Lenalidomide With or Without Rituximab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

• Sponsor: Roswell Park Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00096044
• Collaborator: Celgene (Industry)
• Enrollment: 45
• Location: 1
• Arm: 1
• Duration (Months): 135
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Biological therapies such as lenalidomide use different ways to stimulate the immune system and stop cancer cells from growing. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining lenalidomide with rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying the how well giving lenalidomide with or without rituximab works in treating patients with relapsed or refractory chronic lymphocytic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: rituximab; Drug: lenalidomide	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the best cytostatic response rate (including complete response, partial response, or stable disease) in patients with relapsed or refractory chronic lymphocytic leukemia treated with lenalidomide (CC-5013).

Secondary

• Determine the cytostatic response rate in patients who progress on CC-5013 and are then treated with CC-5013 and rituximab.

• Determine the safety of these regimens in these patients.

• Determine time to progression in patients treated with these regimens.

OUTLINE: This is an open-label, non-randomized, pilot study.

Patients receive oral lenalidomide (CC-5013) once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (CR) receive 2 additional courses beyond CR.

Patients with disease progression receive oral CC-5013 once daily on days 1-21 and rituximab IV on days 1, 8, and 15 during the first treatment course and on days 1 and 15 of all subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of further disease progression. Patients who achieve CR receive 2 additional courses beyond CR.

Patients are followed at 1 month and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study within 1.5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: CC-5013 Alone or in Combination With Rituximab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
• Study Start Date: Mar 1, 2004
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oral Lenalidomide Patients receive oral lenalidomide (CC-5013) once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity	Biological: rituximab; IV; Drug: lenalidomide; Oral

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients Achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) on Single Agent CC-5013 at 6 Months [at 6 Months]

   Percentage of patients achieving CR, PR or maintaining SD using the 1996 NCI-WF Criteria. CR: absence of lymph nodes and constitutional symptoms; no hepatomegaly or splenomegaly by physical examination; neutrophil count >1500/μL; platelet count >100,000/μL; untransfused hemoglobin concentration >11.0g/dL; lymphocyte count <4000/μL; bone marrow sample must be at least normocellular for age; with less than 30% of nucleated cells being lymphocytes and no lymphoid nodules. PR: ≥50% decrease in lymphocyte count from baseline; ≥50% reduction in lymph nodes from baseline; ≥50% reduction in the size of the liver/spleen from baseline; neutrophil count ≥1500/μL or ≥50% improvement from baseline; platelet count ≥100,000/μL or ≥50% improvement from baseline; untransfused hemoglobin concentration ≥11.0g/dL or ≥50% improvement from baseline. Patients have not exhibited as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow, are considered to have SD.

Secondary Outcome Measures

1. Percentage of Patients Achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) on Combination Therapy of CC-5013+Rituximab [5 years]

   Percentage of patients achieving CR, PR or maintaining SD using the 1996 NCI-WF Criteria. CR: absence of lymph nodes and constitutional symptoms; no hepatomegaly or splenomegaly by physical examination; neutrophil count >1500/μL; platelet count >100,000/μL; untransfused hemoglobin concentration >11.0g/dL; lymphocyte count <4000/μL; bone marrow sample must be at least normocellular for age; with less than 30% of nucleated cells being lymphocytes and no lymphoid nodules. PR: ≥50% decrease in lymphocyte count from baseline; ≥50% reduction in lymph nodes from baseline; ≥50% reduction in the size of the liver/spleen from baseline; neutrophil count ≥1500/μL or ≥50% improvement from baseline; platelet count ≥100,000/μL or ≥50% improvement from baseline; untransfused hemoglobin concentration ≥11.0g/dL or ≥50% improvement from baseline. Patients who have not exhibited as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow, are considered to have SD.

2. Number of Participants With Adverse Events on Single Agent CC-5013 [1 year]

   Number of Participants with Adverse Events on Single Agent CC-5013, Graded According to NCI CTCAE Version 3.0 Please refer to the adverse event reporting for more detail.

