Fludarabine and Thalidomide in Treating Patients With Newly Diagnosed Chronic Lymphocytic Leukemia

• Sponsor: Roswell Park Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00096018
• Collaborator: (none)
• Enrollment: 43
• Location: 1
• Arm: 1
• Duration (Months): 120
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Biological therapies such as thalidomide use different ways to stimulate the immune system and stop cancer cells from growing. Combining fludarabine with thalidomide may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of thalidomide when given together with fludarabine and to see how well they work in treating patients with newly diagnosed B-cell chronic lymphocytic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: fludarabine phosphate; Drug: thalidomide	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

• Determine the safety and efficacy of fludarabine and thalidomide in patients with newly diagnosed B-cell chronic lymphocytic leukemia.

• Determine the overall response rate (complete and partial) in patients treated with this regimen.

• Determine the duration of response in patients treated with this regimen.

OUTLINE: This is an open-label, phase I, dose-escalation study of thalidomide followed by a phase II study.

• Phase I: Beginning on day 1, patients receive oral thalidomide once daily for up to 6 months. Beginning on day 7, patients also receive fludarabine IV over 30 minutes daily for 5 days. Treatment with fludarabine repeats every 28-35 days for up to 6 courses. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of thalidomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients receive fludarabine and thalidomide as in phase I at the MTD.

Patients are followed at 4 weeks, every 3 months for 2 years, and then every 4 months for 2 years.

PROJECTED ACCRUAL: Up to 45 patients (≥ 9 for the phase I portion and ≤ 36 for the phase II portion) will be accrued for this study within 8 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study of Fludarabine Plus Thalidomide as Frontline Therapy for Newly Diagnosed Patients With Chronic Lymphocytic Leukemia
• Study Start Date: May 1, 2002
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose escalation Thalidomide (100 mg/day, 200 mg/day, or 300 mg/day) on Day 1 followed by Fludarabine 25 mg/m2/day for 5 days starting on Day 7 (cycle = 28 days	Drug: fludarabine phosphate; Given IV; Drug: thalidomide; Orally

Outcome Measures

Primary Outcome Measures

1. Overall Responders (Complete and Partial Response) [4 weeks, every 3 months for 2 years, and then every 4 months for 2 years]

   Criteria for response were based on the Revised National Cancer Institute-sponsored Working Group Guidelines for response, which includes clinical, hematologic, and bone marrow features (Cheson, B.D., et al., National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996;87:4990-97.)

2. Duration of Response [4 weeks, every 3 months for 2 years, and then every 4 months for 2 years]

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Confirmed diagnosis of B-cell chronic lymphocytic leukemia (CLL) based on the following criteria:

• Peripheral blood lymphocytosis > 5,000/mm^3

• Co-expression of CD5, CD19 or CD20, and CD23 surface antigens

• Clonal kappa or lambda light chain expression

• No recurrent or refractory CLL

• No other lymphoproliferative diseases or diseases due to transformation of CLL, such as prolymphocytic leukemia or Richter's syndrome

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• At least 12 weeks

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin < 1.5 mg/dL

• AST < 2.5 times upper limit of normal

Renal

• Creatinine ≤ 1.5 mg/dL

Cardiovascular

• No cardiac arrhythmia within the past 6 months

• No myocardial infarction within the past 6 months

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use at least 1 highly active and 1 additional method of contraception for 4 weeks before, during, and for at least 4 weeks after study treatment

• Patients must have sufficient mental capacity to understand the study explanation and provide informed consent

• No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix

• No active serious infection uncontrolled by antibiotics

• No medical condition or reason that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No prior therapy for CLL

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001

Sponsors and Collaborators

• Roswell Park Cancer Institute

Investigators

• Principal Investigator: Kelvin Lee, MD, Roswell Park Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT00096018
• Other Study ID Numbers: CDR0000391769; RPC-01-12
• First Posted: Nov 9, 2004
• Last Update Posted: Oct 24, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by Roswell Park Cancer Institute: stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; B-cell chronic lymphocytic leukemia
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Thalidomide; Fludarabine; Fludarabine phosphate

