BBR 2778 for Relapsed, Aggressive Non-Hodgkin's Lymphoma (NHL)

• Sponsor: CTI BioPharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00088530
• Collaborator: (none)
• Enrollment: 140
• Locations: 99
• Arms: 2
• Duration (Months): 72
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

BBR 2778 is a novel aza-anthracenedione that has activity in experimental tumors and shows reduced potential for cardiotoxicity in animal models. This cytotoxic agent has structural similarities with mitoxantrone as well as general similarities with anthracyclines (such as the tricyclic central quinoid chromophore).

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Non-Hodgkin	Drug: pixantrone, cyclophosphamide, vincristine, rituximab, prednisone; Drug: Vinorelbine, Oxalplatin, Ifosfasmide, Etoposide, Mitoxatrone, Gemcitabine or Rituximab	Phase 3

Detailed Description

The primary study objective is to compare the efficacy of BBR 2778 to a selection of single agents. Secondary objectives are to compare the safety and tolerability of BBR 2778 to a selection of single agents, and to assess the pharmacokinetic parameters of BBR 2778 in a subset of this patient population.

Study Design

• Study Type: Interventional
• Actual Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pixantrone (BBR 2778) Versus Other Chemotherapeutic Agents for Third-line Single Agent Treatment of Patients With Relapsed Aggressive Non-Hodgkin's Lymphoma: A Randomized, Controlled, Phase III Comparative Trial
• Study Start Date: Jul 1, 2004
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental Arm Pixantrone (BBR2778)	Drug: pixantrone, cyclophosphamide, vincristine, rituximab, prednisone; Day 1: pixantrone (150 mg/m2), cyclophosphamide (750 mg/m2), vincristine (1.4 mg/m2), rituximab (375 mg/m2) Days 1-5: prednisone (100 mg/day); Other Names: BBR2778
Active Comparator: Comparator Arm To be chosen by the investigator, among vinorelbine, oxaliplatin, ifosfamide, etoposide or mitoxantrone	Drug: Vinorelbine, Oxalplatin, Ifosfasmide, Etoposide, Mitoxatrone, Gemcitabine or Rituximab; Day 1: cyclophosphamide (750 mg/m2), vincristine (1.4 mg/m2), rituximab (375 mg/m2) Days 1-5: prednisone (100 mg/day)

Outcome Measures

Primary Outcome Measures

1. Complete Response (CR) and Complete Response Unconfirmed (CRu) [EOT; approximately 6 months]

   Proportion of patients with a best response of complete response (CR) or Complete Response unconfirmed (CRu) in the End Of Treatment (EOT) or End Of Study (EOS) analyses by independent assessment in the Intent-to-treat (ITT) population through the End of Treatment (EOT)

Secondary Outcome Measures

1. Progression-Free Survival (PFS) [18 months after 6 cycles of treatment; approximately 24 months]

   The time between the date of randomization and the date of the initial documentation of progressive/relapsed disease or death due to any cause.

2. Overall Survival [18 months after 6 cycles of treatment; approximately 24 months]

   The time between the date of randomization and the date of death due to any cause.

3. Overall Response Rate (ORR) Lasting at Least 4 Months [approximately 24 months]

   The proportion of patients with Complete response or Partial Response with a difference from the first documented objective response to disease progression or death of at least 4 months.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed aggressive [de novo or transformed] NHL according to REAL/WHO classification.

• At least one objectively measurable lesion as demonstrated by CT, spiral CT, or MRI and plain radiograph of the chest (chest x-ray, for chest lesions only) that can be followed for response as target lesion.

• Relapse after 2 or more prior regimens of chemotherapy

• ECOG performance status of 0, 1, or 2

• Adequate hematologic, renal and hepatic function

• LVEF ≥50% determined by MUGA scan

Exclusion Criteria:

• Prior treatment with a cumulative dose of doxorubicin or equivalent exceeding 450 mg/m²

• Prior allogenic stem cell transplant

• Histological diagnosis of Burkitt lymphoma, lymphoblastic lymphoma or Mantle cell lymphoma

• Active CNS lymphoma or HIV-related lymphoma.

