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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00088530
Recruitment Status : Completed
First Posted : July 29, 2004
Results First Posted : June 1, 2017
Last Update Posted : November 8, 2018
Sponsor:
Information provided by (Responsible Party):
CTI BioPharma

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Lymphoma, Non-Hodgkin
Interventions Drug: pixantrone, cyclophosphamide, vincristine, rituximab, prednisone
Drug: Vinorelbine, Oxalplatin, Ifosfasmide, Etoposide, Mitoxatrone, Gemcitabine or Rituximab
Enrollment 140
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.
Pre-assignment Details  
Arm/Group Title Experimental Group Comparator Group
Hide 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
Reason Not Completed
Progressive/Relapsed Disease             28             39
Adverse Event             15             9
Withdrawal by Subject             2             5
Lost to Follow-up             2             0
Physician Decision             2             0
Sponsor decision             0             1
Patient never treated             1             0
Arm/Group Title Experimental Group Comparator Group Total
Hide 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 Number of Baseline Participants 70 70 140
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Age at Randomization (years) Number Analyzed 70 participants 70 participants 140 participants
58.2  (13.5) 56.2  (12.9) 57.2  (13.2)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 70 participants 140 participants
18 to < 30
5
   7.1%
2
   2.9%
7
   5.0%
30 to < 40
2
   2.9%
9
  12.9%
11
   7.9%
40 to < 50
9
  12.9%
7
  10.0%
16
  11.4%
50 to < 60
18
  25.7%
21
  30.0%
39
  27.9%
60 to < 70
20
  28.6%
21
  30.0%
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  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 70 participants 140 participants
Female
24
  34.3%
30
  42.9%
54
  38.6%
Male
46
  65.7%
40
  57.1%
86
  61.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 70 participants 140 participants
Caucasian
46
  65.7%
44
  62.9%
90
  64.3%
Black
0
   0.0%
0
   0.0%
0
   0.0%
Asian
10
  14.3%
13
  18.6%
23
  16.4%
Hispanic
7
  10.0%
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   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 70 participants 70 participants 140 participants
North America 4 4 8
Argentina 6 5 11
Bulgaria 6 3 9
Colombia 1 0 1
Ecuador 3 4 7
Hungary 5 5 10
India 9 12 21
Peru 9 8 17
Poland 2 0 2
Romania 1 1 2
Russian Federation 4 5 9
Ukraine 1 3 4
Uruguay 0 1 1
France 4 4 8
United Kingdom 4 3 7
Germany 3 0 3
Italy 8 12 20
[1]
Measure Description: Demographic data will be displayed and summary statistics will be used to describe the study population (i.e., means, medians, and ranges of age, weight, and height, and frequencies for race, gender, baseline performance status, and tumor types and histology). No formal statistical tests will be done.
Baseline ECOG Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 70 participants 140 participants
0
26
  37.1%
23
  32.9%
49
  35.0%
1
30
  42.9%
32
  45.7%
62
  44.3%
2
14
  20.0%
14
  20.0%
28
  20.0%
3
0
   0.0%
1
   1.4%
1
   0.7%
[1]
Measure Description: Eastern Cooperative Oncology Group (ECOG) Performance Status Grade as published in Oken MM, et al. ECOG PS grade 0- Fully active, able to carry on all predisease performance without restriction; 1 - restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, eg, light house work, office work; 2- ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3- capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
1.Primary Outcome
Title Complete Response (CR) and Complete Response Unconfirmed (CRu)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (all randomized patients)
Arm/Group Title Experimental Group Comparator Group
Hide 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
Overall Number of Participants Analyzed 70 70
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of randomized patients
END OF TREATMENT: CR/CRu, n (%)
20.0
(11.4 to 31.3)
5.7
(1.6 to 14.0)
END OF STUDY: CR/CRu, n (%)
24.3
(14.8 to 36.0)
7.1
(2.4 to 15.9)
2.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat patients
Arm/Group Title Experimental Group Comparator Group
Hide 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
Overall Number of Participants Analyzed 70 70
Median (95% Confidence Interval)
Unit of Measure: months
5.3
(2.3 to 6.2)
2.6
(1.9 to 3.5)
3.Secondary Outcome
Title Overall Survival
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-To-Treat (ITT) Population.