Study Results

Participant Flow

Recruitment Details	Study Activated: 3/21/2002. Study Closed: 11/19/2010

Arm/Group Title	Phase I - Dose Escalation	Phase II
Arm/Group Description	Thalidomide (100 mg/day, 200 mg/day, or 300 mg/day) on Day 1 followed by Fludarabine 25 mg/m2/day for 5 days starting on Day 7 (cycle = 28 days)	Thalidomide 200 mg/day on Day 1 followed by Fludarabine 25 mg/m2/day for 5 days starting on Day 7 (cycle = 28 days)
Period Title: Overall Study
STARTED	13	30
Treated With Study Therapy	13	25
COMPLETED	11	16
NOT COMPLETED	2	14

Baseline Characteristics

Arm/Group Title	Phase I - Dose Escalation	Phase II	Total
Arm/Group Description	Thalidomide (100 mg/day, 200 mg/day, or 300 mg/day) on Day 1 followed by Fludarabine 25 mg/m2/day for 5 days starting on Day 7 (cycle = 28 days)	Thalidomide 200 mg/day on Day 1 followed by Fludarabine 25 mg/m2/day for 5 days starting on Day 7 (cycle = 28 days)	Total of all reporting groups
Overall Participants	13	25	38
Age, Customized (participants) [Number]
30 - 39 years	2 15.4%	0 0%	2 5.3%
40 - 49 years	1 7.7%	2 8%	3 7.9%
50 - 59 years	2 15.4%	8 32%	10 26.3%
60 - 69 years	5 38.5%	9 36%	14 36.8%
70 - 79 years	3 23.1%	6 24%	9 23.7%
Sex: Female, Male (Count of Participants)
Female	4 30.8%	7 28%	11 28.9%
Male	9 69.2%	18 72%	27 71.1%
Region of Enrollment (participants) [Number]
United States	13 100%	25 100%	38 100%

Outcome Measures

1. Primary Outcome

Title	Overall Responders (Complete and Partial Response)
Description	Criteria for response were based on the Revised National Cancer Institute-sponsored Working Group Guidelines for response, which includes clinical, hematologic, and bone marrow features (Cheson, B.D., et al., National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996;87:4990-97.)
Time Frame	4 weeks, every 3 months for 2 years, and then every 4 months for 2 years

Outcome Measure Data

Analysis Population Description

All Treated Patients

Arm/Group Title	Phase I - Dose Escalation	Phase II
Arm/Group Description	Thalidomide (100 mg/day, 200 mg/day, or 300 mg/day) on Day 1 followed by Fludarabine 25 mg/m2/day for 5 days starting on Day 7 (cycle = 28 days)	Thalidomide 200 mg/day on Day 1 followed by Fludarabine 25 mg/m2/day for 5 days starting on Day 7 (cycle = 28 days)
Measure Participants	13	25
Number [participants]	8 61.5%	18 72%

2. Primary Outcome

Title	Duration of Response
Time Frame	4 weeks, every 3 months for 2 years, and then every 4 months for 2 years

Outcome Measure Data

Analysis Population Description

Patients with Complete or Partial Response

Arm/Group Title	Phase I - Dose Escalation	Phase II
Arm/Group Description	Thalidomide (100 mg/day, 200 mg/day, or 300 mg/day) on Day 1 followed by Fludarabine 25 mg/m2/day for 5 days starting on Day 7 (cycle = 28 days)	Thalidomide 200 mg/day on Day 1 followed by Fludarabine 25 mg/m2/day for 5 days starting on Day 7 (cycle = 28 days)
Measure Participants	8	18
Mean (Standard Deviation) [months]	43.3 (11.3)	30.0 (16.4)