3. Number of Participants With Adverse Events on Combination Therapy of CC-5013+Rituximab [Up to 30 days from last date of institution of combination therapy of CC-5013+Rituximab.]

   Number of Participants with Adverse Events on Combination Therapy of CC-5013+Rituximab, Graded According to NCI CTCAE Version 3.0

4. Time to Progression for Single Agent CC-5013 [5 years]

   Progressive disease is defined as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow using the 1996 NCI-WF Criteria.

5. Time to Progression for the Combination Therapy of CC-5013+Rituximab [Every month up to 6 months and every 3 months thereafter up to 5 years]

   Progressive disease is defined as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow using the 1996 NCI-WF Criteria.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Diagnosis of chronic lymphocytic leukemia (CLL) by flow cytometry

• Relapsed or refractory disease

• Measurable disease, defined by 1 of the following criteria:

• Absolute lymphocyte count ≥ 5,000/mm^3

• Measurable lymphadenopathy or organomegaly

• Received ≥ 1 prior therapy for CLL

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 30,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 mg/dL

• AST and ALT ≤ 2 times upper limit of normal (ULN) (5 times ULN if hepatic metastases are present)

Renal

• Creatinine ≤ 1.5 mg/dL

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective double-method (including barrier) contraception during and for 3 months after study participation

• No known hypersensitivity to thalidomide

• No erythema nodosum characterized by a desquamating rash after prior thalidomide or similar drug administration

• No known anaphylaxis or immunoglobulin E-mediated hypersensitivity to murine proteins

• No serious medical condition or laboratory abnormality that would preclude study participation

• No psychiatric illness that would preclude giving informed consent

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior lenalidomide (CC-5013)

• No concurrent thalidomide

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• At least 4 weeks since prior therapy for CLL

• At least 28 days since prior experimental drug or therapy

• No other concurrent anticancer therapies

• No other concurrent investigational agents

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
• Celgene

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: NCT00096044
• Other Study ID Numbers: CDR0000391767; RPCI-I-18103; CELGENE-RV-CLL-PI-005
• First Posted: Nov 9, 2004
• Last Update Posted: Jul 11, 2017
• Last Verified: Jun 1, 2017

• Keywords provided by Roswell Park Cancer Institute: refractory chronic lymphocytic leukemia
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Rituximab; Lenalidomide

Study Results

Participant Flow

Arm/Group Title	Oral Lenalidomide
Arm/Group Description	Patients receive oral lenalidomide (CC-5013) once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity rituximab: IV lenalidomide: Oral
Period Title: Overall Study
STARTED	45
COMPLETED	11
NOT COMPLETED	34

Baseline Characteristics

Arm/Group Title	Oral Lenalidomide
Arm/Group Description	Patients receive oral lenalidomide (CC-5013) once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity rituximab: IV lenalidomide: Oral
Overall Participants	45
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.1 (7.9)
Sex: Female, Male (Count of Participants)
Female	9 20%
Male	36 80%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients Achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) on Single Agent CC-5013 at 6 Months
Description	Percentage of patients achieving CR, PR or maintaining SD using the 1996 NCI-WF Criteria. CR: absence of lymph nodes and constitutional symptoms; no hepatomegaly or splenomegaly by physical examination; neutrophil count >1500/μL; platelet count >100,000/μL; untransfused hemoglobin concentration >11.0g/dL; lymphocyte count <4000/μL; bone marrow sample must be at least normocellular for age; with less than 30% of nucleated cells being lymphocytes and no lymphoid nodules. PR: ≥50% decrease in lymphocyte count from baseline; ≥50% reduction in lymph nodes from baseline; ≥50% reduction in the size of the liver/spleen from baseline; neutrophil count ≥1500/μL or ≥50% improvement from baseline; platelet count ≥100,000/μL or ≥50% improvement from baseline; untransfused hemoglobin concentration ≥11.0g/dL or ≥50% improvement from baseline. Patients have not exhibited as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow, are considered to have SD.
Time Frame	at 6 Months