Arm/Group Title Experimental Group Comparator Group
Hide 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
Overall Number of Participants Analyzed 70 70
Median (95% Confidence Interval)
Unit of Measure: Months
10.2
(6.4 to 15.7)
7.6
(5.4 to 9.3)
4.Secondary Outcome
Title Overall Response Rate (ORR) Lasting at Least 4 Months
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-To-Treat (ITT) population
Arm/Group Title Experimental Group Comparator Group
Hide 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
Overall Number of Participants Analyzed 70 70
Measure Type: Number
Unit of Measure: participants
12 6
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
Hide 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 (%) Affected / at Risk (%)
Total   49/68 (72.06%)   52/67 (77.61%) 
Show Serious Adverse Events Hide Serious Adverse Events
Experimental Group Comparator Group
Affected / at Risk (%) Affected / at Risk (%)
Total   35/68 (51.47%)   30/67 (44.78%) 
Blood and lymphatic system disorders     
Neutropenia * 1  9/68 (13.24%)  6/67 (8.96%) 
Thrombocytopenia * 2  1/68 (1.47%)  6/67 (8.96%) 
Anemia * 2  2/68 (2.94%)  5/67 (7.46%) 
Febrile neutropenia * 2  4/68 (5.88%)  2/67 (2.99%) 
Leukopenia * 2  4/68 (5.88%)  2/67 (2.99%) 
Lymphadenopathy * 2  0/68 (0.00%)  1/67 (1.49%) 
Pancytopenia * 2  0/68 (0.00%)  1/67 (1.49%) 
Cardiac disorders     
Cardiac Failure * 2  2/68 (2.94%)  1/67 (1.49%) 
Cardiac Failure Congestive * 2  2/68 (2.94%)  0/67 (0.00%) 
Cardiac Arrest * 2  1/68 (1.47%)  0/67 (0.00%) 
Cyanosis * 2  1/68 (1.47%)  0/67 (0.00%) 
Myocardial Ischaemia * 2  1/68 (1.47%)  0/67 (0.00%) 
Myocarditis * 2  0/68 (0.00%)  1/67 (1.49%) 
Pericardial Effusion * 2  1/68 (1.47%)  0/67 (0.00%) 
Sinus Tachycardia * 2  0/68 (0.00%)  1/67 (1.49%) 
Tachycardia * 2  1/68 (1.47%)  0/67 (0.00%) 
Ventricular Extrasystoles * 2  0/68 (0.00%)  1/67 (1.49%) 
Eye disorders     
Keratitis * 2  1/68 (1.47%)  0/67 (0.00%) 
Gastrointestinal disorders     
Abdominal Pain * 2  3/68 (4.41%)  3/67 (4.48%) 
Vomiting * 2  0/68 (0.00%)  2/67 (2.99%) 
Abdominal Distension * 2  0/68 (0.00%)  1/67 (1.49%) 
Diarrhoea * 2  0/68 (0.00%)  1/67 (1.49%) 
Dysphagia * 2  0/68 (0.00%)  1/67 (1.49%) 
Ileus * 2  1/68 (1.47%)  0/67 (0.00%) 
Nausea * 2  0/68 (0.00%)  1/67 (1.49%) 
General disorders     
Pyrexia * 2  7/68 (10.29%)  7/67 (10.45%) 
Asthenia * 2  1/68 (1.47%)  1/67 (1.49%) 
Oedema Peripheral * 2  1/68 (1.47%)  1/67 (1.49%) 
Fatigue * 2  0/68 (0.00%)  1/67 (1.49%) 
Generalised Oedema * 2  0/68 (0.00%)  1/67 (1.49%) 
Mucosal Inflammation * 2  0/68 (0.00%)  1/67 (1.49%) 
Multi-organ Failure * 2  1/68 (1.47%)  0/67 (0.00%) 
Non-cardiac Chest pain * 2  1/68 (1.47%)  0/67 (0.00%) 
Performance Status Decreased * 2  0/68 (0.00%)  1/67 (1.49%) 
Hepatobiliary disorders     
Cholestasis * 2  1/68 (1.47%)  0/67 (0.00%) 
Jaundice * 2  1/68 (1.47%)  0/67 (0.00%) 
Infections and infestations     
Pneumonia * 2  5/68 (7.35%)  4/67 (5.97%) 
Cellulitis * 2  2/68 (2.94%)  2/67 (2.99%) 
Bronchitis * 2  2/68 (2.94%)  0/67 (0.00%) 
Sepsis * 2  1/68 (1.47%)  1/67 (1.49%) 
Septic Shock * 2  2/68 (2.94%)  0/67 (0.00%) 
Candiddiasis * 2  1/68 (1.47%)  0/67 (0.00%) 
