PIX-R: Comparison of Pixantrone + Rituximab With Gemcitabine + Rituximab in Patients With Aggressive B-cell Non-Hodgkin Lymphoma or Follicular Grade 3 Lymphoma Who Have Relapsed After Therapy and Are Not Eligible for Stem Cell Transplant

• Sponsor: CTI BioPharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01321541
• Collaborator: (none)
• Enrollment: 312
• Locations: 131
• Arms: 2
• Actual Duration (Months): 88.8
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of Pixantrone + Rituximab compared to Gemcitabine + Rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), or follicular grade 3 lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-cell Lymphoma; de Novo DLBCL; DLBCL Transformed From Indolent Lymphoma; Follicular Grade 3 Lymphoma	Drug: Pixantrone + Rituximab; Drug: Gemcitabine + Rituximab	Phase 3

Detailed Description

Eligible patients will be randomized to treatment with pixantrone plus rituximab or gemcitabine plus rituximab in up to six 28-day cycles. At the time patients experience progressive disease during study treatment, early follow- up, or intermediate follow-up, they enter the survival follow up period. Patients who complete study treatment or discontinue study treatment for any other reason will participate in the follow-up periods.

Early Follow-Up: After treatment completion or discontinuation, patient will enter a 24-week follow-up period.

Intermediate Follow-Up: After completing the 24-week early follow-up period, patient will enter an additional 72-week follow-up period.

Survival Follow-Up: All patients will be monitored for survival.

Study Design

• Study Type: Interventional
• Actual Enrollment: 312 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Multicenter Study Comparing Pixantrone + Rituximab With Gemcitabine + Rituximab in Patients With Aggressive B-cell Non-Hodgkin Lymphoma Who Have Relapsed After Therapy With CHOP-R or an Equivalent Regimen and Are Ineligible for Stem Cell Transplant
• Actual Study Start Date: Apr 20, 2011
• Actual Primary Completion Date: Jun 28, 2018
• Actual Study Completion Date: Sep 14, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pixantrone + Rituximab Pixantrone and Rituximab	Drug: Pixantrone + Rituximab; Pixantrone + Rituximab: Rituximab 375 mg/m2 IV on day 1 and pixantrone 50 mg/m2 (equivalent to 85mg/m2 pixantrone dimaleate)IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.
Active Comparator: Gemcitabine + Rituximab Gemcitabine and Rituximab	Drug: Gemcitabine + Rituximab; Gemcitabine + Rituximab: Rituximab 375 mg/m2 IV on day 1 and gemcitabine 1000 mg/m2 IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) [From the date of randomization to the date of progressive disease or death due to any cause (whichever is first reported) (Up to 100 weeks)]

   PFS is defined as the time of randomization to the date of disease progression or death due to any cause (whichever occurs first)

Secondary Outcome Measures

1. Overall Survival [From date of randomization to the date of the patient's death due to any cause (Up to 100 weeks)]

   Overall survival is from randomization to death due to any cause

2. Complete Response Rate [From date of randomization to the date of the patient's death due to any cause (Up to 100 weeks)]

   CRR is defined as the proportion of patients who achieve a Complete Response (CR) without additional therapy. CR is defined as the disappearance of all target lesions.

3. Overall Response Rate [From date of randomization to the date of the patient's death due to any cause (Up to 100 weeks)]

   ORR is defined as the proportion of patients who achieve a CR or PR without additional therapy.

4. Number of Treatment Emergent Adverse Events (TEAE) Related to Study Drug [From date of randomization to the date of the patient's death due to any cause (Up to 100 weeks)]

   The number of Participants with Treatment Emergent Adverse Events (TEAE) related to study drug (pixantrone or gemcitabine)

Other Outcome Measures

1. Individual Concentration-time Profiles of Patients Will be Compared to Existing Data Using Simulations (Visual Predictive Checks) [within 1 hour of initiation of infusion to 24-48 hours after start of pixantrone infusion]

   To characterize the PK profile of pixantrone when co-administered with rituximab. Plasma samples for PK analysis will be collected relative to the D-1 dose of pixantrone in one of the 6 treatment cycles for each participating patient. The goal is to enroll approx. 20 patients, active at 20 sites- Beatson West of Scotland Cancer Center, Uni. Hospital Kralovske Vinohrady, Uni. Hospital Hradec Kralove Hematooncology, Hospital Nuernberg, St. Marien Hospital Hamm, Puerta del Mar Hospital, Tokuda Hospital Sofia, National Center of Hematology & Transfusiology, UMHAT "SV. IVAN RILSKI", Moritz Kaposi General Hospital, Uni. of Debrecen, Polish Red Cross Marine Hospital, Kharkiv Regional Clinical Oncology Center, National Inst. of Cancer Ukraine, Cherkasy Regional Oncology Center, Inst. of Blood Pathology & Transfusion Medicine, Uni. Hospital Martin, National Onclogy Inst., Uni. Hospital with Outpatient Clinic F.D. Roosevelt Banska Bystrica, Uni. Hospital J.A. Reiman Presov

2. To Generate Individual Secondary PK Parameters (eg, Exposure, Half-life Etc.) Using Descriptive Statistics [within 1 hour of initiation of infusion to 24-48 hours after start of pixantrone infusion]

   To characterize the PK profile of pixantrone when co-administered with rituximab. Plasma samples for PK analysis will be collected relative to the D-1 dose of pixantrone in one of the 6 treatment cycles for each participating patient. The goal is to enroll approx. 20 patients, active at 20 sites- Beatson West of Scotland Cancer Center, Uni. Hospital Kralovske Vinohrady, Uni. Hospital Hradec Kralove Hematooncology, Hospital Nuernberg, St. Marien Hospital Hamm, Puerta del Mar Hospital, Tokuda Hospital Sofia, National Center of Hematology & Transfusiology, UMHAT "SV. IVAN RILSKI", Moritz Kaposi General Hospital, Uni. of Debrecen, Polish Red Cross Marine Hospital, Kharkiv Regional Clinical Oncology Center, National Inst. of Cancer Ukraine, Cherkasy Regional Oncology Center, Inst. of Blood Pathology & Transfusion Medicine, Uni. Hospital Martin, National Onclogy Inst., Uni. Hospital with Outpatient Clinic F.D. Roosevelt Banska Bystrica, Uni. Hospital J.A. Reiman Presov

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Diagnosis of DLBCL (de novo DLBCL, or transformed from indolent lymphoma) or follicular grade 3 lymphoma on the basis of tissue biopsy.