Adverse Events

Arm/Group Title	Phase I - Dose Escalation		Phase II
Arm/Group Description	Thalidomide (100 mg/day, 200 mg/day, or 300 mg/day) on Day 1 followed by Fludarabine 25 mg/m2/day for 5 days starting on Day 7 (cycle = 28 days)		Thalidomide 200 mg/day on Day 1 followed by Fludarabine 25 mg/m2/day for 5 days starting on Day 7 (cycle = 28 days)
All Cause Mortality
	Phase I - Dose Escalation		Phase II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Phase I - Dose Escalation		Phase II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/13 (46.2%)		15/25 (60%)
Blood and lymphatic system disorders
Anaemia - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Anaemia - Grade 3	0/13 (0%)	0	1/25 (4%)	1
Anaemia - Grade 4	0/13 (0%)	0	1/25 (4%)	1
Febrile neutropenia - Grade 2	1/13 (7.7%)	1	0/25 (0%)	0
Febrile neutropenia - Grade 3	2/13 (15.4%)	2	3/25 (12%)	3
Febrile neutropenia - Grade 4	0/13 (0%)	0	1/25 (4%)	1
Leukopenia - Grade 3	0/13 (0%)	0	1/25 (4%)	1
Neutropenia - Grade 3	1/13 (7.7%)	1	0/25 (0%)	0
Neutropenia - Grade 4	0/13 (0%)	0	1/25 (4%)	1
Thrombocytopenia - Grade 4	0/13 (0%)	0	2/25 (8%)	2
Cardiac disorders
Angina pectoris - Grade 4	0/13 (0%)	0	1/25 (4%)	1
General disorders
Death - Grade 5	0/13 (0%)	0	1/25 (4%)	1
Fatigue - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Fatigue - Grade 3	1/13 (7.7%)	1	0/25 (0%)	0
Oedema peripheral - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Pyrexia - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Immune system disorders
Hypersensitivity - Grade 3	0/13 (0%)	0	1/25 (4%)	1
Infections and infestations
Pneumonia - Grade 3	0/13 (0%)	0	3/25 (12%)	3
Upper respiratory tract infection - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Upper respiratory tract infection - Grade 3	1/13 (7.7%)	1	0/25 (0%)	0
Injury, poisoning and procedural complications
Femur fracture - Grade 3	0/13 (0%)	0	1/25 (4%)	1
Investigations
Liver function test abnormal - Grade 4	1/13 (7.7%)	1	0/25 (0%)	0
Metabolism and nutrition disorders
Decreased appetite - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Failure to thrive - Grade 3	0/13 (0%)	0	1/25 (4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour lysis syndrome - Grade 3	0/13 (0%)	0	2/25 (8%)	2
Nervous system disorders
Dysgeusia - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea - Grade 3	0/13 (0%)	0	1/25 (4%)	1
Pleural effusion - Grade 3	0/13 (0%)	0	2/25 (8%)	2
Pulmonary embolism - Grade 3	1/13 (7.7%)	1	1/25 (4%)	1
Skin and subcutaneous tissue disorders
Rash - Grade 3	0/13 (0%)	0	2/25 (8%)	2
Rash erythematous - Grade 4	0/13 (0%)	0	1/25 (4%)	1
Rash generalised - Grade 2	0/13 (0%)	0	2/25 (8%)	2
Surgical and medical procedures
Coronary artery bypass - Grade 4	0/13 (0%)	0	1/25 (4%)	1
Vascular disorders
Deep vein thrombosis - Grade 3	0/13 (0%)	0	1/25 (4%)	1
Other (Not Including Serious) Adverse Events
	Phase I - Dose Escalation		Phase II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/13 (69.2%)		25/25 (100%)
Blood and lymphatic system disorders
Anaemia - Grade 1	0/13 (0%)	0	5/25 (20%)	5
Anaemia - Grade 2	0/13 (0%)	0	2/25 (8%)	2
Anaemia - Grade 3	1/13 (7.7%)	1	1/25 (4%)	1
Granulocytopenia - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Leukopenia - Grade 3	0/13 (0%)	0	3/25 (12%)	3
Lymphadenopathy - Grade 2	1/13 (7.7%)	1	0/25 (0%)	0
Lymphopenia - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Lymphopenia - Grade 2	0/13 (0%)	0	2/25 (8%)	2
Lymphopenia - Grade 3	0/13 (0%)	0	2/25 (8%)	2
Neutropenia - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Neutropenia - Grade 2	0/13 (0%)	0	2/25 (8%)	2
Neutropenia - Grade 3	2/13 (15.4%)	4	5/25 (20%)	7
Neutropenia - Grade 4	2/13 (15.4%)	3	3/25 (12%)	3
Pancytopenia - Grade 1	1/13 (7.7%)	1	0/25 (0%)	0
Thrombocytopenia - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Thrombocytopenia - Grade 2	0/13 (0%)	0	3/25 (12%)	3
Thrombocytopenia - Grade 3	0/13 (0%)	0	5/25 (20%)	5
Cardiac disorders
Bradycardia - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Ear and labyrinth disorders
Ear pain - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Ear pain - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Eye disorders
