Study of Pralatrexate & Gemcitabine With B12 & Folic Acid to Treat Relapsed/Refractory Lymphoproliferative Malignancies

• Sponsor: Acrotech Biopharma LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00481871
• Collaborator: (none)
• Enrollment: 119
• Locations: 15
• Arms: 2
• Duration (Months): 51
• Patients Per Site: 7.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study is for patients with lymphoproliferative malignancies that have progressed after receiving a previous treatment (relapsed) or are no longer responding to treatment (refractory). To be in this study, patients must have certain types of Hodgkin's lymphoma (HL), peripheral T-cell lymphoma (PTCL), or B-cell lymphoma, including Waldenstrom's macroglobulinemia.

This study is being done to find doses of the combination of pralatrexate and gemcitabine with vitamin B12 and folic acid that can be safely given to patients with these types of lymphoma and explore the effectiveness of the treatment.

Condition or Disease	Intervention/Treatment	Phase
Relapsed or Refractory Lymphoproliferative Malignancies; Hodgkin's Lymphoma; Peripheral T-cell Lymphoma; B-cell Lymphoma; Waldenstrom's Macroglobulinemia	Drug: Pralatrexate Injection; Drug: Gemcitabine Hydrochloride; Dietary Supplement: Vitamin B12; Dietary Supplement: Folic Acid	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 119 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2a Open-label Study of Pralatrexate and Gemcitabine With Vitamin B12 and Folic Acid Supplementation in Patients With Relapsed or Refractory Lymphoproliferative Malignancies
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pralatrexate & Gemcitabine - Sequential Days	Drug: Pralatrexate Injection; 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.; Other Names: FOLOTYN PDX Pralatrexate (RS)-10-propargyl-10-deazaaminopterin ; Drug: Gemcitabine Hydrochloride; Gemcitabine will be prepared and administered as an IV infusion as per manufacturer instructions. Sequential Dosing: 400 mg/m2 every 2 weeks (days 2 and 16) of a 4-week cycle until criteria for discontinuation per the protocol are met. Same Day Dosing: 600 mg/m2 every 2 weeks (days 1 and 15) of a 4-week cycle until criteria for discontinuation per the protocol are met.; Other Names: Gemcitabine Gemzar®, Eli Lilly and Company Gemcitabine Hydrochloride (HCl) for Injection ; Dietary Supplement: Vitamin B12; 1 mg intramuscular injection Administered within 10 weeks of enrollment, every 8-10 weeks throughout the study and for at least 30 days after last dose of pralatrexate.; Other Names: Cyanocobalamin ; Dietary Supplement: Folic Acid; 1 mg orally Administered daily for at least 7 days prior to start of pralatrexate, throughout the study and for at least 30 days after last dose of pralatrexate.; Other Names: Vitamin B9 Folate Folacin
Experimental: Pralatrexate & Gemcitabine - Same Day	Drug: Pralatrexate Injection; 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.; Other Names: FOLOTYN PDX Pralatrexate (RS)-10-propargyl-10-deazaaminopterin ; Drug: Gemcitabine Hydrochloride; Gemcitabine will be prepared and administered as an IV infusion as per manufacturer instructions. Sequential Dosing: 400 mg/m2 every 2 weeks (days 2 and 16) of a 4-week cycle until criteria for discontinuation per the protocol are met. Same Day Dosing: 600 mg/m2 every 2 weeks (days 1 and 15) of a 4-week cycle until criteria for discontinuation per the protocol are met.; Other Names: Gemcitabine Gemzar®, Eli Lilly and Company Gemcitabine Hydrochloride (HCl) for Injection ; Dietary Supplement: Vitamin B12; 1 mg intramuscular injection Administered within 10 weeks of enrollment, every 8-10 weeks throughout the study and for at least 30 days after last dose of pralatrexate.; Other Names: Cyanocobalamin ; Dietary Supplement: Folic Acid; 1 mg orally Administered daily for at least 7 days prior to start of pralatrexate, throughout the study and for at least 30 days after last dose of pralatrexate.; Other Names: Vitamin B9 Folate Folacin

Outcome Measures

Primary Outcome Measures

1. Objective Responses Assessed by International Workshop Criteria (IWC) [Assessed every 8 weeks (+/- 1 week) for Phase II and no less than every 3 cycles for Phase I]

   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.