2. Patients with de novo DLBCL must have received 1-3 treatment regimens for DLBCL. Patients with follicular grade 3 lymphoma must have received 1-3 treatment regimens for follicular lymphoma (any grade). Patients with DLBCL transformed from indolent lymphoma must have received at least 1-4 treatment regimens for NHL.

3. Received rituximab containing a multi-agent therapy for the treatment of NHL.

4. Not eligible for high-dose chemotherapy and stem cell transplant.

5. Patients with DLBCL transformed from indolent lymphoma must have had a complete or partial response to a therapy for NHL lasting at least 12 weeks.

Exclusion Criteria:

1. Primary refractory de novo DLBCL or primary refractory follicular grade 3 lymphoma, defined as documented progression within 12 weeks of the last cycle of the first-line multi-agent regimen.

2. Prior treatment with cumulative dose of doxorubicin or equivalent exceeding 450 mg/m2

3. Any experimental therapy ≤ 28 days prior to randomization

4. Other malignancy within last 5 years except for the following: curatively treated basal cell/squamous cell skin cancer, carcinoma in situ of the cervix, superficial transitional cell bladder carcinoma, or in situ ductal carcinoma of the breast after complete resection

5. Any contraindication or known allergy or hypersensitivity to any study drugs

6. Concomitant therapy with any anticancer agents, immunosuppressive agents, other investigational anticancer therapies. Low-dose corticosteroids for the treatment of non cancer-related illnesses are permitted.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Clinical Research Center	Tucson	Arizona	United States	85715
2	Arizona Oncology Associates	Tucson	Arizona	United States	85745
3	Highlands Oncology Group	Bentonville	Arkansas	United States	72712
4	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
5	Rocky Mountain Cancer Centers	Aurora	Colorado	United States	80012
6	Rocky Mountain Cancer Centers	Boulder	Colorado	United States	80303
7	Rocky Mountain Cancer Centers	Denver	Colorado	United States	80218
8	George Washington University Department of Medicine	Washington	District of Columbia	United States	20037
9	Integrated Community Oncology Network-St. Vincent's	Jacksonville	Florida	United States	32204
10	Integrated Community Oncology Network-Southside	Jacksonville	Florida	United States	32207
11	Integrated Community Oncology Network	Orange Park	Florida	United States	32073
12	Carle Physician Group	Danville	Illinois	United States	61832
13	Cancer Care Specialists of Central Illinois	Decatur	Illinois	United States	62526
14	Crossroads Cancer Center	Effingham	Illinois	United States	62401
15	Carle Foundation Physician Services	Mattoon	Illinois	United States	61938
16	Carle Cancer Center	Urbana	Illinois	United States	61801
17	Cancer Center of Kansas	Wichita	Kansas	United States	67208
18	Cancer Center of Kansas	Wichita	Kansas	United States	67215
19	Baptist Hospital East	Louisville	Kentucky	United States	40207
20	Harry and Jeanette Weinberg Cancer Institute at Franklin Square	Baltimore	Maryland	United States	21237
21	Center for Cancer and Blood Disorders, PC	Bethesda	Maryland	United States	20817
22	Cancer & Hematology Center of Western Michigan	Grand Rapids	Michigan	United States	49450
23	Metro Minnesota CCOP-Unity Hospital	Fridley	Minnesota	United States	55432
24	Metro Minnesota CCOP-St. Johns	Maplewood	Minnesota	United States	55109
25	Metro Minnesota Community Clinical Oncology Program	Saint Louis Park	Minnesota	United States	55416
26	Metro Minnesota Community Clinical Oncology Program	Saint Louis Park	Minnesota	United States	55426
27	Metro Minnesota CCOP-Regions Hospital	Saint Paul	Minnesota	United States	55101
28	Missouri Cancer Associates	Columbia	Missouri	United States	65201
29	Nebraska Hematology-Oncology, PC	Lincoln	Nebraska	United States	68506
30	Hematology-Oncology Associates of Northern New Jersey	Morristown	New Jersey	United States	07962
31	North Shore Hematology/Oncology Associates	East Setauket	New York	United States	11733
32	Gabrail Cancer Center	Canton	Ohio	United States	44718
33	Gabrail Cancer Center	Dover	Ohio	United States	44622
34	Toledo Clinical Cancer Center	Toledo	Ohio	United States	43617
35	Mercy Cancer Center at St. Anne's	Toledo	Ohio	United States	43623
36	Toledo Clinic Cancer Center-Toledo	Toledo	Ohio	United States	43623
37	Northwest Cancer Specialists, PC	Portland	Oregon	United States	97213
38	Northwest Cancer Specialists, PC	Portland	Oregon	United States	97225
39	Northwest Cancer Specialists, PC	Tualatin	Oregon	United States	97062
40	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
41	Upstate Oncology Associates	Greenville	South Carolina	United States	29615
42	South Carolina Cancer Specialists	Hardeeville	South Carolina	United States	29927
43	South Carolina Cancer Specialists	Hilton Head Island	South Carolina	United States	29926
44	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas	United States	79410
45	Cancer Care Centers of South Texas-HOAST	New Braunfels	Texas	United States	78130
46	Cancer Care Centers of South Texas-HOAST	San Antonio	Texas	United States	78229
47	Blue Ridge Cancer Care	Roanoke	Virginia	United States	24014
48	Northwest Cancer Specialists, PC	Vancouver	Washington	United States	98684
49	Northwest Cancer Specialists, PC	Vancouver	Washington	United States	98686
50	Saint Vincent Hospital Green Bay Oncology	Green Bay	Wisconsin	United States	54301
51	Green Bay Oncology-St. Mary's Hospital MC	Green Bay	Wisconsin	United States	54303
52	Medical University Innsbruck, Department of Internal Medicine V (Hematology and Oncology)	Innsbruck		Austria	6020
53	Hospital Elisabethinen Linz, Internal Department 1 - Hemato-Oncology	Linz		Austria	4020
54	Hanusch Hospital, Department of Internal Medicine III	Vienna		Austria	1140
55	Saint Luc University Hospital, Department of Hematology	Brussels		Belgium	1200
56	General Hospital Delta, Hematology Department	Roeselare		Belgium	8800
57	General Hospital Turnhout, Hematology Department	Turnhout		Belgium	2300
58	UMHAT "Sveti Georgi", Plovdiv, Clinical Hematology Clinic	Plovdiv		Bulgaria	4002
59	UMHAT "Sveti Georgi", Plovdiv, Department of Medical Oncology	Plovdiv		Bulgaria	4002