• Any chemotherapy, radiotherapy, or other anticancer treatment (including corticosteroid, 10 or more mg/day of prednisone or equivalent) within the 2 weeks before randomization

• Pregnant women or nursing mothers

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Robert A. Moss, M.D., FACP, Inc.	Fountain Valley	California	United States	92708
2	UCLA Medical Center	Los Angeles	California	United States	90095
3	Watson Clinic for Cancer Care and Research	Lakeland	Florida	United States	33805
4	Rush University Medical Center	Chicago	Illinois	United States	60612
5	New Mexico Oncology/Hematology	Albuquerque	New Mexico	United States	87109
6	SUNY Upstate Medical University	Syracuse	New York	United States	13210
7	Duke University Medical Center	Durham	North Carolina	United States	27710
8	Northwest Kaiser Permanente	Portland	Oregon	United States	97227
9	Northern Utah Hematology Oncology, P.C.	Ogden	Utah	United States	84403
10	Clinica Modelo S.A.	Parana	Entre Rios	Argentina	3100
11	Instituto de Investigaciones Clinicas	Rosario	Santa Fe	Argentina	2000
12	Centro Oncologico Rosario	Rosario	Santa Fe	Argentina	S2000DSK
13	FUNDALEU - fundacion para combatir le Leucernia	Buenos Aires		Argentina	1114
14	Hospital Universitario Austral	Buenos Aires		Argentina	B1629AHJ
15	Academia Nacional de Medicina	Caba		Argentina	C1425AUM
16	Hospital Privado Centro Medico de Cordoba S.A.	Cordoba		Argentina	X5016KEH
17	ISIS Clinica Especializada	Santa Fe		Argentina	S3000FFU
18	University Gernal Hospital for Active Treatment "Alexandrovska" - Clinic of Hematology	Sofia		Bulgaria	1431
19	National Centre for Hemotransfusion	Sofia		Bulgaria	1756
20	University General Hospital for Active Treatment "St. Marina" Clinic of Hematology	Varna		Bulgaria	9000
21	Hospital CIMA San Jose	Escazu		Costa Rica
22	Hospital Oncologico de Solca	Capilla Mauta	Guayaquil	Ecuador	3623
23	Hospital Carlos Andrade Marin Oncologia	Quito,	Pinchincha	Ecuador	17
24	Hospital Solca Quito	Quito		Ecuador
25	Tartu University Clinics, Hematology Oncology Clinic	Tartu		Estonia	51014
26	Institute Bergonie	Bordeaux		France	33076
27	Centre Hospitalier Lyo Sud, Service d'Hematologie et d'Oncologie	Pierre-Benite		France	69310
28	Hopitaux Universitaires de Strabourg - Hopital de Hautepierre	Strasbourg		France	67200
29	Staedtische Kliniken Hoechst	Frankfurt	HE	Germany	65929
30	Charite, Campus Benjamin Franklin	Berlin		Germany	12200
31	Universitatklinik des Saarlandes, Innere Medzin I	Hamburg		Germany	66421
32	Westpfalzklinikum Kaiserslautern	Kaiserslautern		Germany	67653
33	Klinikum der Universitaet zu Koeln	Koeln		Germany	50924
34	Kliniken Maria Hilf GmbH	Moenchengladbach		Germany	41063
35	Mutterhaus der Borromaeerinne	Trier		Germany	54290
36	Szent Laszlo Korhaz	Budapest		Hungary	H-1097
37	Petz Aladar Megyei Okato Korhaz	Gyor		Hungary	H-9024
38	Bekes Megyei Pandy Kalman Korhaz	Gyula		Hungary	5701
39	Kaposi Mor Megyei Korhaz	Kaposvar		Hungary	H-7400
40	Pecsi Tudomanyegyetem	Pecs		Hungary	H-7624
41	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Orvos-es Gyogy II	Szeged		Hungary	6701
42	Indo-American Cancer Institute & Research Center	Hyderabaad	AndhPrad	India	500034
43	Nizam's Institute of Medical Sciences	Panjagutta	Hyderabad	India	500082
44	Manipal Hospital	Bangalore	Karnataka	India	560017
45	Shirdi Sai Baba Cancer Hospital, K.M.C. Manipal	Manipala	Karna	India	576119
46	Regional Cancer Center	Thiruvananthapuram	Kerla	India	695011
47	Bhagwan Mahaveer Cancer Hospital & Research Center	Jaipur	Rajasthan	India	302017
48	M.S. Ramaiah Medical College	Bangalore		India	560 054
49	Tata Memorial Hospital	Mumbai		India	400012
50	Policlinico S. Orsola, Instituto di Ematologia	Bologna		Italy	40138
51	Ospedale Oncologico "A. Businco"	Cagliari		Italy	09100