Secondary Outcome Measures

1. Duration of Response [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]

   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)

2. Progression-free Survival (PFS) Time [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]

   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).

Eligibility Criteria

Criteria

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

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California at Los Angeles	Los Angeles	California	United States	90095-7077
2	Stanford University School of Medicine	Stanford	California	United States	94305
3	Rocky Mountain Cancer Center	Denver	Colorado	United States	80218
4	University of Chicago Hospital	Chicago	Illinois	United States	60637
5	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115-6013
6	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
7	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
8	The Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
9	New York University Hospital	New York	New York	United States	10016
10	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10017
11	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
12	Medical University of South Carolina	Charleston	South Carolina	United States	29425
13	UT MD Anderson Cancer Center	Houston	Texas	United States	77030
14	Cancer Therapy & Research Center	San Antonio	Texas	United States	78229-4427
15	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Acrotech Biopharma LLC

Investigators

• Study Director: Michael Saunders, MD, Spectrum Pharmaceuticals, Inc

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Acrotech Biopharma LLC
• ClinicalTrials.gov Identifier: NCT00481871
• Other Study ID Numbers: PDX-009
• First Posted: Jun 4, 2007
• Last Update Posted: Jan 7, 2020
• Last Verified: Dec 1, 2019

• Keywords provided by Acrotech Biopharma LLC: Lymphoproliferative malignancies; Lymphoma; Hodgkin's lymphoma (HL); Non-Hodgkin's lymphoma (NHL); PTCL; T/NK-cell leukemia/lymphoma; T-cell lymphoma/leukemia (HTLV 1+); Angioimmunoblastic T-cell lymphoma; Blastic NK lymphoma; Anaplastic large cell lymphoma; T/NK-cell lymphoma; Enteropathy-type intestinal lymphoma; Hepatosplenic T-cell lymphoma; Extranodal peripheral T/NK-cell lymphoma; Subcutaneous panniculitis T-cell lymphoma; Transformed mycosis fungoides; PDX; Pralatrexate; Gemcitabine; Gemzar; Vitamin B12; Folic acid
• Additional relevant MeSH terms: Lymphoma; Neoplasms; Hodgkin Disease; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Waldenstrom Macroglobulinemia; Vitamins; Folic Acid; Vitamin B 12; Hydroxocobalamin; Vitamin B Complex; Gemcitabine; 10-deazaaminopterin; Aminopterin

Study Results

Participant Flow

Recruitment Details	Patients were enrolled between May 2007 and July 2010 across 16 study sites, all in the United States.
Pre-assignment Detail	12 patients were enrolled but not treated. Of these, 9 patients had events after enrollment that rendered them ineligible; 2 patients had progressive disease (PD); 1 patient withdrew consent. Since they were never dosed, these 12 patients were not included in efficacy or safety assessments.

Arm/Group Title	Phase 1 Group A - Dose Finding	Phase 1 Group B - Dose Finding	Phase 1 Group C - Dose Finding	Phase 2 Group B	Phase 2 Group C
Arm/Group Description	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.	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.	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.	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.	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.
Period Title: Overall Study
STARTED	7	10	18	38	34
COMPLETED	7	10	17	38	34
NOT COMPLETED	0	0	1	0	0

Baseline Characteristics

Arm/Group Title	Phase 1 - Group A	Phase 1 - Group B	Phase 1 - Group C	Phase 2 - Group B	Phase 2 - Group C	Total
Arm/Group Description	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.	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.	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.	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.	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.	Total of all reporting groups
Overall Participants	7	10	18	38	34	107
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	2 28.6%	7 70%	10 55.6%	24 63.2%	28 82.4%	71 66.4%
>=65 years	5 71.4%	3 30%	8 44.4%	14 36.8%	6 17.6%	36 33.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.6 (15)	52.4 (18)	57.4 (17)	57.9 (16)	53.2 (15)	56.4 (16.1)
Sex: Female, Male (Count of Participants)
Female	4 57.1%	3 30%	4 22.2%	17 44.7%	14 41.2%	42 39.3%
Male	3 42.9%	7 70%	14 77.8%	21 55.3%	20 58.8%	65 60.7%
Region of Enrollment (participants) [Number]
United States	7 100%	10 100%	18 100%	38 100%	34 100%	107 100%