60	MHAT "Tokuda Hospital Sofia", Hematology Clinic	Sofia		Bulgaria	1407
61	University Multiprofile Hospital for Active Treatment "Sveti Ivan Rilski", Department of Clinical Hematology	Sofia		Bulgaria	1431
62	Specialized Hospital For Active Treatment Of Hematological Diseases, Sofia, Clinical Hematology Clinic	Sofia		Bulgaria	1756
63	MHAT Hristo Botev, Vratsa, First Department of Internal Medicine	Vratsa		Bulgaria	3000
64	University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology	Brno		Czechia	62500
65	University Hospital Hradec Kralove, 4th Department of Internal Medicne, Clinical Hematology	Hradec Kralove		Czechia	500 05
66	University Hospital Ostrava, Institute of Clinical Hematology	Ostrava		Czechia	70852
67	University Hospital Kralovske Vinohrady, Department of Clinical Hematology	Prague		Czechia	10034
68	General University Hospital in Prague, 1st Department of Internal Medicine - Department of Hematology	Prague		Czechia	128 20
69	Aalborg University Hospital, Department of Hematology	Aalborg		Denmark	9100
70	Service d'hématologie clinique, Avenue Laennec Salouel	Amiens, Cedex 1		France	80054
71	Centre hopitalier de la cote basque	Bayonne		France	64190
72	Centre hospitalier de Beziers	Beziers		France	34500
73	Polyclinique de Bordeaux nord Acquitaine	Bordeaux		France	33077
74	Centre hospitalier du Mans	Le Mans Cedex 03		France	72037
75	Centre hospitalier Lyon Sud	Pierre Benite Cedex		France	69495
76	Saint Quentin Hospital Center, Department of Oncology-Hematology	Saint-Quentin		France
77	Hautepierre Hospital, Department of Hematology and Oncology	Strasbourg Cedex		France	97098
78	Gemeinschaftspraxis Drs. Klausmann	Aschaffenburg		Germany	63739
79	Klinikum Chemnitz gGmbH	Chemnitz		Germany	09113
80	Klinik für Innere Medizin III	Frankfurt (a.M.)		Germany	65929
81	Universitaetsklinikum Halle	Halle (Saale)		Germany	06120
82	St. Marien Hospital Hamm	Hamm		Germany	59071
83	Universitätsklinik Köln	Köln		Germany	50924
84	Klinikum Nürnberg Nord	Nürnberg		Germany	90419
85	Klinikum Mutterhaus der Borromäerinnen	Trier		Germany	54290
86	St. Istvan and St. Laszlo Hospital of Budapest	Budapest		Hungary	H-1097
87	University of Debrecen	Debrecen		Hungary	H-4032
88	Moritz Kaposi General Hospital	Kaposvár		Hungary	7400
89	University Hospital "Ospedali Riuniti Umberto I - G.M. Lancisi - G. Salesi"	Ancona		Italy	70126
90	Bologna University Hospital Authority St. Orsola-Malpighi Polyclinic	Bologna		Italy	40138
91	Scientific Institute of Romagna for the Study and Treatment of Cancer (I.R.S.T.) S.R.L.	Meldola		Italy	47014
92	"Ospedali Riuniti Villa Sofia-Cervello" Hospital	Palermo		Italy	90146
93	Romagna Local Health Authority (AUSL Romagna) - "Santa Maria delle Croci"	Ravenna		Italy	48121
94	Romagna Local Health Authority (AUSL Romagna) - "Infermi" Hospital	Rimini		Italy	47900
95	Siena University Hospital Authority Santa Maria alle Scotte Polyclinic	Siena		Italy	53100
96	Santa Maria Hospital	Terni		Italy	5100
97	A.O.U. Città della Salute e della Scienza di Torino	Torino		Italy	10126
98	Independent Public Healthcare Facility Municipal Hospital Group	Chorzów		Poland	41-500
99	Marine Hospital of Polish Red Cross, Department of Chemotheraphy	Gdynia		Poland	81-519
100	Silesia Medical University, Department of Hematology and Bone Marrow Transplantation	Katowice		Poland	40-032
101	Malopolskie Medical Center S.C. , Department of Hematology	Krakow		Poland	30-510
102	Nicolaus Copernicus Memorial Provincial Specialist Hospital in Lodz	Lodz		Poland	93-513
103	Oncology Center of Lublin Land, Department of Clinical Oncology	Lublin		Poland	20-090
104	Institute of Hematology and Transfusion Medicine, Clinic of Hematology	Warsaw		Poland	02-776
105	Wroclaw Medical University, Department and Clinic of Hematology, Blood Neoplasms and Bone Marrow Transplantation	Wroclaw		Poland	50-367
106	Rapid Diagnosis Polyclinic SA	Brasov		Romania
107	Fundeni Clinical Institute Center for Hematology and Bone Marrow Transplantation	Bucharest		Romania	022328
108	Bucharest University Emergency Hospital, Hematology Clinic	Bucharest		Romania	050098
109	State Budget Healthcare Institution of Sverdlovsk region: Sverdlovsk Regional Clinical Hospital #1	Ekaterinburg		Russian Federation	620102
110	Federal State Public Institution: Main Military Clinical Hospital n.a. N.N. Burdenko of the Russian Ministry of Defense	Moscow		Russian Federation	105229
111	Moscow State Budget Medical Institution: City Clinical Hospital n.a. S.P.Botkin	Moscow		Russian Federation
112	State Medical Institution: Republican Hospital named after V.A. Baranov	Petrozavodsk		Russian Federation	18500
113	St. Petersburg Clinical Research and Practical Center for Specialized Types of Medical Care	St. Petersburg		Russian Federation	197758
114	State Healthcare Institution: Republican Clinical Oncology Center	Ufa		Russian Federation	450054
115	University Hospital with Outpatient Clinic F.D. Roosevelt Banska Bystrica, Department of Hematology	Banska Bystrica		Slovakia	975 17
116	National Cancer Institute, Department of Hematology and Transfusiology	Bratislava		Slovakia	83310
117	University Hospital Martin, Department of Hematology and Transfusiology	Martin		Slovakia	3659
118	J. A. Reiman University Hospital with Polyclinic in Presov	Presov		Slovakia	08181
119	A Coruña University Hospital	A Coruña		Spain	15006
120	Hospital Universitario Vall Hebrón	Barcelona		Spain	08035
121	Hospital Iniversitario Puerta del Mar	Cadiz		Spain	11009
122	Institut Català de Oncologia (ICO), Hospital Dr Trueta	Girona		Spain	17007
123	Hospital Iniversitario La Paz	Madrid		Spain	28046
124	Hospital Universitario Araba	Vitoria		Spain	01009
125	Cherkasy Regional Oncology Center, Regional Treatment and Diagnostic Hematology Center	Cherkasy		Ukraine	18009
126	Kharkiv Regional Clinical Oncology Center	Kharkiv		Ukraine	61070
127	National Institute of Cancer	Kyiv		Ukraine	03022
128	State Institution: Institute of Blood Pathology and Transfusion Medicine	Lviv		Ukraine	79044
129	Beatson West of Scotland Cancer Center	Glasgow		United Kingdom	G12 0YN
130	St. George's Healthcare NHS Trust	London		United Kingdom	SW17 0QT
131	Christie Hospital, Department of Medical Oncology	Manchester		United Kingdom	M20 4BX