52	Ospedale S. Martino	Genova		Italy	16132
53	Universita degli Studi Perugia Policlinico Monteluce	Perugia		Italy	06122
54	Azienda ospedaliera Pisana "Santa Chiara"	Pisa		Italy	56126
55	Azienda Ospedaliera Pisanan "Santana Chiara"	Pisa		Italy	56126
56	Ospedale Oncolgoico Regionale della Basilicata	Rionero in Vulture		Italy	85028
57	Ospedale S. Eugenio	Roma		Italy	00144
58	Universita La Sapienza	Roma		Italy	00161
59	Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo		Italy
60	Policlinico S. Maria alle Scotte	Siena		Italy	53100
61	Presidio San Giuseppe Moscati	Taranto		Italy	74100
62	Ospedale Civile	Udine		Italy	33100
63	Fundacion Centro De Investigacion	Medellin	Columbia	Mexico
64	Medical Solutions	Guatimala	Guatemala	Mexico
65	Complejo Hospitalario "Arnulfo Arias Madrid	Panama		Panama
66	Hospital Edgardo Rebagliati Martins	Lima		Peru	11
67	Onococenter	San Borja		Peru
68	Klinika Hematologii, Onkologii i Chorob Wewnetrznych	Gdansk		Poland	80-211
69	Brasov Counthy Hospital	Brasov		Romania	500326
70	Colentina Clinical Hospital Hem Dept	Bucharest		Romania	020125
71	Fundei Clinical Institute	Bucharest		Romania	022328
72	Prof. Dr. Ian Chiricuta, Institute of Oncology, Radiotheraphy	Cluj Napoca		Romania	400015
73	Institutul Oncologic "Ion Chiricuta" Oncologie Medicala	Cluj-Napoca		Romania	400015
74	Mures County Clinical Hospital	Targu Mures		Romania	540136
75	State Medical Institution Altai Territorial Oncological Center	Barnaul		Russian Federation	656049
76	State Medical Institution Replubican Oncological Center	Bashkortostan		Russian Federation	450054
77	State Therapeutical & Prophlatic Institution: Cheylabinsk Regional Oncological Center	Chelyabinsk		Russian Federation	454087
78	State Medical Institution	Irkutsk		Russian Federation	664035
79	State Medical Institution: Clinical Oncological Center	Krasnodar		Russian Federation	350040
80	Russian Oncological Research Center n.a. N.N. Blokhin	Moscow		Russian Federation	115478
81	State Institution: Hematological Research Center under the Russian Academy of Medical Sciences	Moscow		Russian Federation	125167
82	State Institution: Moscow Regional Research Clinical institute n.a. M.F.	Moscow		Russian Federation	129110
83	Semashko Central Clinical Hospital	Moscow		Russian Federation	129128
84	Medical Radiological Research Center under the Russian academey of Medical Sciences	Obninsk		Russian Federation	249036
85	Research Insitute of Hematology and Blood Transfusion	St. Petersburg		Russian Federation	191024
86	St. Petersburg Pavlov State Medical Clinic of Intensive Care & Bone Marrow Transplantation	St. Petersburg		Russian Federation	197022
87	St. Petersburg State Medical univ. n.a. I.P. Pavlov	St. Petersburg		Russian Federation	197022
88	St. Petersburg State Medical Institution: Municipal Hospital #31	St. Petersburg		Russian Federation	197110
89	Central Research Rontgenological and Radiological Institute	St. Petersburg		Russian Federation	197758
90	State Research Institution: Research Institute of Oncology	St. Petersburg		Russian Federation	197758
91	Institute of Clinical Radiology of the Research Center for Radiation Medicine under the UAMS	Kyiv		Ukraine	03115
92	Kyiv Bone Marrow Transplantation	Kyiv		Ukraine	03115
93	Institute of Blood Pathology & Transfusion Medicine under the UAMS	Lviv		Ukraine	79044
94	Zhtomyr O.F. Gerbachevsky Regional Hospital	Zhytomyr		Ukraine	10002
95	Beatson Oncology Centre, Western Infirmary	Glasgow		United Kingdom	G11 6T
96	St. Georges Hospital	London		United Kingdom	SW17 0QT
97	Weston Park Hospital	Sheffield		United Kingdom	S10 2Sj
98	Hospital Maciel	Montevideo		Uruguay	11000
99	Hospital Policial de Montevideo	Poblado Montevideo Chico		Uruguay	12000

