Evaluable Population included participants who received at least 1 dose of protocol specified treatment and had measurable disease at baseline to be considered evaluable.

Arm/Group Title	Pralatrexate
Arm/Group Description	Participants received pralatrexate at an initial dose of 30 mg/m^2, as IV push over 30 seconds to 5 minutes via a patent free-flowing IV line containing normal saline on Days 1, 8 and 15 of a 4-week cycle (weekly for 3 weeks with 1 week of rest) until criteria for discontinuation per protocol were met. The initial dose of 30 mg/m^2 may be reduced to 20 mg/m^2 weekly, permitted per protocol defined criteria. If pralatrexate 20 mg/m^2/week was not tolerated, pralatrexate had to be discontinued. Dose re-escalation was not allowed once dose reduction was done. Participants had dietary supplement of vitamin B12 and folic acid along with pralatrexate. Vitamin B12, given as 1mg IM, within 10 weeks of start of pralatrexate dosing, every 8-10 weeks throughout the study and for at least 30 days post last dose of pralatrexate. Folic acid was given 1mg daily, orally, for at least 7 days prior to start of pralatrexate, throughout the study and for at least 30 days post last dose of pralatrexate.
Measure Participants	27
Median (95% Confidence Interval) [months]	3.6

4. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall Survival was the time (in months) from first administration of study treatment until the date of death.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

Efficacy Evaluable Population included participants who received at least 1 dose of protocol specified treatment and had measurable disease at baseline to be considered evaluable.

Arm/Group Title	Pralatrexate
Arm/Group Description	Participants received pralatrexate at an initial dose of 30 mg/m^2, as IV push over 30 seconds to 5 minutes via a patent free-flowing IV line containing normal saline on Days 1, 8 and 15 of a 4-week cycle (weekly for 3 weeks with 1 week of rest) until criteria for discontinuation per protocol were met. The initial dose of 30 mg/m^2 may be reduced to 20 mg/m^2 weekly, permitted per protocol defined criteria. If pralatrexate 20 mg/m^2/week was not tolerated, pralatrexate had to be discontinued. Dose re-escalation was not allowed once dose reduction was done. Participants had dietary supplement of vitamin B12 and folic acid along with pralatrexate. Vitamin B12, given as 1mg IM, within 10 weeks of start of pralatrexate dosing, every 8-10 weeks throughout the study and for at least 30 days post last dose of pralatrexate. Folic acid was given 1mg daily, orally, for at least 7 days prior to start of pralatrexate, throughout the study and for at least 30 days post last dose of pralatrexate.
Measure Participants	27
Median (95% Confidence Interval) [months]	NA