Sponsors and Collaborators

• CTI BioPharma

Investigators

• Study Director: Simran B Singh, MS, GWCP, Sr. Director, Clinical Operations

Study Documents (Full-Text)

• Study Protocol - Jul 10, 2017
• Statistical Analysis Plan - May 30, 2018

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: CTI BioPharma
• ClinicalTrials.gov Identifier: NCT01321541
• Other Study ID Numbers: PIX306 (PIX-R Trial)
• First Posted: Mar 23, 2011
• Last Update Posted: Nov 19, 2021
• Last Verified: Sep 1, 2021

• Keywords provided by CTI BioPharma: non-hodgkin lymphoma; DLBCL; relapsed; aggressive NHL; Diffuse large B-cell lymphoma; Rituximab; Rituxan; Pixantrone; NHL; non hodgkin's lymphoma; de novo DLBCL; DLBCL transformed from Indolent Lymphoma; Follicular Grade 3 Lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Aggression; Gemcitabine; Rituximab; Pixantrone

Study Results

Participant Flow

Arm/Group Title	Pixantrone + Rituximab	Gemcitabine + Rituximab
Arm/Group Description	Pixantrone and Rituximab Pixantrone + Rituximab: Pixantrone + Rituximab: Rituximab 375 mg/m2 IV on day 1 and pixantrone 50 mg/m2 (equivalent to 85mg/m2 pixantrone dimaleate)IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.	Gemcitabine and Rituximab Gemcitabine + Rituximab: Gemcitabine + Rituximab: Rituximab 375 mg/m2 IV on day 1 and gemcitabine 1000 mg/m2 IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.
Period Title: Overall Study
STARTED	155	157
COMPLETED	72	61
NOT COMPLETED	83	96

Baseline Characteristics

Arm/Group Title	Pixantrone + Rituximab	Gemcitabine + Rituximab	Total
Arm/Group Description	Pixantrone and Rituximab Pixantrone + Rituximab: Pixantrone + Rituximab: Rituximab 375 mg/m2 IV on day 1 and pixantrone 50 mg/m2 (equivalent to 85mg/m2 pixantrone dimaleate)IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.	Gemcitabine and Rituximab Gemcitabine + Rituximab: Gemcitabine + Rituximab: Rituximab 375 mg/m2 IV on day 1 and gemcitabine 1000 mg/m2 IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.	Total of all reporting groups
Overall Participants	155	157	312
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	36 23.2%	30 19.1%	66 21.2%
>=65 years	119 76.8%	127 80.9%	246 78.8%
Sex: Female, Male (Count of Participants)
Female	86 55.5%	90 57.3%	176 56.4%
Male	69 44.5%	67 42.7%	136 43.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 0.6%	1 0.6%	2 0.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 2.6%	1 0.6%	5 1.6%
White	147 94.8%	155 98.7%	302 96.8%
More than one race	2 1.3%	0 0%	2 0.6%
Unknown or Not Reported	1 0.6%	0 0%	1 0.3%
IPI Score (Count of Participants)
IPI Score 0-2	73 47.1%	73 46.5%	146 46.8%
IPI Score 3 or more	82 52.9%	84 53.5%	166 53.2%
Ann Arbor Stage (Count of Participants)
I-III	81 52.3%	76 48.4%	157 50.3%
IV	74 47.7%	81 51.6%	155 49.7%
Number ofprior lines of therapy (Count of Participants)
0-2	137 88.4%	139 88.5%	276 88.5%
3 or more	18 11.6%	18 11.5%	36 11.5%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	PFS is defined as the time of randomization to the date of disease progression or death due to any cause (whichever occurs first)
Time Frame	From the date of randomization to the date of progressive disease or death due to any cause (whichever is first reported) (Up to 100 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pixantrone + Rituximab	Gemcitabine + Rituximab
Arm/Group Description	Pixantrone and Rituximab Pixantrone + Rituximab: Pixantrone + Rituximab: Rituximab 375 mg/m2 IV on day 1 and pixantrone 50 mg/m2 (equivalent to 85mg/m2 pixantrone dimaleate)IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.	Gemcitabine and Rituximab Gemcitabine + Rituximab: Gemcitabine + Rituximab: Rituximab 375 mg/m2 IV on day 1 and gemcitabine 1000 mg/m2 IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.
Measure Participants	155	157
Median (95% Confidence Interval) [Months]	7.3	6.3