Outcome Measures

1. Primary Outcome

Title	Objective Responses Assessed by International Workshop Criteria (IWC)
Description	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.
Time Frame	Assessed every 8 weeks (+/- 1 week) for Phase II and no less than every 3 cycles for Phase I

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1	Phase 2 - Group B	Phase 2 - Group C
Arm/Group Description	Includes the Phase 1 dose-finding groups A, B, and C	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.	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.
Measure Participants	34	38	34
Number [participants]	8 114.3%	5 50%	7 38.9%

2. Secondary Outcome

Title	Duration of Response
Description	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)
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 1	Phase 2 - Group B	Phase 2 - Group C
Arm/Group Description	Includes the Phase 1 dose-finding groups A, B, and C	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.	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.
Measure Participants	8	5	7
Median (Full Range) [days]	174	210	170

3. Secondary Outcome

Title	Progression-free Survival (PFS) Time
Description	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).
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 1	Phase 2 - Group B	Phase 2 - Group C
Arm/Group Description	Includes the Phase 1 dose-finding groups A, B, and C	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.	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.
Measure Participants	34	38	34
Median (95% Confidence Interval) [days]	53.0	59.0	54.0

Adverse Events

Arm/Group Title	Phase 1		Phase 2 - Group B		Phase 2 - Group C
Arm/Group Description	Patients that received at least one dose of pralatrexate in the Phase 1 portion of the study		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.		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.
All Cause Mortality
	Phase 1		Phase 2 - Group B		Phase 2 - Group C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Phase 1		Phase 2 - Group B		Phase 2 - Group C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/35 (51.4%)		13/38 (34.2%)		16/34 (47.1%)
Blood and lymphatic system disorders
febrile neutropenia	2/35 (5.7%)		1/38 (2.6%)		0/34 (0%)
pancytopenia	1/35 (2.9%)		0/38 (0%)		0/34 (0%)
thrombocytopenia	1/35 (2.9%)		1/38 (2.6%)		1/34 (2.9%)
anaemia	0/35 (0%)		2/38 (5.3%)		0/34 (0%)
neutropenia	0/35 (0%)		0/38 (0%)		2/34 (5.9%)
Cardiac disorders
arrhythmia	1/35 (2.9%)		0/38 (0%)		0/34 (0%)
cardiac failure congestive	1/35 (2.9%)		1/38 (2.6%)		1/34 (2.9%)
myocardial infarction	2/35 (5.7%)		0/38 (0%)		0/34 (0%)
tachycardia	1/35 (2.9%)		1/38 (2.6%)		0/34 (0%)