Adverse Events

Time Frame	Up to 24 months
Adverse Event Reporting Description	Safety Population included all participants who received at least 1 dose of study drug.
Arm/Group Title	Pralatrexate
Arm/Group Description	Participants received pralatrexate at an initial dose of 30 mg/m^2, as IV push over 30 seconds to 5 minutes via a patent free-flowing IV line containing normal saline on Days 1, 8 and 15 of a 4-week cycle (weekly for 3 weeks with 1 week of rest) until criteria for discontinuation per protocol were met. The initial dose of 30 mg/m^2 may be reduced to 20 mg/m^2 weekly, permitted per protocol defined criteria. If pralatrexate 20 mg/m^2/week was not tolerated, pralatrexate had to be discontinued. Dose re-escalation was not allowed once dose reduction was done. Participants had dietary supplement of vitamin B12 and folic acid along with pralatrexate. Vitamin B12, given as 1mg IM, within 10 weeks of start of pralatrexate dosing, every 8-10 weeks throughout the study and for at least 30 days post last dose of pralatrexate. Folic acid was given 1mg daily, orally, for at least 7 days prior to start of pralatrexate, throughout the study and for at least 30 days post last dose of pralatrexate.
All Cause Mortality
	Pralatrexate
	Affected / at Risk (%)	# Events
Total	11/27 (40.7%)
Serious Adverse Events
	Pralatrexate
	Affected / at Risk (%)	# Events
Total	11/27 (40.7%)
Blood and lymphatic system disorders
Febrile Neutropenia	1/27 (3.7%)
Neutopenia	1/27 (3.7%)
Cardiac disorders
Atrial fibrillation	1/27 (3.7%)
Cardiac Failure Congestive	1/27 (3.7%)
Ear and labyrinth disorders
Ear Pain	1/27 (3.7%)
Gastrointestinal disorders
Diarrhoea	1/27 (3.7%)
Dysphagia	1/27 (3.7%)
Oesophagitis	1/27 (3.7%)
Stomatitis	5/27 (18.5%)
General disorders
Pyrexia	2/27 (7.4%)
Infections and infestations
Catheter Related Infection	1/27 (3.7%)
Cellulitis	1/27 (3.7%)
Pneumonia	2/27 (7.4%)
Sinusitis	1/27 (3.7%)
Metabolism and nutrition disorders
Dehydration	1/27 (3.7%)
Failure To Thrive	1/27 (3.7%)
Hypercalcemia	1/27 (3.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm Progression	2/27 (7.4%)
Nervous system disorders
Sinus Headache	1/27 (3.7%)
Psychiatric disorders
Mental Status Changes	1/27 (3.7%)
Renal and urinary disorders
Haematuria	1/27 (3.7%)
Respiratory, thoracic and mediastinal disorders
Laryngeal Inflammation	1/27 (3.7%)
Pharyngeal Inflammation	1/27 (3.7%)
Pleural Effusion	1/27 (3.7%)
Skin and subcutaneous tissue disorders
Rash Maculo-Papular	1/27 (3.7%)
Other (Not Including Serious) Adverse Events
	Pralatrexate
	Affected / at Risk (%)	# Events
Total	27/27 (100%)
Blood and lymphatic system disorders
Neutropenia	7/27 (25.9%)
Anaemia	11/27 (40.7%)
Lymphadenopathy	1/27 (3.7%)
Leukopenia	4/27 (14.8%)
Thrombocytopenia	13/27 (48.1%)
Cardiac disorders
Atrial fibrillation	1/27 (3.7%)
Sinus tachycardia	1/27 (3.7%)
Supraventricular tachycardia	1/27 (3.7%)
Ear and labyrinth disorders
Ear pain	1/27 (3.7%)
Eye disorders
Dry eye	2/27 (7.4%)
Vision blurred	1/27 (3.7%)
Gastrointestinal disorders
Abdominal distension	2/27 (7.4%)
Abdominal pain	6/27 (22.2%)
Abdominal tenderness	1/27 (3.7%)
Consitpation	7/27 (25.9%)
Diarrhoea	7/27 (25.9%)
Dyspepsia	1/27 (3.7%)
Dysphagia	1/27 (3.7%)
Gastrooesophageal reflux disease	1/27 (3.7%)
Gingival pain	1/27 (3.7%)
Haematochezia	1/27 (3.7%)
Haemorrhoids	1/27 (3.7%)
Mouth ulceration	2/27 (7.4%)
Nausea	12/27 (44.4%)
Odynophagia	1/27 (3.7%)
Oesophagitis	1/27 (3.7%)
Oral discomfort	1/27 (3.7%)
Oral pain	2/27 (7.4%)
Proctitis	1/27 (3.7%)
Saliva altered	1/27 (3.7%)
Small intestinal obstruction	1/27 (3.7%)
Stomatitis	16/27 (59.3%)
Vomiting	6/27 (22.2%)