2. Secondary Outcome

Title	Overall Survival
Description	Overall survival is from randomization to death due to any cause
Time Frame	From date of randomization to the date of the patient's death due to any cause (Up to 100 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pixantrone + Rituximab	Gemcitabine + Rituximab
Arm/Group Description	Pixantrone and Rituximab Pixantrone + Rituximab: Pixantrone + Rituximab: Rituximab 375 mg/m2 IV on day 1 and pixantrone 50 mg/m2 (equivalent to 85mg/m2 pixantrone dimaleate)IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.	Gemcitabine and Rituximab Gemcitabine + Rituximab: Gemcitabine + Rituximab: Rituximab 375 mg/m2 IV on day 1 and gemcitabine 1000 mg/m2 IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.
Measure Participants	155	157
Median (95% Confidence Interval) [Months]	13.3	19.6

3. Secondary Outcome

Title	Complete Response Rate
Description	CRR is defined as the proportion of patients who achieve a Complete Response (CR) without additional therapy. CR is defined as the disappearance of all target lesions.
Time Frame	From date of randomization to the date of the patient's death due to any cause (Up to 100 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pixantrone + Rituximab	Gemcitabine + Rituximab
Arm/Group Description	Pixantrone and Rituximab Pixantrone + Rituximab: Pixantrone + Rituximab: Rituximab 375 mg/m2 IV on day 1 and pixantrone 50 mg/m2 (equivalent to 85mg/m2 pixantrone dimaleate)IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.	Gemcitabine and Rituximab Gemcitabine + Rituximab: Gemcitabine + Rituximab: Rituximab 375 mg/m2 IV on day 1 and gemcitabine 1000 mg/m2 IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.
Measure Participants	155	157
Count of Participants [Participants]	55 35.5%	34 21.7%

4. Secondary Outcome

Title	Overall Response Rate
Description	ORR is defined as the proportion of patients who achieve a CR or PR without additional therapy.
Time Frame	From date of randomization to the date of the patient's death due to any cause (Up to 100 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pixantrone + Rituximab	Gemcitabine + Rituximab
Arm/Group Description	Pixantrone and Rituximab Pixantrone + Rituximab: Pixantrone + Rituximab: Rituximab 375 mg/m2 IV on day 1 and pixantrone 50 mg/m2 (equivalent to 85mg/m2 pixantrone dimaleate)IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.	Gemcitabine and Rituximab Gemcitabine + Rituximab: Gemcitabine + Rituximab: Rituximab 375 mg/m2 IV on day 1 and gemcitabine 1000 mg/m2 IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.
Measure Participants	155	157
Number (95% Confidence Interval) [percentage of patients]	61.9	43.9

5. Secondary Outcome

Title	Number of Treatment Emergent Adverse Events (TEAE) Related to Study Drug
Description	The number of Participants with Treatment Emergent Adverse Events (TEAE) related to study drug (pixantrone or gemcitabine)
Time Frame	From date of randomization to the date of the patient's death due to any cause (Up to 100 weeks)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Pixantrone + Rituximab	Gemcitabine + Rituximab
Arm/Group Description	Pixantrone and Rituximab Pixantrone + Rituximab: Pixantrone + Rituximab: Rituximab 375 mg/m2 IV on day 1 and pixantrone 50 mg/m2 (equivalent to 85mg/m2 pixantrone dimaleate)IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.	Gemcitabine and Rituximab Gemcitabine + Rituximab: Gemcitabine + Rituximab: Rituximab 375 mg/m2 IV on day 1 and gemcitabine 1000 mg/m2 IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.
Measure Participants	153	146
Count of Participants [Participants]	140 90.3%	140 89.2%