atrial flutter	0/35 (0%)		0/38 (0%)		1/34 (2.9%)
bradycardia	0/35 (0%)		0/38 (0%)		1/34 (2.9%)
cardio-respiratory arrest	0/35 (0%)		1/38 (2.6%)		0/34 (0%)
ventricular arrhythmia	0/35 (0%)		1/38 (2.6%)		0/34 (0%)
Gastrointestinal disorders
diarrhoea	0/35 (0%)		0/38 (0%)		1/34 (2.9%)
oesophagitis	0/35 (0%)		1/38 (2.6%)		0/34 (0%)
stomatitis	0/35 (0%)		0/38 (0%)		2/34 (5.9%)
abdominal pain	0/35 (0%)		0/38 (0%)		1/34 (2.9%)
small intestinal obstruction	0/35 (0%)		0/38 (0%)		1/34 (2.9%)
General disorders
pyrexia	2/35 (5.7%)		4/38 (10.5%)		7/34 (20.6%)
chills	0/35 (0%)		1/38 (2.6%)		1/34 (2.9%)
fatigue	0/35 (0%)		1/38 (2.6%)		0/34 (0%)
multi-organ failure	0/35 (0%)		1/38 (2.6%)		0/34 (0%)
asthenia	0/35 (0%)		1/38 (2.6%)		0/34 (0%)
non-cardiac chest pain	0/35 (0%)		0/38 (0%)		1/34 (2.9%)
pain	0/35 (0%)		1/38 (2.6%)		0/34 (0%)
Infections and infestations
cellulitis	3/35 (8.6%)		1/38 (2.6%)		1/34 (2.9%)
pneumonia	3/35 (8.6%)		1/38 (2.6%)		2/34 (5.9%)
sepsis	0/35 (0%)		1/38 (2.6%)		0/34 (0%)
bacteraemia	0/35 (0%)		0/38 (0%)		1/34 (2.9%)
oral candidiasis	0/35 (0%)		0/38 (0%)		1/34 (2.9%)
respiratory syncytial virus infection	0/35 (0%)		0/38 (0%)		1/34 (2.9%)
sepsis syndrome	0/35 (0%)		1/38 (2.6%)		0/34 (0%)
urinary tract infection	0/35 (0%)		0/38 (0%)		1/34 (2.9%)
Injury, poisoning and procedural complications
femoral neck fracture	0/35 (0%)		1/38 (2.6%)		0/34 (0%)
accidental overdose	0/35 (0%)		0/38 (0%)		1/34 (2.9%)
Investigations
weight decreased	1/35 (2.9%)		0/38 (0%)		0/34 (0%)
Metabolism and nutrition disorders
dehydration	0/35 (0%)		0/38 (0%)		2/34 (5.9%)
electrolyte imbalance	0/35 (0%)		1/38 (2.6%)		0/34 (0%)
hyponatraemia	0/35 (0%)		1/38 (2.6%)		0/34 (0%)
hypovolaemia	0/35 (0%)		1/38 (2.6%)		0/34 (0%)
Musculoskeletal and connective tissue disorders
back pain	0/35 (0%)		0/38 (0%)		1/34 (2.9%)
muscular weakness	0/35 (0%)		1/38 (2.6%)		0/34 (0%)
musculoskeletal chest pain	0/35 (0%)		0/38 (0%)		1/34 (2.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
tumor lysis syndrome	0/35 (0%)		0/38 (0%)		1/34 (2.9%)
Nervous system disorders
altered state of consciousness	1/35 (2.9%)		0/38 (0%)		0/34 (0%)
cerebral haemorrhage	0/35 (0%)		1/38 (2.6%)		0/34 (0%)
Psychiatric disorders
delirium tremens	1/35 (2.9%)		0/38 (0%)		0/34 (0%)
mental status changes	1/35 (2.9%)		0/38 (0%)		0/34 (0%)
Renal and urinary disorders
renal failure acute	0/35 (0%)		2/38 (5.3%)		2/34 (5.9%)
hydronephrosis	0/35 (0%)		0/38 (0%)		2/34 (5.9%)
Respiratory, thoracic and mediastinal disorders
pleural effusion	1/35 (2.9%)		0/38 (0%)		0/34 (0%)
pneumonitis	2/35 (5.7%)		1/38 (2.6%)		0/34 (0%)
pulmonary embolism	1/35 (2.9%)		0/38 (0%)		0/34 (0%)