Catheter realted infection * 2  1/68 (1.47%)  0/67 (0.00%) 
Escherichia Urinary Tract Infection * 2  0/68 (0.00%)  1/67 (1.49%) 
Gastroenteristic Salmonella * 2  1/68 (1.47%)  0/67 (0.00%) 
Gastrointestinal Infection * 2  0/68 (0.00%)  1/67 (1.49%) 
Herpes Virus Infection * 2  1/68 (1.47%)  0/67 (0.00%) 
Neutropenic Sepsis * 2  0/68 (0.00%)  1/67 (1.49%) 
Pharyngitis * 2  0/68 (0.00%)  1/67 (1.49%) 
Postoperative Wound Infection * 2  0/68 (0.00%)  1/67 (1.49%) 
Staphylococcal Infection * 2  1/68 (1.47%)  0/67 (0.00%) 
Investigations     
Blood Albumin Decreased * 2  0/68 (0.00%)  1/67 (1.49%) 
Ejection Fraction Decreased * 2  1/68 (1.47%)  0/67 (0.00%) 
Urine Output Decreased * 2  0/68 (0.00%)  1/67 (1.49%) 
Weight Decreased * 2  1/68 (1.47%)  0/67 (0.00%) 
Metabolism and nutrition disorders     
Dehydration * 2  2/68 (2.94%)  1/67 (1.49%) 
Anorexia * 2  1/68 (1.47%)  0/67 (0.00%) 
Hyperkalaemia * 2  0/68 (0.00%)  1/67 (1.49%) 
Hyperuricaemia * 2  0/68 (0.00%)  1/67 (1.49%) 
Metabolic Acidosis * 2  1/68 (1.47%)  0/67 (0.00%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal Pain * 2  0/68 (0.00%)  1/67 (1.49%) 
Pain in Extremity * 2  0/68 (0.00%)  1/67 (1.49%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant Neoplasm Progression * 2  1/68 (1.47%)  9/67 (13.43%) 
Leukaemia * 2  0/68 (0.00%)  1/67 (1.49%) 
Metastases to Abdominal Cavity * 2  1/68 (1.47%)  0/67 (0.00%) 
Non-Hodgkin's Lymphoma * 2  1/68 (1.47%)  0/67 (0.00%) 
Nervous system disorders     
Somnolence * 2  1/68 (1.47%)  1/67 (1.49%) 
Convulsion * 2  1/68 (1.47%)  1/67 (1.49%) 
Depressed level Of Consciousness * 2  0/68 (0.00%)  1/67 (1.49%) 
Dizziness * 2  0/68 (0.00%)  1/67 (1.49%) 
Encephalopathy * 2  1/68 (1.47%)  0/67 (0.00%) 
Grand Mal Convulsion * 2  0/68 (0.00%)  1/67 (1.49%) 
Paraesthesia * 2  1/68 (1.47%)  0/67 (0.00%) 
Status Epilepticus * 2  0/68 (0.00%)  1/67 (1.49%) 
Psychiatric disorders     
Depression * 2  1/68 (1.47%)  1/67 (1.49%) 
Anxiety * 2  1/68 (1.47%)  0/67 (0.00%) 
Confusional State * 2  0/68 (0.00%)  1/67 (1.49%) 
Suicide Attempt * 2  0/68 (0.00%)  1/67 (1.49%) 
Renal and urinary disorders     
Renal Failure * 2  0/68 (0.00%)  4/67 (5.97%) 
Obstructive Uropathy * 2  0/68 (0.00%)  1/67 (1.49%) 
Oliguria * 2  1/68 (1.47%)  0/67 (0.00%) 
Urinary Incontinence * 2  1/68 (1.47%)  0/67 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 2  3/68 (4.41%)  2/67 (2.99%) 
Pneumonitis * 2  2/68 (2.94%)  0/67 (0.00%) 
Respiratory Failure * 2  2/68 (2.94%)  2/67 (2.99%) 
Acute Respiratory Distress Syndrome * 2  1/68 (1.47%)  0/67 (0.00%) 
Chronic Obstructive Pulmonary Disease * 2  1/68 (1.47%)  0/67 (0.00%) 
Obstructive Airways disorder * 2  1/68 (1.47%)  1/67 (1.49%) 
Pleural Effusion * 2  1/68 (1.47%)  2/67 (2.99%) 
Pulmonary Venous Thrombosis * 2  1/68 (1.47%)  0/67 (0.00%) 
Skin and subcutaneous tissue disorders     
Skin Ulcer * 2  1/68 (1.47%)  0/67 (0.00%) 
Vascular disorders     
Hypotension * 2  3/68 (4.41%)  2/67 (2.99%) 
Circulatory Collapse * 2  1/68 (1.47%)  0/67 (0.00%) 
Deep Vein Thrombosis * 2  1/68 (1.47%)  1/67 (1.49%) 
1
Term from vocabulary, NCI CTCAE v 3
2
Term from vocabulary, MedDRA (11.1)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Experimental Group Comparator Group