6. Other Pre-specified Outcome

Title	Individual Concentration-time Profiles of Patients Will be Compared to Existing Data Using Simulations (Visual Predictive Checks)
Description	To characterize the PK profile of pixantrone when co-administered with rituximab. Plasma samples for PK analysis will be collected relative to the D-1 dose of pixantrone in one of the 6 treatment cycles for each participating patient. The goal is to enroll approx. 20 patients, active at 20 sites- Beatson West of Scotland Cancer Center, Uni. Hospital Kralovske Vinohrady, Uni. Hospital Hradec Kralove Hematooncology, Hospital Nuernberg, St. Marien Hospital Hamm, Puerta del Mar Hospital, Tokuda Hospital Sofia, National Center of Hematology & Transfusiology, UMHAT "SV. IVAN RILSKI", Moritz Kaposi General Hospital, Uni. of Debrecen, Polish Red Cross Marine Hospital, Kharkiv Regional Clinical Oncology Center, National Inst. of Cancer Ukraine, Cherkasy Regional Oncology Center, Inst. of Blood Pathology & Transfusion Medicine, Uni. Hospital Martin, National Onclogy Inst., Uni. Hospital with Outpatient Clinic F.D. Roosevelt Banska Bystrica, Uni. Hospital J.A. Reiman Presov
Time Frame	within 1 hour of initiation of infusion to 24-48 hours after start of pixantrone infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	To Generate Individual Secondary PK Parameters (eg, Exposure, Half-life Etc.) Using Descriptive Statistics
Description	To characterize the PK profile of pixantrone when co-administered with rituximab. Plasma samples for PK analysis will be collected relative to the D-1 dose of pixantrone in one of the 6 treatment cycles for each participating patient. The goal is to enroll approx. 20 patients, active at 20 sites- Beatson West of Scotland Cancer Center, Uni. Hospital Kralovske Vinohrady, Uni. Hospital Hradec Kralove Hematooncology, Hospital Nuernberg, St. Marien Hospital Hamm, Puerta del Mar Hospital, Tokuda Hospital Sofia, National Center of Hematology & Transfusiology, UMHAT "SV. IVAN RILSKI", Moritz Kaposi General Hospital, Uni. of Debrecen, Polish Red Cross Marine Hospital, Kharkiv Regional Clinical Oncology Center, National Inst. of Cancer Ukraine, Cherkasy Regional Oncology Center, Inst. of Blood Pathology & Transfusion Medicine, Uni. Hospital Martin, National Onclogy Inst., Uni. Hospital with Outpatient Clinic F.D. Roosevelt Banska Bystrica, Uni. Hospital J.A. Reiman Presov
Time Frame	within 1 hour of initiation of infusion to 24-48 hours after start of pixantrone infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From the time of Informed Consent until 30 days after the last dose of study treatment. (Up to 100 weeks)
Adverse Event Reporting Description	Safety will be assessed by monitoring and recording adverse events, serious adverse events, cardiac, hematologic and blood chemistry parameters, vital signs, performance status, and any abnormal findings observed on physical examinations
Arm/Group Title	Pixantrone + Rituximab		Gemcitabine + Rituximab
Arm/Group Description	Pixantrone and Rituximab Pixantrone + Rituximab: Pixantrone + Rituximab: Rituximab 375 mg/m2 IV on day 1 and pixantrone 50 mg/m2 (equivalent to 85mg/m2 pixantrone dimaleate)IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.		Gemcitabine and Rituximab Gemcitabine + Rituximab: Gemcitabine + Rituximab: Rituximab 375 mg/m2 IV on day 1 and gemcitabine 1000 mg/m2 IV on days 1, 8, and 15. Regimen is given in 28-day cycles. Up to 6 cycles may be administered.
All Cause Mortality
	Pixantrone + Rituximab		Gemcitabine + Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/153 (7.8%)		16/149 (10.7%)
Serious Adverse Events
	Pixantrone + Rituximab		Gemcitabine + Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/153 (38.6%)		57/149 (38.3%)
Blood and lymphatic system disorders
Anemia	5/153 (3.3%)	5	8/149 (5.4%)	8
Febrile neutropenia	5/153 (3.3%)	5	1/149 (0.7%)	1
Thrombocytopenia	2/153 (1.3%)	2	3/149 (2%)	3
Leukopenia	1/153 (0.7%)	1	0/149 (0%)	0
Lymphadenopathy	1/153 (0.7%)	1	0/149 (0%)	0
Neutropenia	1/153 (0.7%)	1	1/149 (0.7%)	1
Cardiac disorders
Cardiac failure	3/153 (2%)	3	2/149 (1.3%)	2
Atrial fibrillation	2/153 (1.3%)	2	2/149 (1.3%)	2
Cytotoxic cardiomyopathy	2/153 (1.3%)	2	0/149 (0%)	0