Sponsors and Collaborators

• CTI BioPharma

Investigators

• Study Director: Simran Singh, Sr. Director, Clinical Operations

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: CTI BioPharma
• ClinicalTrials.gov Identifier: NCT00088530
• Other Study ID Numbers: PIX301; NCT00101049
• First Posted: Jul 29, 2004
• Last Update Posted: Feb 5, 2020
• Last Verified: Jan 1, 2020

• Keywords provided by CTI BioPharma: Pixantrone; Non-Hodgkins lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Gemcitabine; Prednisone; Cyclophosphamide; Rituximab; Etoposide; Vincristine; Vinorelbine; Pixantrone

Study Results

Participant Flow

Recruitment Details	Patients were enrolled from 66 sites: 6 in the U.S, 4 in France, 3 in Bulgaria, 4 sites in Hungary, 3 in Ukraine, 11 in Italy, 2 in Romania, 3 in United Kingdom, 2 in Poland, 2 in Germany, 3 in Peru, 6 in Argentina, 1 in Colombia, 2 in Ecuador, 1 in Uruguay, 5 in Russia and 8 in India.

Arm/Group Title	Experimental Group	Comparator Group
Arm/Group Description	Pixantrone (BBR 2778) 85 mg/m2 on days 1, 8 and 15 of each 28-day cycle)	Vinorelbine or Oxalplatin or Ifosfasmide or Etoposide or Mitoxatrone or Gemcitabine or Rituximab
Period Title: Overall Study
STARTED	70	70
COMPLETED	20	16
NOT COMPLETED	50	54