upper airway obstruction	1/35 (2.9%)		0/38 (0%)		0/34 (0%)
dyspnoea	0/35 (0%)		0/38 (0%)		4/34 (11.8%)
hypoxia	0/35 (0%)		0/38 (0%)		2/34 (5.9%)
pharyngolaryngeal pain	0/35 (0%)		0/38 (0%)		1/34 (2.9%)
pleurisy	0/35 (0%)		0/38 (0%)		1/34 (2.9%)
Skin and subcutaneous tissue disorders
rash maculo-papular	0/35 (0%)		1/38 (2.6%)		0/34 (0%)
skin exfoliation	0/35 (0%)		1/38 (2.6%)		0/34 (0%)
Surgical and medical procedures
pain management	0/35 (0%)		0/38 (0%)		1/34 (2.9%)
Vascular disorders
thrombophlebitis superficial	1/35 (2.9%)		0/38 (0%)		0/34 (0%)
hypotension	0/35 (0%)		2/38 (5.3%)		1/34 (2.9%)
lymphoedema	0/35 (0%)		1/38 (2.6%)		0/34 (0%)
Other (Not Including Serious) Adverse Events
	Phase 1		Phase 2 - Group B		Phase 2 - Group C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/35 (100%)		38/38 (100%)		34/34 (100%)
Blood and lymphatic system disorders
anaemia	19/35 (54.3%)		14/38 (36.8%)		9/34 (26.5%)
neutropenia	16/35 (45.7%)		14/38 (36.8%)		8/34 (23.5%)
thrombocytopenia	14/35 (40%)		16/38 (42.1%)		8/34 (23.5%)
leukopenia	5/35 (14.3%)		4/38 (10.5%)		3/34 (8.8%)
febrile neutropenia	3/35 (8.6%)		2/38 (5.3%)		1/34 (2.9%)
lymphopenia	2/35 (5.7%)		1/38 (2.6%)		0/34 (0%)
pancytopenia	2/35 (5.7%)		0/38 (0%)		0/34 (0%)
Cardiac disorders
palpitations	4/35 (11.4%)		0/38 (0%)		1/34 (2.9%)
tachycardia	3/35 (8.6%)		3/38 (7.9%)		2/34 (5.9%)
myocardial infarction	2/35 (5.7%)		0/38 (0%)		0/34 (0%)
sinus tachycardia	0/35 (0%)		1/38 (2.6%)		2/34 (5.9%)
bradycardia	1/35 (2.9%)		0/38 (0%)		2/34 (5.9%)
Ear and labyrinth disorders
ear pain	0/35 (0%)		3/38 (7.9%)		1/34 (2.9%)
Eye disorders
lacrimation increased	0/35 (0%)		1/38 (2.6%)		2/34 (5.9%)
vision blurred	1/35 (2.9%)		1/38 (2.6%)		3/34 (8.8%)
ocular hyperaemia	1/35 (2.9%)		0/38 (0%)		2/34 (5.9%)
Gastrointestinal disorders
stomatitis	16/35 (45.7%)		9/38 (23.7%)		12/34 (35.3%)
nausea	15/35 (42.9%)		24/38 (63.2%)		21/34 (61.8%)
diarrhoea	13/35 (37.1%)		11/38 (28.9%)		8/34 (23.5%)
vomiting	12/35 (34.3%)		10/38 (26.3%)		9/34 (26.5%)
constipation	10/35 (28.6%)		10/38 (26.3%)		12/34 (35.3%)
abdominal pain upper	3/35 (8.6%)		1/38 (2.6%)		4/34 (11.8%)
abdominal pain	2/35 (5.7%)		6/38 (15.8%)		6/34 (17.6%)
dysphagia	2/35 (5.7%)		2/38 (5.3%)		1/34 (2.9%)
epigastric discomfort	2/35 (5.7%)		0/38 (0%)		1/34 (2.9%)
gastrooesophageal reflux disease	2/35 (5.7%)		1/38 (2.6%)		1/34 (2.9%)
gingival pain	2/35 (5.7%)		0/38 (0%)		0/34 (0%)
glossodynia	2/35 (5.7%)		0/38 (0%)		0/34 (0%)
haematochezia	2/35 (5.7%)		0/38 (0%)		0/34 (0%)
oral pain	2/35 (5.7%)		3/38 (7.9%)		2/34 (5.9%)
abdominal discomfort	1/35 (2.9%)		0/38 (0%)		3/34 (8.8%)
lip pain	0/35 (0%)		2/38 (5.3%)		0/34 (0%)
General disorders
fatigue	25/35 (71.4%)		18/38 (47.4%)		15/34 (44.1%)