Diplopia - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Eye swelling - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Vision blurred - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Vision blurred - Grade 2	0/13 (0%)	0	2/25 (8%)	2
Visual disturbance - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Gastrointestinal disorders
Abdominal discomfort - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Abdominal distension - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Abdominal pain upper - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Abdominal tenderness - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Constipation - Grade 1	2/13 (15.4%)	2	5/25 (20%)	5
Constipation - Grade 2	0/13 (0%)	0	4/25 (16%)	4
Diarrhoea - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Diarrhoea - Grade 3	1/13 (7.7%)	2	0/25 (0%)	0
Dry mouth - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Dysphagia - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Flatulence - Grade 1	0/13 (0%)	0	1/25 (4%)	2
Hypoaesthesia oral - Grade 1	0/13 (0%)	0	2/25 (8%)	3
Nausea - Grade 1	2/13 (15.4%)	2	4/25 (16%)	4
Nausea - Grade 2	0/13 (0%)	0	2/25 (8%)	2
Paraesthesia oral - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Vomiting - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Vomiting - Grade 2	0/13 (0%)	0	1/25 (4%)	1
General disorders
Asthenia - Grade 1	1/13 (7.7%)	1	4/25 (16%)	4
Asthenia - Grade 2	0/13 (0%)	0	2/25 (8%)	2
Asthenia - Grade 3	0/13 (0%)	0	1/25 (4%)	1
Chest pain - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Chest pain - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Chills - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Face oedema - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Fatigue - Grade 1	2/13 (15.4%)	2	11/25 (44%)	13
Fatigue - Grade 2	1/13 (7.7%)	1	3/25 (12%)	3
Fatigue - Grade 3	0/13 (0%)	0	3/25 (12%)	3
Gait disturbance - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Generalised oedema - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Influenza like illness - Grade 2	0/13 (0%)	0	2/25 (8%)	2
Non-cardiac chest pain - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Oedema - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Oedema - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Oedema peripheral - Grade 1	2/13 (15.4%)	2	7/25 (28%)	8
Oedema peripheral - Grade 2	1/13 (7.7%)	1	2/25 (8%)	2
Pain - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Pain - Grade 2	0/13 (0%)	0	2/25 (8%)	3
Pain - Grade 3	0/13 (0%)	0	1/25 (4%)	1
Pyrexia - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Temperature intolerance - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Tenderness - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Hepatobiliary disorders
Hyperbilirubinaemia - Grade 1	0/13 (0%)	0	1/25 (4%)	2
Hyperbilirubinaemia - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Immune system disorders
Hypersensitivity - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Infections and infestations
Candidiasis - Grade 1	1/13 (7.7%)	1	0/25 (0%)	0
Ear infection - Grade 1	1/13 (7.7%)	1	0/25 (0%)	0
Fungal infection - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Herpes simplex - Grade 1	1/13 (7.7%)	1	0/25 (0%)	0
Influenza - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Nasopharyngitis - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Nasopharyngitis - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Oral candidiasis - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Pneumonia - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Sinusitis - Grade 1	1/13 (7.7%)	1	0/25 (0%)	0
Upper respiratory tract infection - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Upper respiratory tract infection - Grade 2	2/13 (15.4%)	2	1/25 (4%)	1
Injury, poisoning and procedural complications
Sunburn - Grade 1	1/13 (7.7%)	1	0/25 (0%)	0
Thermal burn - Grade 1	1/13 (7.7%)	1	0/25 (0%)	0
Investigations