Baseline Characteristics

Arm/Group Title	Experimental Group	Comparator Group	Total
Arm/Group Description	Pixantrone (BBR 2778) 85 mg/m2 on days 1, 8 and 15 of each 28-day cycle	Vinorelbine or Oxalplatin or Ifosfasmide or Etoposide or Mitoxatrone or Gemcitabine or Rituximab	Total of all reporting groups
Overall Participants	70	70	140
Age (years) [Mean (Standard Deviation) ]
Age at Randomization (years)	58.2 (13.5)	56.2 (12.9)	57.2 (13.2)
Age, Customized (Count of Participants)
18 to < 30	5 7.1%	2 2.9%	7 5%
30 to < 40	2 2.9%	9 12.9%	11 7.9%
40 to < 50	9 12.9%	7 10%	16 11.4%
50 to < 60	18 25.7%	21 30%	39 27.9%
60 to < 70	20 28.6%	21 30%	41 29.3%
70 to < 80	15 21.4%	9 12.9%	24 17.1%
≥ 80	1 1.4%	1 1.4%	2 1.4%
Sex: Female, Male (Count of Participants)
Female	24 34.3%	30 42.9%	54 38.6%
Male	46 65.7%	40 57.1%	86 61.4%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	46 65.7%	44 62.9%	90 64.3%
Black	0 0%	0 0%	0 0%
Asian	10 14.3%	13 18.6%	23 16.4%
Hispanic	7 10%	6 8.6%	13 9.3%
Native American	1 1.4%	1 1.4%	2 1.4%
Other	6 8.6%	6 8.6%	12 8.6%
Region of Enrollment (participants) [Number]
North America	4 5.7%	4 5.7%	8 5.7%
Argentina	6 8.6%	5 7.1%	11 7.9%
Bulgaria	6 8.6%	3 4.3%	9 6.4%
Colombia	1 1.4%	0 0%	1 0.7%
Ecuador	3 4.3%	4 5.7%	7 5%
Hungary	5 7.1%	5 7.1%	10 7.1%
India	9 12.9%	12 17.1%	21 15%
Peru	9 12.9%	8 11.4%	17 12.1%
Poland	2 2.9%	0 0%	2 1.4%
Romania	1 1.4%	1 1.4%	2 1.4%
Russian Federation	4 5.7%	5 7.1%	9 6.4%
Ukraine	1 1.4%	3 4.3%	4 2.9%
Uruguay	0 0%	1 1.4%	1 0.7%
France	4 5.7%	4 5.7%	8 5.7%
United Kingdom	4 5.7%	3 4.3%	7 5%
Germany	3 4.3%	0 0%	3 2.1%
Italy	8 11.4%	12 17.1%	20 14.3%
Baseline ECOG Performance Status (Count of Participants)
0	26 37.1%	23 32.9%	49 35%
1	30 42.9%	32 45.7%	62 44.3%
2	14 20%	14 20%	28 20%
3	0 0%	1 1.4%	1 0.7%

Outcome Measures

1. Primary Outcome

Title	Complete Response (CR) and Complete Response Unconfirmed (CRu)
Description	Proportion of patients with a best response of complete response (CR) or Complete Response unconfirmed (CRu) in the End Of Treatment (EOT) or End Of Study (EOS) analyses by independent assessment in the Intent-to-treat (ITT) population through the End of Treatment (EOT)
Time Frame	EOT; approximately 6 months

Outcome Measure Data

Analysis Population Description

Intent to Treat (all randomized patients)

Arm/Group Title	Experimental Group	Comparator Group
Arm/Group Description	Pixantrone (BBR 2778) 85 mg/m2 on days 1, 8 and 15 of each 28-day cycle	Vinorelbine or Oxalplatin or Ifosfasmide or Etoposide or Mitoxatrone or Gemcitabine or Rituximab
Measure Participants	70	70
END OF TREATMENT: CR/CRu, n (%)	20.0	5.7
END OF STUDY: CR/CRu, n (%)	24.3	7.1

2. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	The time between the date of randomization and the date of the initial documentation of progressive/relapsed disease or death due to any cause.
Time Frame	18 months after 6 cycles of treatment; approximately 24 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat patients

Arm/Group Title	Experimental Group	Comparator Group
Arm/Group Description	Pixantrone (BBR 2778) 85 mg/m2 on days 1, 8 and 15 of each 28-day cycle	Vinorelbine or Oxalplatin or Ifosfasmide or Etoposide or Mitoxatrone or Gemcitabine or Rituximab
Measure Participants	70	70
Median (95% Confidence Interval) [months]	5.3	2.6

3. Secondary Outcome

Title	Overall Survival
Description	The time between the date of randomization and the date of death due to any cause.
Time Frame	18 months after 6 cycles of treatment; approximately 24 months

Outcome Measure Data

Analysis Population Description

Intent-To-Treat (ITT) Population.