pyrexia	23/35 (65.7%)		18/38 (47.4%)		15/34 (44.1%)
chills	6/35 (17.1%)		12/38 (31.6%)		4/34 (11.8%)
oedema peripheral	5/35 (14.3%)		6/38 (15.8%)		6/34 (17.6%)
influenza like illness	3/35 (8.6%)		1/38 (2.6%)		0/34 (0%)
asthenia	2/35 (5.7%)		4/38 (10.5%)		3/34 (8.8%)
chest discomfort	2/35 (5.7%)		1/38 (2.6%)		1/34 (2.9%)
chest pain	2/35 (5.7%)		1/38 (2.6%)		1/34 (2.9%)
non-cardiac chest pain	2/35 (5.7%)		0/38 (0%)		3/34 (8.8%)
pain	1/35 (2.9%)		2/38 (5.3%)		4/34 (11.8%)
catheter site pain	0/35 (0%)		2/38 (5.3%)		0/34 (0%)
pitting oedema	0/35 (0%)		2/38 (5.3%)		0/34 (0%)
Infections and infestations
cellulitis	4/35 (11.4%)		1/38 (2.6%)		0/34 (0%)
pneumonia	4/35 (11.4%)		2/38 (5.3%)		3/34 (8.8%)
oral candidiasis	2/35 (5.7%)		2/38 (5.3%)		2/34 (5.9%)
upper respiratory tract infection	2/35 (5.7%)		3/38 (7.9%)		3/34 (8.8%)
sepsis syndrome	0/35 (0%)		2/38 (5.3%)		0/34 (0%)
urinary tract infection	3/35 (8.6%)		1/38 (2.6%)		2/34 (5.9%)
Investigations
alanine aminotransferase increased	4/35 (11.4%)		3/38 (7.9%)		4/34 (11.8%)
alanine aminotransferase	2/35 (5.7%)		0/38 (0%)		0/34 (0%)
aspartate aminotransferase increased	2/35 (5.7%)		3/38 (7.9%)		2/34 (5.9%)
blood creatinine increased	2/35 (5.7%)		2/38 (5.3%)		2/34 (5.9%)
cardiac murmur	2/35 (5.7%)		0/38 (0%)		0/34 (0%)
platelet count decreased	2/35 (5.7%)		1/38 (2.6%)		2/34 (5.9%)
weight decreased	2/35 (5.7%)		0/38 (0%)		1/34 (2.9%)
white blood cell count	2/35 (5.7%)		0/38 (0%)		0/34 (0%)
neutrophil count decreased	1/35 (2.9%)		6/38 (15.8%)		2/34 (5.9%)
weight increased	0/35 (0%)		2/38 (5.3%)		1/34 (2.9%)
white blood cell count decreased	1/35 (2.9%)		3/38 (7.9%)		1/34 (2.9%)
blood lactate dehydrogenase increased	0/35 (0%)		2/38 (5.3%)		0/34 (0%)
haemoglobin decreased	1/35 (2.9%)		5/38 (13.2%)		0/34 (0%)
Metabolism and nutrition disorders
decreased appetite	5/35 (14.3%)		3/38 (7.9%)		1/34 (2.9%)
anorexia	3/35 (8.6%)		7/38 (18.4%)		5/34 (14.7%)
hyperuricaemia	2/35 (5.7%)		0/38 (0%)		0/34 (0%)
dehydration	1/35 (2.9%)		1/38 (2.6%)		3/34 (8.8%)
hypocalcaemia	0/35 (0%)		2/38 (5.3%)		0/34 (0%)
hypokalaemia	1/35 (2.9%)		1/38 (2.6%)		5/34 (14.7%)
hypomagnesaemia	0/35 (0%)		2/38 (5.3%)		3/34 (8.8%)
hyperglycaemia	0/35 (0%)		1/38 (2.6%)		2/34 (5.9%)
hypoglycaemia	0/35 (0%)		0/38 (0%)		2/34 (5.9%)
hyponatraemia	1/35 (2.9%)		4/38 (10.5%)		0/34 (0%)
Musculoskeletal and connective tissue disorders
back pain	5/35 (14.3%)		4/38 (10.5%)		3/34 (8.8%)
muscular weakness	4/35 (11.4%)		2/38 (5.3%)		0/34 (0%)
neck pain	3/35 (8.6%)		4/38 (10.5%)		2/34 (5.9%)
myalgia	2/35 (5.7%)		1/38 (2.6%)		4/34 (11.8%)
arthralgia	1/35 (2.9%)		3/38 (7.9%)		2/34 (5.9%)
bone pain	1/35 (2.9%)		0/38 (0%)		2/34 (5.9%)