Affected / at Risk (%) Affected / at Risk (%)
Total   66/68 (97.06%)   61/67 (91.04%) 
Blood and lymphatic system disorders     
Anemia * 1  21/68 (30.88%)  22/67 (32.84%) 
Neutropenia * 1  34/68 (50.00%)  16/67 (23.88%) 
Leukopenia * 1  17/68 (25.00%)  7/67 (10.45%) 
Thrombocytopenia * 1  14/68 (20.59%)  13/67 (19.40%) 
Febrile Neutropenia * 1  6/68 (8.82%)  2/67 (2.99%) 
Lymphadenopathy * 1  2/68 (2.94%)  5/67 (7.46%) 
Cardiac disorders     
Cardiac Disorders * 1 [1]  14/68 (20.59%)  9/67 (13.43%) 
Gastrointestinal disorders     
Nausea * 1  12/68 (17.65%)  11/67 (16.42%) 
Abdominal Pain * 1  11/68 (16.18%)  7/67 (10.45%) 
Constipation * 1  8/68 (11.76%)  3/67 (4.48%) 
Vomiting * 1  5/68 (7.35%)  10/67 (14.93%) 
Diarrhea * 1  3/68 (4.41%)  12/67 (17.91%) 
General disorders     
Asthenia * 1  16/68 (23.53%)  9/67 (13.43%) 
Pyrexia * 1  16/68 (23.53%)  16/67 (23.88%) 
Edema peripheral * 1  10/68 (14.71%)  4/67 (5.97%) 
Fatigue * 1  9/68 (13.24%)  9/67 (13.43%) 
Mucosal inflammation * 1  8/68 (11.76%)  2/67 (2.99%) 
Infections and infestations     
Pneumonia * 1  5/68 (7.35%)  4/67 (5.97%) 
Bronchitis * 1  4/68 (5.88%)  0/67 (0.00%) 
Cellulitis * 1  4/68 (5.88%)  2/67 (2.99%) 
Investigations     
Ejection fraction decreased * 1  13/68 (19.12%)  7/67 (10.45%) 
Weight Decreased * 1  5/68 (7.35%)  5/67 (7.46%) 
Platelet count decreased * 1  4/68 (5.88%)  2/67 (2.99%) 
Metabolism and nutrition disorders     
Anorexia * 1  8/68 (11.76%)  4/67 (5.97%) 
Dehydration * 1  5/68 (7.35%)  2/67 (2.99%) 
Musculoskeletal and connective tissue disorders     
Pain in extremity * 1  5/68 (7.35%)  2/67 (2.99%) 
Back pain * 1  6/68 (8.82%)  2/67 (2.99%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant neoplasm progression * 1  1/68 (1.47%)  9/67 (13.43%) 
Renal and urinary disorders     
Chromaturia * 1  4/68 (5.88%)  0/67 (0.00%) 
Renal failure * 1  0/68 (0.00%)  5/67 (7.46%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  15/68 (22.06%)  3/67 (4.48%) 
Dyspnea * 1  9/68 (13.24%)  9/67 (13.43%) 
Rhinorrhea * 1  4/68 (5.88%)  0/67 (0.00%) 
Pleural effusion * 1  3/68 (4.41%)  4/67 (5.97%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  9/68 (13.24%)  3/67 (4.48%) 
Skin Discoloration * 1  7/68 (10.29%)  0/67 (0.00%) 
Vascular disorders     
Hypotension * 2  5/68 (7.35%)  3/67 (4.48%) 
1
Term from vocabulary, MedDRA (11.1)
2
Term from vocabulary, MedDRA (10.0)
*
Indicates events were collected by non-systematic assessment
[1]
Cardiac AEs are presented as a grouping within the SOC of Cardiac Disorders as no specific preferred term was reported > 5%. PTs include, but are not limited to, cardiac failure, left ventricular dysfunction and ejection fraction decreased.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Results Point of Contact
Name/Title: Simran Bedi Singh
Organization: CTIBioPharma Corp.
Phone: (206) 272-4000
Responsible Party: CTI BioPharma
ClinicalTrials.gov Identifier: NCT00088530     History of Changes
Obsolete Identifiers: NCT00101049
Other Study ID Numbers: PIX301
First Submitted: July 28, 2004
First Posted: July 29, 2004
Results First Submitted: March 11, 2017
Results First Posted: June 1, 2017
Last Update Posted: November 8, 2018