Arm/Group Title	Experimental Group	Comparator Group
Arm/Group Description	Pixantrone (BBR 2778) 85 mg/m2 on days 1, 8 and 15 of each 28-day cycle	Vinorelbine or Oxalplatin or Ifosfasmide or Etoposide or Mitoxatrone or Gemcitabine or Rituximab
Measure Participants	70	70
Median (95% Confidence Interval) [Months]	10.2	7.6

4. Secondary Outcome

Title	Overall Response Rate (ORR) Lasting at Least 4 Months
Description	The proportion of patients with Complete response or Partial Response with a difference from the first documented objective response to disease progression or death of at least 4 months.
Time Frame	approximately 24 months

Outcome Measure Data

Analysis Population Description

Intent-To-Treat (ITT) population

Arm/Group Title	Experimental Group	Comparator Group
Arm/Group Description	Pixantrone (BBR 2778) 85 mg/m2 on days 1, 8 and 15 of each 28-day cycle	Vinorelbine or Oxalplatin or Ifosfasmide or Etoposide or Mitoxatrone or Gemcitabine or Rituximab
Measure Participants	70	70
Number [participants]	12 17.1%	6 8.6%

Adverse Events

Time Frame	2 year, 3 months. Adverse event tables presented include data reported through End Of Study
Adverse Event Reporting Description	An adverse event was defined as any noxious and unintended sign, symptom, or disease that began or worsened from the time the patient signed the Informed Consent Form to participate in the study until 30 days after last study treatment, regardless of whether event was considered related or unrelated to study drug. Treatment emergent adverse events were summarized in the table below (patients who received study drug - 68/67). NCI CTCAE V3 was used to assess toxicities observed during the study.
Arm/Group Title	Experimental Group		Comparator Group
Arm/Group Description	Pixantrone (BBR 2778) 85 mg/m2 on days 1, 8 and 15 of each 28-day cycle		Vinorelbine or Oxalplatin or Ifosfasmide or Etoposide or Mitoxatrone or Gemcitabine or Rituximab
All Cause Mortality
	Experimental Group		Comparator Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/68 (72.1%)		52/67 (77.6%)
Serious Adverse Events
	Experimental Group		Comparator Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/68 (51.5%)		30/67 (44.8%)
Blood and lymphatic system disorders
Neutropenia	9/68 (13.2%)		6/67 (9%)
Thrombocytopenia	1/68 (1.5%)		6/67 (9%)
Anemia	2/68 (2.9%)		5/67 (7.5%)
Febrile neutropenia	4/68 (5.9%)		2/67 (3%)
Leukopenia	4/68 (5.9%)		2/67 (3%)
Lymphadenopathy	0/68 (0%)		1/67 (1.5%)
Pancytopenia	0/68 (0%)		1/67 (1.5%)
Cardiac disorders
Cardiac Failure	2/68 (2.9%)		1/67 (1.5%)
Cardiac Failure Congestive	2/68 (2.9%)		0/67 (0%)
Cardiac Arrest	1/68 (1.5%)		0/67 (0%)
Cyanosis	1/68 (1.5%)		0/67 (0%)
Myocardial Ischaemia	1/68 (1.5%)		0/67 (0%)
Myocarditis	0/68 (0%)		1/67 (1.5%)
Pericardial Effusion	1/68 (1.5%)		0/67 (0%)
Sinus Tachycardia	0/68 (0%)		1/67 (1.5%)