Outcome Measure Data

Analysis Population Description

All treated and eligible patients

Arm/Group Title	Oral Lenalidomide
Arm/Group Description	Patients receive oral lenalidomide (CC-5013) once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity rituximab: IV lenalidomide: Oral
Measure Participants	45
Number (95% Confidence Interval) [percentage of participants]	68.9 153.1%

2. Secondary Outcome

Title	Percentage of Patients Achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) on Combination Therapy of CC-5013+Rituximab
Description	Percentage of patients achieving CR, PR or maintaining SD using the 1996 NCI-WF Criteria. CR: absence of lymph nodes and constitutional symptoms; no hepatomegaly or splenomegaly by physical examination; neutrophil count >1500/μL; platelet count >100,000/μL; untransfused hemoglobin concentration >11.0g/dL; lymphocyte count <4000/μL; bone marrow sample must be at least normocellular for age; with less than 30% of nucleated cells being lymphocytes and no lymphoid nodules. PR: ≥50% decrease in lymphocyte count from baseline; ≥50% reduction in lymph nodes from baseline; ≥50% reduction in the size of the liver/spleen from baseline; neutrophil count ≥1500/μL or ≥50% improvement from baseline; platelet count ≥100,000/μL or ≥50% improvement from baseline; untransfused hemoglobin concentration ≥11.0g/dL or ≥50% improvement from baseline. Patients who have not exhibited as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow, are considered to have SD.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

All treated with combination therapy of CC-5013+Rituximab and eligible patients

Arm/Group Title	Oral Lenalidomide
Arm/Group Description	Patients receive oral lenalidomide (CC-5013) once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity rituximab: IV lenalidomide: Oral
Measure Participants	8
Number (95% Confidence Interval) [percentage of participants]	100 222.2%

3. Secondary Outcome

Title	Number of Participants With Adverse Events on Single Agent CC-5013
Description	Number of Participants with Adverse Events on Single Agent CC-5013, Graded According to NCI CTCAE Version 3.0 Please refer to the adverse event reporting for more detail.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

All treated and eligible patients

Arm/Group Title	Oral Lenalidomide
Arm/Group Description	Patients receive oral lenalidomide (CC-5013) once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity rituximab: IV lenalidomide: Oral
Measure Participants	45
Grade 1	0 0%
Grade 2	3 6.7%
Grade 3	7 15.6%
Grade 4	33 73.3%
Grade 5	2 4.4%

4. Secondary Outcome

Title	Number of Participants With Adverse Events on Combination Therapy of CC-5013+Rituximab
Description	Number of Participants with Adverse Events on Combination Therapy of CC-5013+Rituximab, Graded According to NCI CTCAE Version 3.0
Time Frame	Up to 30 days from last date of institution of combination therapy of CC-5013+Rituximab.

Outcome Measure Data

Analysis Population Description

All treated with combination therapy of CC-5013+Rituximab and eligible patients

Arm/Group Title	Oral Lenalidomide
Arm/Group Description	Patients receive oral lenalidomide (CC-5013) once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity rituximab: IV lenalidomide: Oral
Measure Participants	8
Grade 1	1 2.2%
Grade 2	0 0%
Grade 3	3 6.7%
Grade 4	3 6.7%

5. Secondary Outcome

Title	Time to Progression for Single Agent CC-5013
Description	Progressive disease is defined as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow using the 1996 NCI-WF Criteria.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

All treated and eligible patients

Arm/Group Title	Oral Lenalidomide
Arm/Group Description	Patients receive oral lenalidomide (CC-5013) once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity rituximab: IV lenalidomide: Oral
Measure Participants	45
Median (95% Confidence Interval) [months]	23.0

6. Secondary Outcome

Title	Time to Progression for the Combination Therapy of CC-5013+Rituximab
Description	Progressive disease is defined as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow using the 1996 NCI-WF Criteria.
Time Frame	Every month up to 6 months and every 3 months thereafter up to 5 years