Supraventricular tachycardia	2/153 (1.3%)	2	0/149 (0%)	0
Cardiac failure acute	0/153 (0%)	0	3/149 (2%)	3
Cardiac failure congestive	0/153 (0%)	0	2/149 (1.3%)	2
Acute myocardial infarction	1/153 (0.7%)	1	0/149 (0%)	0
Cardiomyopathy	1/153 (0.7%)	1	0/149 (0%)	0
Myocardial infarction	1/153 (0.7%)	1	1/149 (0.7%)	1
Stress cardiomyopathy	1/153 (0.7%)	1	0/149 (0%)	0
Tachycardia	1/153 (0.7%)	1	1/149 (0.7%)	1
Atrial flutter	0/153 (0%)	0	1/149 (0.7%)	1
Endocrine disorders
Thyroiditis	1/153 (0.7%)	1	0/149 (0%)	0
Eye disorders
Eye pain	1/153 (0.7%)	1	0/149 (0%)	0
Gastrointestinal disorders
Diarrhea	1/153 (0.7%)	1	2/149 (1.3%)	2
Nausea	0/153 (0%)	0	2/149 (1.3%)	2
Constipation	1/153 (0.7%)	1	0/149 (0%)	0
Haemorrhoids	1/153 (0.7%)	1	0/149 (0%)	0
Intestinal perforation	1/153 (0.7%)	1	0/149 (0%)	0
Oesophageal hypomotility	1/153 (0.7%)	1	0/149 (0%)	0
Oesophageal stenosis	1/153 (0.7%)	1	0/149 (0%)	0
Small intestinal obstruction	1/153 (0.7%)	1	0/149 (0%)	0
Abdominal pain	0/153 (0%)	0	1/149 (0.7%)	1
Dysphagia	0/153 (0%)	0	1/149 (0.7%)	1
Large intestine perforation	0/153 (0%)	0	1/149 (0.7%)	1
Upper gastrointestinal haemorrhage	0/153 (0%)	0	1/149 (0.7%)	1
General disorders
Pyrexia	4/153 (2.6%)	4	8/149 (5.4%)	8
Asthenia	2/153 (1.3%)	2	1/149 (0.7%)	1
Chest pain	2/153 (1.3%)	2	1/149 (0.7%)	1
Generalized edema	0/153 (0%)	0	2/149 (1.3%)	2
General physical health deterioration	1/153 (0.7%)	1	1/149 (0.7%)	1
Multi-organ failure	1/153 (0.7%)	1	0/149 (0%)	0
Fatigue	0/153 (0%)	0	1/149 (0.7%)	1
Oedema peripheral	0/153 (0%)	0	1/149 (0.7%)	1
Hepatobiliary disorders
Hepatic cirrhosis	0/153 (0%)	0	1/149 (0.7%)	1
Infections and infestations
Pneumonia	8/153 (5.2%)	8	4/149 (2.7%)	4
Sepsis	2/153 (1.3%)	2	1/149 (0.7%)	1
Septic shock	2/153 (1.3%)	2	0/149 (0%)	0
Urinary tract infection	2/153 (1.3%)	2	3/149 (2%)	3
Staphylococcal bacteremia	1/153 (0.7%)	1	2/149 (1.3%)	2
Cellulitis	0/153 (0%)	0	2/149 (1.3%)	2
Erysipelas	0/153 (0%)	0	3/149 (2%)	3
Upper respiratory tract infection	0/153 (0%)	0	2/149 (1.3%)	2
Catheter related infection	1/153 (0.7%)	1	0/149 (0%)	0
Infection	1/153 (0.7%)	1	0/149 (0%)	0
Neutropenic sepsis	1/153 (0.7%)	1	0/149 (0%)	0
Pleural infection	1/153 (0.7%)	1	0/149 (0%)	0
Pneumonia bacterial	1/153 (0.7%)	1	0/149 (0%)	0
Staphylococcal infection	1/153 (0.7%)	1	1/149 (0.7%)	1
Staphylococcal sepsis	1/153 (0.7%)	1	0/149 (0%)	0
Urinary tract infection bacterial	1/153 (0.7%)	1	0/149 (0%)	0
Wound infection	1/153 (0.7%)	1	0/149 (0%)	0
Bronchitis	0/153 (0%)	0	1/149 (0.7%)	1
Bronchopneumonia	0/153 (0%)	0	1/149 (0.7%)	1
Gastroenteritis	0/153 (0%)	0	1/149 (0.7%)	1
Gastrointestinal bacterial infection	0/153 (0%)	0	1/149 (0.7%)	1
Influenza	0/153 (0%)	0	1/149 (0.7%)	1
Otitis media	0/153 (0%)	0	1/149 (0.7%)	1
Injury, poisoning and procedural complications
Fall	1/153 (0.7%)	1	0/149 (0%)	0
Head injury	1/153 (0.7%)	1	0/149 (0%)	0
Open wound	1/153 (0.7%)	1	0/149 (0%)	0
Overdose	1/153 (0.7%)	1	0/149 (0%)	0
Thrombosis in device	1/153 (0.7%)	1	0/149 (0%)	0
Renal injury	0/153 (0%)	0	1/149 (0.7%)	1
Investigations
Troponin increased	0/153 (0%)	0	1/149 (0.7%)	1
Metabolism and nutrition disorders
Dehydration	2/153 (1.3%)	2	3/149 (2%)	3
Diabetic ketoacidosis	1/153 (0.7%)	1	0/149 (0%)	0
Hypomagnesaemia	1/153 (0.7%)	1	1/149 (0.7%)	1
Hypovolaemia	1/153 (0.7%)	1	0/149 (0%)	0
Lactic acidosis	1/153 (0.7%)	1	0/149 (0%)	0
Anorexia	0/153 (0%)	0	1/149 (0.7%)	1
Hypercalcaemia	0/153 (0%)	0	1/149 (0.7%)	1
Hyperkalaemia	0/153 (0%)	0	1/149 (0.7%)	1
Hypokalaemia	0/153 (0%)	0	1/149 (0.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/153 (0.7%)	1	0/149 (0%)	0
Myalgia	0/153 (0%)	0	1/149 (0.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome	3/153 (2%)	3	0/149 (0%)	0
Acute myelomonocytic leukaemia	1/153 (0.7%)	1	0/149 (0%)	0
Disseminated large cell lymphoma	1/153 (0.7%)	1	0/149 (0%)	0
Squamous cell carcinoma	1/153 (0.7%)	1	1/149 (0.7%)	1
Basal cell carcinoma	0/153 (0%)	0	1/149 (0.7%)	1
Squamous cell carcinoma of skin	0/153 (0%)	0	1/149 (0.7%)	1
Nervous system disorders
Syncope	3/153 (2%)	3	0/149 (0%)	0
Cerebrovascular accident	1/153 (0.7%)	1	1/149 (0.7%)	1
Hypoaesthesia	1/153 (0.7%)	1	0/149 (0%)	0
Lacunar infarction	1/153 (0.7%)	1	0/149 (0%)	0
Lethargy	0/153 (0%)	0	1/149 (0.7%)	1