Tachycardia	1/68 (1.5%)		0/67 (0%)
Ventricular Extrasystoles	0/68 (0%)		1/67 (1.5%)
Eye disorders
Keratitis	1/68 (1.5%)		0/67 (0%)
Gastrointestinal disorders
Abdominal Pain	3/68 (4.4%)		3/67 (4.5%)
Vomiting	0/68 (0%)		2/67 (3%)
Abdominal Distension	0/68 (0%)		1/67 (1.5%)
Diarrhoea	0/68 (0%)		1/67 (1.5%)
Dysphagia	0/68 (0%)		1/67 (1.5%)
Ileus	1/68 (1.5%)		0/67 (0%)
Nausea	0/68 (0%)		1/67 (1.5%)
General disorders
Pyrexia	7/68 (10.3%)		7/67 (10.4%)
Asthenia	1/68 (1.5%)		1/67 (1.5%)
Oedema Peripheral	1/68 (1.5%)		1/67 (1.5%)
Fatigue	0/68 (0%)		1/67 (1.5%)
Generalised Oedema	0/68 (0%)		1/67 (1.5%)
Mucosal Inflammation	0/68 (0%)		1/67 (1.5%)
Multi-organ Failure	1/68 (1.5%)		0/67 (0%)
Non-cardiac Chest pain	1/68 (1.5%)		0/67 (0%)
Performance Status Decreased	0/68 (0%)		1/67 (1.5%)
Hepatobiliary disorders
Cholestasis	1/68 (1.5%)		0/67 (0%)
Jaundice	1/68 (1.5%)		0/67 (0%)
Infections and infestations
Pneumonia	5/68 (7.4%)		4/67 (6%)
Cellulitis	2/68 (2.9%)		2/67 (3%)
Bronchitis	2/68 (2.9%)		0/67 (0%)
Sepsis	1/68 (1.5%)		1/67 (1.5%)
Septic Shock	2/68 (2.9%)		0/67 (0%)
Candiddiasis	1/68 (1.5%)		0/67 (0%)
Catheter realted infection	1/68 (1.5%)		0/67 (0%)
Escherichia Urinary Tract Infection	0/68 (0%)		1/67 (1.5%)
Gastroenteristic Salmonella	1/68 (1.5%)		0/67 (0%)
Gastrointestinal Infection	0/68 (0%)		1/67 (1.5%)
Herpes Virus Infection	1/68 (1.5%)		0/67 (0%)
Neutropenic Sepsis	0/68 (0%)		1/67 (1.5%)
Pharyngitis	0/68 (0%)		1/67 (1.5%)
Postoperative Wound Infection	0/68 (0%)		1/67 (1.5%)
Staphylococcal Infection	1/68 (1.5%)		0/67 (0%)
Investigations
Blood Albumin Decreased	0/68 (0%)		1/67 (1.5%)
Ejection Fraction Decreased	1/68 (1.5%)		0/67 (0%)
Urine Output Decreased	0/68 (0%)		1/67 (1.5%)
Weight Decreased	1/68 (1.5%)		0/67 (0%)
Metabolism and nutrition disorders
Dehydration	2/68 (2.9%)		1/67 (1.5%)
Anorexia	1/68 (1.5%)		0/67 (0%)
Hyperkalaemia	0/68 (0%)		1/67 (1.5%)
Hyperuricaemia	0/68 (0%)		1/67 (1.5%)
Metabolic Acidosis	1/68 (1.5%)		0/67 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain	0/68 (0%)		1/67 (1.5%)
Pain in Extremity	0/68 (0%)		1/67 (1.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Neoplasm Progression	1/68 (1.5%)		9/67 (13.4%)
Leukaemia	0/68 (0%)		1/67 (1.5%)
Metastases to Abdominal Cavity	1/68 (1.5%)		0/67 (0%)
Non-Hodgkin's Lymphoma	1/68 (1.5%)		0/67 (0%)
Nervous system disorders
Somnolence	1/68 (1.5%)		1/67 (1.5%)
Convulsion	1/68 (1.5%)		1/67 (1.5%)
Depressed level Of Consciousness	0/68 (0%)		1/67 (1.5%)
Dizziness	0/68 (0%)		1/67 (1.5%)
Encephalopathy	1/68 (1.5%)		0/67 (0%)
Grand Mal Convulsion	0/68 (0%)		1/67 (1.5%)
Paraesthesia	1/68 (1.5%)		0/67 (0%)
Status Epilepticus	0/68 (0%)		1/67 (1.5%)
Psychiatric disorders
Depression	1/68 (1.5%)		1/67 (1.5%)
Anxiety	1/68 (1.5%)		0/67 (0%)
Confusional State	0/68 (0%)		1/67 (1.5%)
Suicide Attempt	0/68 (0%)		1/67 (1.5%)