Outcome Measure Data

Analysis Population Description

All treated with combination therapy of CC-5013+Rituximab and eligible patients

Arm/Group Title	Oral Lenalidomide
Arm/Group Description	Patients receive oral lenalidomide (CC-5013) once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity rituximab: IV lenalidomide: Oral
Measure Participants	8
Median (95% Confidence Interval) [months]	18.7

Adverse Events

Arm/Group Title	Oral Lenalidomide
Arm/Group Description	Patients receive oral lenalidomide (CC-5013) once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity rituximab: IV lenalidomide: Oral
All Cause Mortality
	Oral Lenalidomide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Oral Lenalidomide
	Affected / at Risk (%)	# Events
Total	29/45 (64.4%)
Blood and lymphatic system disorders
Anaemia	4/45 (8.9%)	5
Febrile neutropenia	11/45 (24.4%)	16
Neutropenia	5/45 (11.1%)	6
Thrombocytopenia	4/45 (8.9%)	4
Cardiac disorders
Cardio-respiratory arrest	2/45 (4.4%)	2
Myocardial ischaemia	1/45 (2.2%)	1
Palpitations	1/45 (2.2%)	1
Gastrointestinal disorders
Diarrhoea	1/45 (2.2%)	1
Nausea	1/45 (2.2%)	1
General disorders
Chest pain	3/45 (6.7%)	3
Chills	1/45 (2.2%)	1
Death	2/45 (4.4%)	2
Fatigue	1/45 (2.2%)	1
Pyrexia	3/45 (6.7%)	3
Hepatobiliary disorders
Hyperbilirubinaemia	1/45 (2.2%)	1
Infections and infestations
Bacteraemia	1/45 (2.2%)	1
Device related infection	1/45 (2.2%)	1
Diverticulitis	1/45 (2.2%)	1
Herpes simplex	1/45 (2.2%)	1
Herpes zoster	1/45 (2.2%)	1
Infection	2/45 (4.4%)	3
Lobar pneumonia	1/45 (2.2%)	1
Pneumonia	12/45 (26.7%)	15
Pseudomonal bacteraemia	1/45 (2.2%)	1
Sepsis	2/45 (4.4%)	2
Sinusitis	1/45 (2.2%)	1
Skin infection	1/45 (2.2%)	1
Staphylococcal infection	1/45 (2.2%)	1
Upper respiratory tract infection	2/45 (4.4%)	2
Injury, poisoning and procedural complications
Collapse of lung	1/45 (2.2%)	1
Investigations
Breath sounds abnormal	1/45 (2.2%)	1
Metabolism and nutrition disorders
Hypercalcaemia	1/45 (2.2%)	1
Hypocalcaemia	1/45 (2.2%)	1
Hyponatraemia	1/45 (2.2%)	1
Tumour lysis syndrome	1/45 (2.2%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/45 (2.2%)	1
Back pain	1/45 (2.2%)	1
Bone pain	1/45 (2.2%)	1
Musculoskeletal discomfort	1/45 (2.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour flare	3/45 (6.7%)	3
Psychiatric disorders
Confusional state	1/45 (2.2%)	1
Mental status changes	1/45 (2.2%)	1
Renal and urinary disorders
Renal failure	1/45 (2.2%)	1
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/45 (2.2%)	1