General disorders
Asthenia	2/27 (7.4%)
Chest pain	1/27 (3.7%)
Chills	4/27 (14.8%)
Early satiety	1/27 (3.7%)
Fatigue	21/27 (77.8%)
Gait disturbance	1/27 (3.7%)
Mucosal inflammation	3/27 (11.1%)
Oedema peripheral	6/27 (22.2%)
Pain	3/27 (11.1%)
Pyrexia	7/27 (25.9%)
Immune system disorders
Seasonal allergy	1/27 (3.7%)
Infections and infestations
Bacteraemia	1/27 (3.7%)
Bronchitis	3/27 (11.1%)
Catheter related infection	1/27 (3.7%)
Herpes simplex	1/27 (3.7%)
Herpes zoster	1/27 (3.7%)
Laryngitis	1/27 (3.7%)
Oral candidiasis	2/27 (7.4%)
Sinusitis	2/27 (7.4%)
Tonsillitis	1/27 (3.7%)
Upper respiratory tract infection	1/27 (3.7%)
Urinary tract infection	2/27 (7.4%)
Viral rhinitis	1/27 (3.7%)
Injury, poisoning and procedural complications
Contusion	1/27 (3.7%)
Open wound	2/27 (7.4%)
Radius fracture	1/27 (3.7%)
Investigations
Aspartate aminotransferase increased	1/27 (3.7%)
Blood creatinine increased	3/27 (11.1%)
Blood urea increased	2/27 (7.4%)
Haemoglobin decreased	1/27 (3.7%)
International normalised ratio increased	1/27 (3.7%)
Neutrophil count	1/27 (3.7%)
Neutrophil count decreased	1/27 (3.7%)
Platelet count	2/27 (7.4%)
Urine output decreased	1/27 (3.7%)
Weight decreased	3/27 (11.1%)
White blood cell count	2/27 (7.4%)
Metabolism and nutrition disorders
Anorexia	4/27 (14.8%)
Decreased appetite	1/27 (3.7%)
Failure to thrive	1/27 (3.7%)
Fluid overload	1/27 (3.7%)
Fluid retention	1/27 (3.7%)
Hyperuricaemia	2/27 (7.4%)
Hypoalbuminaemia	2/27 (7.4%)
Hypoglycaemia	2/27 (7.4%)
Hypokalaemia	2/27 (7.4%)
Hypomagnesaemia	3/27 (11.1%)
Hyponatraemia	2/27 (7.4%)
Hypophosphataemia	1/27 (3.7%)
Type 2 diabetes mellitus	1/27 (3.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/27 (7.4%)
Back pain	2/27 (7.4%)
Groin pain	1/27 (3.7%)
Muscle spasms	1/27 (3.7%)
Muscular weakness	1/27 (3.7%)
Musculoskeletal chest pain	1/27 (3.7%)
Musculoskeletal pain	1/27 (3.7%)
Pain in extremity	4/27 (14.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	1/27 (3.7%)
Nervous system disorders
Aphonia	1/27 (3.7%)
Burning sensation	1/27 (3.7%)
Dizziness	2/27 (7.4%)
Dysgeusia	1/27 (3.7%)
Headache	2/27 (7.4%)
Lethargy	1/27 (3.7%)
Neuropathy peripheral	1/27 (3.7%)
Peripheral sensory neuropathy	1/27 (3.7%)
Sinus headache	1/27 (3.7%)
Somnolence	1/27 (3.7%)
Psychiatric disorders
Anxiety	1/27 (3.7%)
Confusional state	1/27 (3.7%)
Depression	1/27 (3.7%)
Insomina	2/27 (7.4%)
Renal and urinary disorders
Dysuria	2/27 (7.4%)
Haematuria	1/27 (3.7%)
Hydronephrosis	3/27 (11.1%)
Nephrolithiasis	1/27 (3.7%)
Oliguria	1/27 (3.7%)
Urinary incontinence	1/27 (3.7%)
Urinary retention	2/27 (7.4%)
Urinary tract pain	1/27 (3.7%)
Reproductive system and breast disorders
Vaginal discharge	1/27 (3.7%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/27 (3.7%)
Cough	5/27 (18.5%)
Dysphonia	4/27 (14.8%)
Dyspnoea	1/27 (3.7%)
Dyspnoea exertional	1/27 (3.7%)
Epistaxis	6/27 (22.2%)
Hiccups	1/27 (3.7%)
Hypoxia	1/27 (3.7%)
Lung infiltration	1/27 (3.7%)
Nasal discomfort	1/27 (3.7%)
Pharyngeal erythema	1/27 (3.7%)
Pharyngolaryngeal pain	6/27 (22.2%)
Pleural effusion	1/27 (3.7%)
Sneezing	1/27 (3.7%)
Throat irritation	1/27 (3.7%)
Skin and subcutaneous tissue disorders
Actinic keratosis	1/27 (3.7%)
Alopecia	1/27 (3.7%)
Decubitus ulcer	1/27 (3.7%)
Dry skin	1/27 (3.7%)
Ecchymosis	1/27 (3.7%)
Night sweats	2/27 (7.4%)
Petechiae	1/27 (3.7%)
Photodermatosis	1/27 (3.7%)
Pruritus	4/27 (14.8%)
Rash maculo-papular	2/27 (7.4%)
Skin disorder	1/27 (3.7%)
Skin exfoliation	1/27 (3.7%)
Urticaria	1/27 (3.7%)
Vascular disorders
Deep vein thrombosis	2/27 (7.4%)
Hypotension	2/27 (7.4%)
Orthostatic hypertension	1/27 (3.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.