muscle spasms	1/35 (2.9%)		3/38 (7.9%)		0/34 (0%)
pain in extremity	1/35 (2.9%)		4/38 (10.5%)		6/34 (17.6%)
musculoskeletal pain	3/35 (8.6%)		1/38 (2.6%)		3/34 (8.8%)
groin pain	0/35 (0%)		2/38 (5.3%)		0/34 (0%)
musculoskeletal chest pain	1/35 (2.9%)		0/38 (0%)		2/34 (5.9%)
Nervous system disorders
dizziness	8/35 (22.9%)		5/38 (13.2%)		8/34 (23.5%)
paraesthesia	8/35 (22.9%)		0/38 (0%)		1/34 (2.9%)
headache	7/35 (20%)		9/38 (23.7%)		6/34 (17.6%)
neuropathy peripheral	4/35 (11.4%)		3/38 (7.9%)		2/34 (5.9%)
hypoaesthesia	2/35 (5.7%)		2/38 (5.3%)		2/34 (5.9%)
memory impairment	0/35 (0%)		1/38 (2.6%)		2/34 (5.9%)
dysgeusia	0/35 (0%)		2/38 (5.3%)		1/34 (2.9%)
Psychiatric disorders
anxiety	3/35 (8.6%)		3/38 (7.9%)		1/34 (2.9%)
insomnia	1/35 (2.9%)		1/38 (2.6%)		3/34 (8.8%)
confusional state	0/35 (0%)		1/38 (2.6%)		2/34 (5.9%)
Renal and urinary disorders
renal failure acute	0/35 (0%)		2/38 (5.3%)		3/34 (8.8%)
hydronephrosis	1/35 (2.9%)		0/38 (0%)		2/34 (5.9%)
incontinence	0/35 (0%)		2/38 (5.3%)		0/34 (0%)
Respiratory, thoracic and mediastinal disorders
dyspnoea	7/35 (20%)		5/38 (13.2%)		9/34 (26.5%)
epistaxis	7/35 (20%)		2/38 (5.3%)		2/34 (5.9%)
cough	6/35 (17.1%)		8/38 (21.1%)		2/34 (5.9%)
wheezing	5/35 (14.3%)		0/38 (0%)		1/34 (2.9%)
hypoxia	4/35 (11.4%)		2/38 (5.3%)		4/34 (11.8%)
pharyngolaryngeal pain	4/35 (11.4%)		6/38 (15.8%)		4/34 (11.8%)
pleural effusion	4/35 (11.4%)		2/38 (5.3%)		1/34 (2.9%)
dysphonia	3/35 (8.6%)		2/38 (5.3%)		0/34 (0%)
productive cough	3/35 (8.6%)		2/38 (5.3%)		0/34 (0%)
pleuritic pain	2/35 (5.7%)		1/38 (2.6%)		1/34 (2.9%)
pneumonitis	2/35 (5.7%)		1/38 (2.6%)		0/34 (0%)
rhinitis allergic	2/35 (5.7%)		0/38 (0%)		0/34 (0%)
dyspnoea exertional	1/35 (2.9%)		3/38 (7.9%)		0/34 (0%)
nasal congestion	0/35 (0%)		1/38 (2.6%)		2/34 (5.9%)
haemoptysis	1/35 (2.9%)		3/38 (7.9%)		1/34 (2.9%)
rales	0/35 (0%)		2/38 (5.3%)		1/34 (2.9%)
Skin and subcutaneous tissue disorders
rash	5/35 (14.3%)		2/38 (5.3%)		2/34 (5.9%)
alopecia	4/35 (11.4%)		2/38 (5.3%)		0/34 (0%)
pruritus	4/35 (11.4%)		5/38 (13.2%)		5/34 (14.7%)
erythema	3/35 (8.6%)		2/38 (5.3%)		2/34 (5.9%)
night sweats	3/35 (8.6%)		5/38 (13.2%)		2/34 (5.9%)
swelling face	2/35 (5.7%)		0/38 (0%)		0/34 (0%)
rash pruritic	0/35 (0%)		7/38 (18.4%)		1/34 (2.9%)
rash erythematous	0/35 (0%)		2/38 (5.3%)		0/34 (0%)
rash maculo-papular	0/35 (0%)		2/38 (5.3%)		0/34 (0%)
skin lesion	1/35 (2.9%)		1/38 (2.6%)		2/34 (5.9%)
urticaria	1/35 (2.9%)		0/38 (0%)		2/34 (5.9%)
Vascular disorders
hypotension	6/35 (17.1%)		3/38 (7.9%)		3/34 (8.8%)
flushing	2/35 (5.7%)		1/38 (2.6%)		2/34 (5.9%)
hypertension	2/35 (5.7%)		1/38 (2.6%)		1/34 (2.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.