Cough	1/45 (2.2%)	1
Dyspnoea	3/45 (6.7%)	4
Hypoxia	1/45 (2.2%)	1
Laryngospasm	1/45 (2.2%)	1
Pleural effusion	3/45 (6.7%)	5
Pneumonitis	1/45 (2.2%)	1
Pulmonary embolism	3/45 (6.7%)	3
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/45 (2.2%)	1
Surgical and medical procedures
Intestinal anastomosis	1/45 (2.2%)	1
Vascular disorders
Deep vein thrombosis	2/45 (4.4%)	2
Other (Not Including Serious) Adverse Events
	Oral Lenalidomide
	Affected / at Risk (%)	# Events
Total	44/45 (97.8%)
Blood and lymphatic system disorders
Anaemia	35/45 (77.8%)	51
Anaemia haemolytic autoimmune	1/45 (2.2%)	1
Febrile neutropenia	1/45 (2.2%)	1
Haemolytic anaemia	1/45 (2.2%)	1
Leukopenia	20/45 (44.4%)	44
Lymph node pain	1/45 (2.2%)	1
Lymphadenopathy	1/45 (2.2%)	1
Lymphopenia	6/45 (13.3%)	7
Neutropenia	41/45 (91.1%)	128
Splenomegaly	1/45 (2.2%)	1
Thrombocytopenia	41/45 (91.1%)	79
Cardiac disorders
Bradycardia	3/45 (6.7%)	3
Cardiac failure congestive	2/45 (4.4%)	2
Cardiac flutter	1/45 (2.2%)	1
Myocardial ischaemia	1/45 (2.2%)	1
Tachycardia	1/45 (2.2%)	1
Ventricular extrasystoles	1/45 (2.2%)	1
Ear and labyrinth disorders
Cerumen impaction	1/45 (2.2%)	1
Ear congestion	1/45 (2.2%)	1
Ear discomfort	2/45 (4.4%)	2
Ear pain	2/45 (4.4%)	2
Vertigo	1/45 (2.2%)	2
Eye disorders
Cataract	2/45 (4.4%)	2
Eye irritation	1/45 (2.2%)	1
Eye oedema	2/45 (4.4%)	2
Lacrimation increased	3/45 (6.7%)	3
Ocular hyperaemia	1/45 (2.2%)	1
Periorbital oedema	1/45 (2.2%)	2
Photopsia	1/45 (2.2%)	1
Scleral discolouration	1/45 (2.2%)	1
Vision blurred	6/45 (13.3%)	7
Visual impairment	1/45 (2.2%)	1
Gastrointestinal disorders
Abdominal discomfort	2/45 (4.4%)	3
Abdominal distension	11/45 (24.4%)	13
Abdominal pain	10/45 (22.2%)	12
Abdominal pain lower	1/45 (2.2%)	1
Abdominal pain upper	5/45 (11.1%)	6
Abdominal tenderness	1/45 (2.2%)	1
Aphthous stomatitis	2/45 (4.4%)	2
Cheilitis	1/45 (2.2%)	1
Colitis	1/45 (2.2%)	1
Colitis ulcerative	1/45 (2.2%)	1
Constipation	19/45 (42.2%)	21
Diarrhoea	24/45 (53.3%)	44
Dry mouth	3/45 (6.7%)	3
Dyspepsia	3/45 (6.7%)	4
Dysphagia	3/45 (6.7%)	3
Eructation	2/45 (4.4%)	2
Flatulence	2/45 (4.4%)	2
Gastritis	1/45 (2.2%)	1
Gingival pain	1/45 (2.2%)	1
Gingivitis	1/45 (2.2%)	1
Glossodynia	1/45 (2.2%)	1
Hypoaesthesia oral	1/45 (2.2%)	1
Lip pain	1/45 (2.2%)	1
Lip swelling	1/45 (2.2%)	1
Nausea	16/45 (35.6%)	17
Odynophagia	1/45 (2.2%)	1
Oral discomfort	1/45 (2.2%)	1
Oral pain	2/45 (4.4%)	2
Painful defaecation	1/45 (2.2%)	1
Stomatitis	1/45 (2.2%)	1
Tongue coated	2/45 (4.4%)	2
Toothache	1/45 (2.2%)	1