Activated partial thromboplastin time prolonged - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Activated partial thromboplastin time prolonged - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Alanine aminotransferase increased - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Aspartate aminotransferase increased - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Blood albumin decreased - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Blood bicarbonate decreased - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Blood chloride increased - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Blood creatine increased - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Blood creatinine increased - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Blood creatinine increased - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Blood creatinine increased - Grade 3	0/13 (0%)	0	1/25 (4%)	1
Blood phosphorus - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Blood potassium increased - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Blood urea increased - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Blood uric acid increased - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Haemoglobin decreased - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Haemoglobin decreased - Grade 3	1/13 (7.7%)	2	0/25 (0%)	0
Hepatic enzyme increased - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Hepatic enzyme increased - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Liver function test abnormal - Grade 2	1/13 (7.7%)	1	0/25 (0%)	0
Neutrophil count decreased - Grade 2	0/13 (0%)	0	2/25 (8%)	3
Neutrophil count decreased - Grade 4	0/13 (0%)	0	2/25 (8%)	2
Platelet count decreased - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Platelet count decreased - Grade 3	0/13 (0%)	0	3/25 (12%)	3
Protein total decreased - Grade 1	0/13 (0%)	0	3/25 (12%)	3
Protein total decreased - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Prothrombin level abnormal - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Weight decreased - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Weight decreased - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Weight increased - Grade 1	0/13 (0%)	0	1/25 (4%)	1
White blood cell count decreased - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Metabolism and nutrition disorders
Anorexia - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Decreased appetite - Grade 1	0/13 (0%)	0	4/25 (16%)	5
Decreased appetite - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Dehydration - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Fluid retention - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Hyperglycaemia - Grade 1	0/13 (0%)	0	5/25 (20%)	5
Hyperglycaemia - Grade 3	1/13 (7.7%)	1	0/25 (0%)	0
Hyperkalaemia - Grade 1	0/13 (0%)	0	3/25 (12%)	4
Hyperkalaemia - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Hypermagnesaemia - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Hyperphosphataemia - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Hyperphosphataemia - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Hyperuricaemia - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Hypoalbuminaemia - Grade 1	0/13 (0%)	0	4/25 (16%)	4
Hypoalbuminaemia - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Hypocalcaemia - Grade 1	0/13 (0%)	0	4/25 (16%)	4
Hypocalcaemia - Grade 2	0/13 (0%)	0	3/25 (12%)	3
Hypocalcaemia - Grade 3	0/13 (0%)	0	1/25 (4%)	1
Hypoglycaemia - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Hypokalaemia - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Hypokalaemia - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Hyponatraemia - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Hyponatraemia - Grade 3	0/13 (0%)	0	1/25 (4%)	1
Hypoproteinaemia - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Musculoskeletal and connective tissue disorders
Arthralgia - Grade 1	0/13 (0%)	0	3/25 (12%)	3
Arthralgia - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Back pain - Grade 1	0/13 (0%)	0	3/25 (12%)	3
Back pain - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Bone pain - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Flank pain - Grade 1	1/13 (7.7%)	1	1/25 (4%)	1