Restless legs syndrome	0/153 (0%)	0	1/149 (0.7%)	1
Renal and urinary disorders
Hematuria	2/153 (1.3%)	2	2/149 (1.3%)	2
Renal failure acute	2/153 (1.3%)	2	2/149 (1.3%)	2
Hydronephrosis	0/153 (0%)	0	2/149 (1.3%)	2
Cystitis haemorrhagic	1/153 (0.7%)	1	0/149 (0%)	0
Nephrolithiasis	1/153 (0.7%)	1	0/149 (0%)	0
Renal colic	1/153 (0.7%)	1	0/149 (0%)	0
Urinary retention	1/153 (0.7%)	1	0/149 (0%)	0
Nephropathy	0/153 (0%)	0	1/149 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	2/153 (1.3%)	2	0/149 (0%)	0
Dyspnea	2/153 (1.3%)	2	3/149 (2%)	3
Pleural effusion	1/153 (0.7%)	1	2/149 (1.3%)	2
Atelectasis	1/153 (0.7%)	1	0/149 (0%)	0
Lung disorder	1/153 (0.7%)	1	1/149 (0.7%)	1
Pneumonia aspiration	1/153 (0.7%)	1	0/149 (0%)	0
Pulmonary embolism	1/153 (0.7%)	1	1/149 (0.7%)	1
Pulmonary thrombosis	1/153 (0.7%)	1	0/149 (0%)	0
Aspiration	0/153 (0%)	0	1/149 (0.7%)	1
Hypoxia	0/153 (0%)	0	1/149 (0.7%)	1
Pleurisy	0/153 (0%)	0	1/149 (0.7%)	1
Pneumothorax	0/153 (0%)	0	1/149 (0.7%)	1
Pulmonary oedema	0/153 (0%)	0	1/149 (0.7%)	1
Skin and subcutaneous tissue disorders
Decubitus ulcer	0/153 (0%)	0	1/149 (0.7%)	1
Dermatitis allergic	0/153 (0%)	0	1/149 (0.7%)	1
Rash maculo-papular	0/153 (0%)	0	1/149 (0.7%)	1
Vascular disorders
Deep vein thrombosis	1/153 (0.7%)	1	1/149 (0.7%)	1
Hypotension	1/153 (0.7%)	1	0/149 (0%)	0
Lymphoedema	1/153 (0.7%)	1	0/149 (0%)	0
Orthostatic hypotension	1/153 (0.7%)	1	0/149 (0%)	0
Thrombosis	1/153 (0.7%)	1	0/149 (0%)	0
Embolism	0/153 (0%)	0	1/149 (0.7%)	1
Thrombophlebitis	0/153 (0%)	0	1/149 (0.7%)	1
Venous insufficiency	0/153 (0%)	0	1/149 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Pixantrone + Rituximab		Gemcitabine + Rituximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	153/153 (100%)		148/149 (99.3%)
Blood and lymphatic system disorders
Neutropenia	105/153 (68.6%)	105	87/149 (58.4%)	87
Anaemia	37/153 (24.2%)	37	67/149 (45%)	67
Thrombocytopenia	23/153 (15%)	23	95/149 (63.8%)	95
Leukopenia	12/153 (7.8%)	12	19/149 (12.8%)	19
Lymphopenia	10/153 (6.5%)	10	5/149 (3.4%)	5
Gastrointestinal disorders
Nausea	38/153 (24.8%)	38	22/149 (14.8%)	22
Constipation	35/153 (22.9%)	35	20/149 (13.4%)	20
Diarrhoea	23/153 (15%)	23	19/149 (12.8%)	19
Vomiting	21/153 (13.7%)	21	17/149 (11.4%)	17
Stomatitis	16/153 (10.5%)	16	10/149 (6.7%)	10
Abdominal pain	7/153 (4.6%)	7	11/149 (7.4%)	11
General disorders
Fatigue	45/153 (29.4%)	45	34/149 (22.8%)	34
Pyrexia	20/153 (13.1%)	20	30/149 (20.1%)	30
Asthenia	20/153 (13.1%)	20	18/149 (12.1%)	18
Oedema peripheral	19/153 (12.4%)	19	30/149 (20.1%)	30
Chills	11/153 (7.2%)	11	10/149 (6.7%)	10
Infections and infestations
Upper respiratory tract infection	13/153 (8.5%)	13	10/149 (6.7%)	10
Pneumonia	10/153 (6.5%)	10	9/149 (6%)	9
Urinary tract infection	9/153 (5.9%)	9	12/149 (8.1%)	12
Investigations
Weight decreased	12/153 (7.8%)	12	4/149 (2.7%)	4
Ejection fraction decreased	8/153 (5.2%)	8	1/149 (0.7%)	1
Blood creatinine increased	3/153 (2%)	3	10/149 (6.7%)	10
Platelet count decreased	1/153 (0.7%)	1	9/149 (6%)	9
Alanine aminotransferase increased	0/153 (0%)	0	9/149 (6%)	9
Aspartate aminotransferase increased	0/153 (0%)	0	9/149 (6%)	9
Metabolism and nutrition disorders
Anorexia	28/153 (18.3%)	28	16/149 (10.7%)	16
Hypokalaemia	14/153 (9.2%)	14	11/149 (7.4%)	11
Hypomagnesaemia	10/153 (6.5%)	10	6/149 (4%)	6
Dehydration	8/153 (5.2%)	8	4/149 (2.7%)	4
Hyperuricaemia	3/153 (2%)	3	9/149 (6%)	9
Musculoskeletal and connective tissue disorders
Arthralgia	13/153 (8.5%)	13	4/149 (2.7%)	4
Back pain	12/153 (7.8%)	12	10/149 (6.7%)	10
Pain in extremity	10/153 (6.5%)	10	7/149 (4.7%)	7
Hypotension	17/153 (11.1%)	17	6/149 (4%)	6
Hypertension	10/153 (6.5%)	10	10/149 (6.7%)	10
Nervous system disorders
Dizziness	15/153 (9.8%)	15	7/149 (4.7%)	7
Headache	12/153 (7.8%)	12	6/149 (4%)	6
Dysgeusia	11/153 (7.2%)	11	3/149 (2%)	3
Psychiatric disorders
Anxiety	8/153 (5.2%)	8	2/149 (1.3%)	2
Insomnia	6/153 (3.9%)	6	9/149 (6%)	9
Respiratory, thoracic and mediastinal disorders
Dyspnoea	18/153 (11.8%)	18	12/149 (8.1%)	12
Cough	19/153 (12.4%)	19	19/149 (12.8%)	19
Skin and subcutaneous tissue disorders
Alopecia	29/153 (19%)	29	2/149 (1.3%)	2
Skin discolouration	15/153 (9.8%)	15	1/149 (0.7%)	1
Rash	5/153 (3.3%)	5	14/149 (9.4%)	14

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.