Vomiting	11/45 (24.4%)	12
General disorders
Asthenia	23/45 (51.1%)	28
Axillary pain	1/45 (2.2%)	1
Chest pain	5/45 (11.1%)	7
Chills	1/45 (2.2%)	1
Crepitations	2/45 (4.4%)	2
Early satiety	1/45 (2.2%)	1
Effusion	1/45 (2.2%)	1
Facial pain	1/45 (2.2%)	1
Fatigue	43/45 (95.6%)	70
Feeling abnormal	1/45 (2.2%)	1
Feeling hot	2/45 (4.4%)	2
Influenza like illness	4/45 (8.9%)	4
Irritability	1/45 (2.2%)	1
Local swelling	1/45 (2.2%)	1
Malaise	2/45 (4.4%)	2
Oedema	11/45 (24.4%)	13
Oedema peripheral	16/45 (35.6%)	26
Pain	3/45 (6.7%)	5
Pyrexia	16/45 (35.6%)	18
Tenderness	1/45 (2.2%)	1
Thirst	1/45 (2.2%)	1
Hepatobiliary disorders
Hepatic function abnormal	1/45 (2.2%)	1
Hyperbilirubinaemia	11/45 (24.4%)	19
Jaundice	1/45 (2.2%)	1
Immune system disorders
Hypersensitivity	1/45 (2.2%)	1
Infections and infestations
Bronchitis	2/45 (4.4%)	2
Cellulitis	2/45 (4.4%)	2
Clostridial infection	1/45 (2.2%)	1
Ear infection	1/45 (2.2%)	1
Eye infection staphylococcal	1/45 (2.2%)	1
Fungal infection	4/45 (8.9%)	4
Helicobacter gastritis	1/45 (2.2%)	1
Herpes simplex	1/45 (2.2%)	2
Herpes zoster	2/45 (4.4%)	2
Herpes zoster disseminated	1/45 (2.2%)	1
Infection	2/45 (4.4%)	2
Nasopharyngitis	6/45 (13.3%)	6
Opportunistic infection	1/45 (2.2%)	1
Oral candidiasis	3/45 (6.7%)	3
Otitis media	1/45 (2.2%)	1
Pharyngitis	2/45 (4.4%)	2
Pneumonia	5/45 (11.1%)	6
Respiratory tract infection	3/45 (6.7%)	4
Rhinitis	1/45 (2.2%)	1
Sinusitis	10/45 (22.2%)	18
Tooth abscess	2/45 (4.4%)	2
Tooth infection	1/45 (2.2%)	1
Upper respiratory tract infection	12/45 (26.7%)	35
Urinary tract infection	1/45 (2.2%)	1
Viral infection	2/45 (4.4%)	2
Viral upper respiratory tract infection	1/45 (2.2%)	1
Vulvovaginal mycotic infection	1/45 (2.2%)	1
Injury, poisoning and procedural complications
Contusion	9/45 (20%)	10
Muscle strain	1/45 (2.2%)	1
Splenosis	1/45 (2.2%)	1
Tendon injury	1/45 (2.2%)	1
Thermal burn	1/45 (2.2%)	1
Wound	1/45 (2.2%)	1
Investigations
Activated partial thromboplastin time prolonged	1/45 (2.2%)	2
Alanine aminotransferase increased	14/45 (31.1%)	27
Aspartate aminotransferase	1/45 (2.2%)	1
Aspartate aminotransferase decreased	7/45 (15.6%)	7
Aspartate aminotransferase increased	15/45 (33.3%)	26
Blood alkaline phosphatase increased	18/45 (40%)	18
Blood bilirubin increased	3/45 (6.7%)	5
Blood creatine decreased	2/45 (4.4%)	2
Blood creatinine	4/45 (8.9%)	4
Blood creatinine decreased	3/45 (6.7%)	3
Blood creatinine increased	3/45 (6.7%)	5
Blood glucose increased	1/45 (2.2%)	1
Blood phosphorus	4/45 (8.9%)	4