Flank pain - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Muscle spasms - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Musculoskeletal discomfort - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Pain in extremity - Grade 1	1/13 (7.7%)	1	1/25 (4%)	1
Pain in jaw - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour flare - Grade 1	0/13 (0%)	0	5/25 (20%)	5
Tumour flare - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Nervous system disorders
Amnesia - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Convulsion - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Disturbance in attention - Grade 1	1/13 (7.7%)	1	1/25 (4%)	1
Dizziness - Grade 1	2/13 (15.4%)	3	7/25 (28%)	8
Dizziness - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Dizziness - Grade 3	0/13 (0%)	0	1/25 (4%)	1
Dizziness postural - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Headache - Grade 1	0/13 (0%)	0	3/25 (12%)	3
Headache - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Hypoaesthesia - Grade 1	1/13 (7.7%)	1	2/25 (8%)	4
Hypoaesthesia - Grade 2	0/13 (0%)	0	1/25 (4%)	2
Memory impairment - Grade 1	1/13 (7.7%)	1	0/25 (0%)	0
Neuropathy - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Neuropathy peripheral - Grade 1	0/13 (0%)	0	5/25 (20%)	6
Paraesthesia - Grade 1	2/13 (15.4%)	3	0/25 (0%)	0
Sinus headache - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Somnolence - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Tremor - Grade 1	1/13 (7.7%)	2	5/25 (20%)	6
Psychiatric disorders
Anxiety - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Confusional state - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Depression - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Depression - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Insomnia - Grade 1	1/13 (7.7%)	1	2/25 (8%)	2
Insomnia - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Mood swings - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Renal and urinary disorders
Renal failure - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Urinary retention - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
Asthma - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Cough - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Dysphonia - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Dyspnoea - Grade 1	2/13 (15.4%)	2	4/25 (16%)	4
Dyspnoea - Grade 2	0/13 (0%)	0	3/25 (12%)	3
Dyspnoea exertional - Grade 1	2/13 (15.4%)	2	1/25 (4%)	1
Nasal congestion - Grade 1	1/13 (7.7%)	1	0/25 (0%)	0
Pharyngolaryngeal pain - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Pneumonitis - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Productive cough - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Pulmonary hypertension - Grade 3	0/13 (0%)	0	1/25 (4%)	1
Skin and subcutaneous tissue disorders
Dry skin - Grade 1	0/13 (0%)	0	2/25 (8%)	2
Erythema - Grade 1	1/13 (7.7%)	1	1/25 (4%)	1
Hypoaesthesia facial - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Nail disorder - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Night sweats - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Night sweats - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Petechiae - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Pruritus - Grade 1	0/13 (0%)	0	5/25 (20%)	6
Pruritus - Grade 2	0/13 (0%)	0	2/25 (8%)	2
Pruritus generalised - Grade 2	0/13 (0%)	0	2/25 (8%)	2
Rash - Grade 1	3/13 (23.1%)	3	6/25 (24%)	7
Rash - Grade 2	0/13 (0%)	0	1/25 (4%)	1
Rash generalised - Grade 1	1/13 (7.7%)	1	5/25 (20%)	5
Rash generalised - Grade 2	1/13 (7.7%)	1	0/25 (0%)	0
Rash generalised - Grade 3	1/13 (7.7%)	1	1/25 (4%)	2
Rash pruritic - Grade 1	1/13 (7.7%)	1	1/25 (4%)	1
Rash pruritic - Grade 3	0/13 (0%)	0	1/25 (4%)	1
Skin exfoliation - Grade 1	1/13 (7.7%)	1	0/25 (0%)	0
Skin hyperpigmentation - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Skin odour abnormal - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Swelling face - Grade 1	0/13 (0%)	0	1/25 (4%)	1
Vascular disorders
Hypotension - Grade 1	0/13 (0%)	0	1/25 (4%)	1

Limitations/Caveats

The study was stopped early due to low accrual.

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.