Renal and urinary disorders
Renal Failure	0/68 (0%)		4/67 (6%)
Obstructive Uropathy	0/68 (0%)		1/67 (1.5%)
Oliguria	1/68 (1.5%)		0/67 (0%)
Urinary Incontinence	1/68 (1.5%)		0/67 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	3/68 (4.4%)		2/67 (3%)
Pneumonitis	2/68 (2.9%)		0/67 (0%)
Respiratory Failure	2/68 (2.9%)		2/67 (3%)
Acute Respiratory Distress Syndrome	1/68 (1.5%)		0/67 (0%)
Chronic Obstructive Pulmonary Disease	1/68 (1.5%)		0/67 (0%)
Obstructive Airways disorder	1/68 (1.5%)		1/67 (1.5%)
Pleural Effusion	1/68 (1.5%)		2/67 (3%)
Pulmonary Venous Thrombosis	1/68 (1.5%)		0/67 (0%)
Skin and subcutaneous tissue disorders
Skin Ulcer	1/68 (1.5%)		0/67 (0%)
Vascular disorders
Hypotension	3/68 (4.4%)		2/67 (3%)
Circulatory Collapse	1/68 (1.5%)		0/67 (0%)
Deep Vein Thrombosis	1/68 (1.5%)		1/67 (1.5%)
Other (Not Including Serious) Adverse Events
	Experimental Group		Comparator Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/68 (97.1%)		61/67 (91%)
Blood and lymphatic system disorders
Anemia	21/68 (30.9%)		22/67 (32.8%)
Neutropenia	34/68 (50%)		16/67 (23.9%)
Leukopenia	17/68 (25%)		7/67 (10.4%)
Thrombocytopenia	14/68 (20.6%)		13/67 (19.4%)
Febrile Neutropenia	6/68 (8.8%)		2/67 (3%)
Lymphadenopathy	2/68 (2.9%)		5/67 (7.5%)
Cardiac disorders
Cardiac Disorders	14/68 (20.6%)		9/67 (13.4%)
Gastrointestinal disorders
Nausea	12/68 (17.6%)		11/67 (16.4%)
Abdominal Pain	11/68 (16.2%)		7/67 (10.4%)
Constipation	8/68 (11.8%)		3/67 (4.5%)
Vomiting	5/68 (7.4%)		10/67 (14.9%)
Diarrhea	3/68 (4.4%)		12/67 (17.9%)
General disorders
Asthenia	16/68 (23.5%)		9/67 (13.4%)
Pyrexia	16/68 (23.5%)		16/67 (23.9%)
Edema peripheral	10/68 (14.7%)		4/67 (6%)
Fatigue	9/68 (13.2%)		9/67 (13.4%)
Mucosal inflammation	8/68 (11.8%)		2/67 (3%)
Infections and infestations
Pneumonia	5/68 (7.4%)		4/67 (6%)
Bronchitis	4/68 (5.9%)		0/67 (0%)
Cellulitis	4/68 (5.9%)		2/67 (3%)
Investigations
Ejection fraction decreased	13/68 (19.1%)		7/67 (10.4%)
Weight Decreased	5/68 (7.4%)		5/67 (7.5%)
Platelet count decreased	4/68 (5.9%)		2/67 (3%)
Metabolism and nutrition disorders
Anorexia	8/68 (11.8%)		4/67 (6%)
Dehydration	5/68 (7.4%)		2/67 (3%)
Musculoskeletal and connective tissue disorders
Pain in extremity	5/68 (7.4%)		2/67 (3%)
Back pain	6/68 (8.8%)		2/67 (3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	1/68 (1.5%)		9/67 (13.4%)
Renal and urinary disorders
Chromaturia	4/68 (5.9%)		0/67 (0%)
Renal failure	0/68 (0%)		5/67 (7.5%)
Respiratory, thoracic and mediastinal disorders
Cough	15/68 (22.1%)		3/67 (4.5%)
Dyspnea	9/68 (13.2%)		9/67 (13.4%)
Rhinorrhea	4/68 (5.9%)		0/67 (0%)
Pleural effusion	3/68 (4.4%)		4/67 (6%)
Skin and subcutaneous tissue disorders
Alopecia	9/68 (13.2%)		3/67 (4.5%)
Skin Discoloration	7/68 (10.3%)		0/67 (0%)
Vascular disorders
Hypotension	5/68 (7.4%)		3/67 (4.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.