Blood phosphorus decreased	1/45 (2.2%)	1
Blood phosphorus increased	1/45 (2.2%)	1
Blood potassium decreased	1/45 (2.2%)	1
Blood pressure increased	1/45 (2.2%)	1
Blood urea decreased	4/45 (8.9%)	4
Blood urea increased	15/45 (33.3%)	15
Blood uric acid decreased	5/45 (11.1%)	5
Blood uric acid increased	3/45 (6.7%)	3
Breath sounds abnormal	2/45 (4.4%)	2
Immunoglobulins decreased	1/45 (2.2%)	1
Liver function test abnormal	2/45 (4.4%)	3
Platelet count decreased	2/45 (4.4%)	3
Protein total decreased	1/45 (2.2%)	1
Prothrombin time prolonged	1/45 (2.2%)	3
Troponin	1/45 (2.2%)	1
Weight decreased	13/45 (28.9%)	15
Weight increased	1/45 (2.2%)	1
pH urine abnormal	1/45 (2.2%)	1
Metabolism and nutrition disorders
Cachexia	1/45 (2.2%)	1
Decreased appetite	17/45 (37.8%)	19
Dehydration	1/45 (2.2%)	1
Hypercalcaemia	1/45 (2.2%)	2
Hyperglycaemia	12/45 (26.7%)	16
Hyperkalaemia	11/45 (24.4%)	14
Hypermagnesaemia	1/45 (2.2%)	1
Hypernatraemia	7/45 (15.6%)	7
Hyperphosphataemia	7/45 (15.6%)	7
Hyperproteinaemia	1/45 (2.2%)	1
Hyperuricaemia	1/45 (2.2%)	1
Hypoalbuminaemia	20/45 (44.4%)	31
Hypocalcaemia	27/45 (60%)	43
Hypoglycaemia	3/45 (6.7%)	5
Hypokalaemia	17/45 (37.8%)	20
Hypomagnesaemia	1/45 (2.2%)	1
Hyponatraemia	20/45 (44.4%)	22
Hypophagia	1/45 (2.2%)	1
Hypophosphataemia	5/45 (11.1%)	5
Hypoproteinaemia	21/45 (46.7%)	21
Hypouricaemia	3/45 (6.7%)	4
Tumour lysis syndrome	1/45 (2.2%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	9/45 (20%)	9
Back pain	9/45 (20%)	12
Bone pain	2/45 (4.4%)	3
Flank pain	1/45 (2.2%)	1
Groin pain	2/45 (4.4%)	2
Joint swelling	1/45 (2.2%)	1
Limb discomfort	1/45 (2.2%)	1
Muscle spasms	8/45 (17.8%)	19
Muscle tightness	1/45 (2.2%)	1
Muscular weakness	5/45 (11.1%)	5
Musculoskeletal chest pain	1/45 (2.2%)	1
Musculoskeletal discomfort	1/45 (2.2%)	1
Myalgia	3/45 (6.7%)	4
Neck pain	3/45 (6.7%)	3
Pain in extremity	6/45 (13.3%)	9
Pain in jaw	2/45 (4.4%)	2
Tendonitis	1/45 (2.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour flare	29/45 (64.4%)	35
Nervous system disorders
Burning sensation	1/45 (2.2%)	1
Dementia	1/45 (2.2%)	1
Disturbance in attention	2/45 (4.4%)	3
Dizziness	16/45 (35.6%)	23
Headache	14/45 (31.1%)	17
Hypoaesthesia	5/45 (11.1%)	6
Lethargy	2/45 (4.4%)	2
Memory impairment	3/45 (6.7%)	3
Migraine with aura	1/45 (2.2%)	1
Neuropathy peripheral	12/45 (26.7%)	13
Paraesthesia	1/45 (2.2%)	1
Peripheral sensory neuropathy	1/45 (2.2%)	1
Post herpetic neuralgia	1/45 (2.2%)	1
Sinus headache	2/45 (4.4%)	2
Somnolence	1/45 (2.2%)	1
Syncope	1/45 (2.2%)	1
Tremor	2/45 (4.4%)	3
Psychiatric disorders
Agitation	1/45 (2.2%)	1
Anxiety	3/45 (6.7%)	3
Confusional state	2/45 (4.4%)	2
Depression	4/45 (8.9%)	5
Disorientation	1/45 (2.2%)	1
Hallucination	1/45 (2.2%)	1
Insomnia	9/45 (20%)	9
Mood altered	1/45 (2.2%)	1
Panic attack	1/45 (2.2%)	1
Psychotic disorder	1/45 (2.2%)	1
Restlessness	1/45 (2.2%)	1
Renal and urinary disorders
Dysuria	1/45 (2.2%)	1
Haematuria	2/45 (4.4%)	2
Haemorrhage urinary tract	1/45 (2.2%)	1
Nocturia	4/45 (8.9%)	4
Pollakiuria	1/45 (2.2%)	1
Renal failure	2/45 (4.4%)	2
Urethral pain	1/45 (2.2%)	1
Urethral spasm	1/45 (2.2%)	1
Urinary hesitation	1/45 (2.2%)	1
Urinary incontinence	1/45 (2.2%)	1
Urinary retention	2/45 (4.4%)	2
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/45 (2.2%)	1
Bronchiectasis	1/45 (2.2%)	1
Cough	19/45 (42.2%)	30
Dysphonia	4/45 (8.9%)	4
Dyspnoea	27/45 (60%)	34
Dyspnoea exertional	8/45 (17.8%)	8
Epistaxis	5/45 (11.1%)	6
Hyperventilation	1/45 (2.2%)	1
Hypopnoea	1/45 (2.2%)	1
Hypoxia	2/45 (4.4%)	3
Nasal congestion	9/45 (20%)	10
Nasal discomfort	2/45 (4.4%)	2
Nasal obstruction	1/45 (2.2%)	1
Oropharyngeal pain	10/45 (22.2%)	13
Pharyngeal oedema	1/45 (2.2%)	1
Pleural effusion	5/45 (11.1%)	5
Pleurisy	1/45 (2.2%)	1
Productive cough	9/45 (20%)	10
Pulmonary hypertension	1/45 (2.2%)	1
Rales	2/45 (4.4%)	2
Rhinorrhoea	8/45 (17.8%)	11
Rhonchi	1/45 (2.2%)	1
Sinus congestion	4/45 (8.9%)	4
Tonsillar inflammation	1/45 (2.2%)	2
Upper respiratory tract congestion	1/45 (2.2%)	1
Upper-airway cough syndrome	2/45 (4.4%)	2
Wheezing	5/45 (11.1%)	5
Skin and subcutaneous tissue disorders
Alopecia	1/45 (2.2%)	1
Blister	1/45 (2.2%)	1
Dry skin	10/45 (22.2%)	10
Erythema	3/45 (6.7%)	4
Hyperhidrosis	5/45 (11.1%)	5
Hypoaesthesia facial	1/45 (2.2%)	2
Nail discolouration	1/45 (2.2%)	1
Night sweats	12/45 (26.7%)	16
Pain of skin	1/45 (2.2%)	1
Petechiae	2/45 (4.4%)	2
Pruritus	13/45 (28.9%)	15
Pyoderma gangrenosum	1/45 (2.2%)	2
Rash	27/45 (60%)	40
Rash erythematous	1/45 (2.2%)	2
Rash generalised	2/45 (4.4%)	2
Rash pruritic	7/45 (15.6%)	8
Skin discolouration	1/45 (2.2%)	1
Skin hyperpigmentation	4/45 (8.9%)	4
Skin lesion	7/45 (15.6%)	8
Swelling face	1/45 (2.2%)	1
Urticaria	2/45 (4.4%)	2
Surgical and medical procedures
Glaucoma drug therapy	1/45 (2.2%)	1
Sinus operation	1/45 (2.2%)	1
Tooth repair	1/45 (2.2%)	1
Vascular disorders
Deep vein thrombosis	1/45 (2.2%)	1
Haematoma	1/45 (2.2%)	1
Hot flush	2/45 (4.4%)	2
Hypotension	4/45 (8.9%)	4
Lymphoedema	1/45 (2.2%)	1
Pallor	5/45 (11.1%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.