CHAIROS Study A Study of MabThera/Rituxan (Rituximab) Maintenance Therapy in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL) Naive to Chemotherapy

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02013817
• Collaborator: (none)
• Enrollment: 43
• Locations: 8
• Arm: 1
• Actual Duration (Months): 83.4
• Patients Per Site: 5.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of intense combination treatment including MabThera/Rituxan (rituximab), followed by MabThera/Rituxan maintenance therapy in patients with B-cell CLL who are naive to chemotherapy. The anticipated time on study treatment is 2.5 years.

Condition or Disease	Intervention/Treatment	Phase
Lymphocytic Leukemia, Chronic	Drug: rituximab [MabThera/Rituxan]; Drug: fludarabine; Drug: cyclophosphamide	Phase 2

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: CHAIROS - Effect of Early Brief Intensification by Chemoimmunotherapy With FCR Followed by FR and Rituximab Maintenance on Clinical Response in Chemo-naïve Patients With B-CLL
• Actual Study Start Date: Oct 11, 2005
• Actual Primary Completion Date: Sep 24, 2012
• Actual Study Completion Date: Sep 24, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MabThera/Rituxan	Drug: rituximab [MabThera/Rituxan]; Every 4 weeks for 6 cycles of induction, followed by maintenance therapy every 3 months x 8; Drug: fludarabine; Every 4 weeks, 6 cycles; Drug: cyclophosphamide; Every 4 weeks, 3 cycles

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Best Clinical Response of Clinical Remission (CR) [Weeks 1, 5, 9, 12, 13, 17, 21 and 24]

   Best clinical response was determined according to the National Cancer Institute (NCI) Clinical and Clinical plus (+) Radiological evaluations by central response assessment. Assessment of response was performed according to the NCI revised guidelines for the diagnosis and treatment of chronic lymphocytic lymphoma (CLL) with additional computerized tomography (CT) scan evaluation of lymphadenopathy. Per NCI guidelines, CR requires all of the following criteria at least 2 months after the last treatment: no lymphadenopathy (Ly)/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils greater than (>)1500 per microliter (/µL), platelets (PL) >100,000/µL, hemoglobin (Hb) >11.0 grams per deciliter (g/dL), lymphocytes (LC) (less than) <4000/µL, bone marrow (BM) sample must be normocellular for age, <30% LC.

Secondary Outcome Measures

1. Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) [Weeks 12 and 24 and at Final Staging (Week 4 after last maintenance dose)]

   Best clinical response was determined according to the NCI clinical evaluation and through radiological assessment. CR, CRi, CRu, partial remission (PR), partial remission with toxicity associated (PRTox), progressive disease (PD), and stable disease (SD) were evaluated. Assessment of response was performed according to the NCI revised guidelines for the diagnosis and treatment of CLL with additional CT scan evaluation of lymphadenopathy during the treatment period (Radiological). Response assessment for interim (Week 12), end of induction (Week 24) and at Final Staging (4 weeks after last maintenance dose). Last observation carried forward (LOCF) method was used for missing data. Percentages are based on the number of nonmissing observations within each stratum.

2. Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) [Weeks 12 and 24 and at Final Staging (Week 4 after last maintenance dose)]

   Best clinical response was determined according to the NCI clinical evaluation and through radiological assessment. CR, CRi, CRu, PR, PRTox, PD, and SD were evaluated. Assessment of response was performed according to the NCI revised guidelines for the diagnosis and treatment of CLL with additional CT scan evaluation of lymphadenopathy during the treatment period (Radiological). Response assessment for interim (Week 12), end of induction (Week 24) and at Final Staging (4 weeks after last maintenance dose). LOCF method was used for missing data. Percentages are based on the number of nonmissing observations within each stratum.

3. Time to Next Treatment - Percentage of Participants With an Event [Weeks 1, 5, 9, 12, 13, 17, 21 and 24 and every 8 weeks for 64 Weeks and every 6 months]

   Time to next treatment was calculated as the number of days from either discontinuation of the study drug or the administration of the last dose, until the participants needed next treatment.

4. Time to Next Treatment - Time to Event [Weeks 1, 5, 9, 12, 13, 17, 21 and 24 and every 8 weeks for 64 Weeks and every 6 months]

   Time to next treatment was calculated as the number of days from either discontinuation of the study drug or the administration of the last dose, until the participants needed next treatment.

5. Percentage of Participants With Adverse Events (AEs) [Day 1 of Cycles 1, 2, 3, 4, 5, and 6 to 28 days after the last trial medication.]

   AEs were recorded from the date of first medication administration until 28 days after the last trial medication.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Adult patients, >/= 18 years of age

• B-cell CLL

• No previous chemotherapy, radiotherapy, or immunotherapy

Exclusion Criteria:

• Reduced organ function, or bone marrow dysfunction not due to CLL

• Patients with a history of other malignancies within 2 years prior to study entry, except for adequately treated cancer in situ of the cervix, or basal or squamous cell skin cancer

• Patients with a history of severe cardiac disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tiroler Landeskrankenanstalten Ges.M.B.H.; Innere Medizin Abt. Für Hämatologie & Onkologie	Innsbruck		Austria	6020
2	LKH Hochsteiermark; Abt. für Innere Medizin	Leoben		Austria	8700
3	Kh Der Barmherzigen Schwestern; Interne I X	Linz		Austria	4010
4	A.Ö. Krankenhaus Der Elisabethinen Linz; I. Interne Abt.	Linz		Austria	4020
5	Kepler Universitätskliniken GmbH - Med Campus III; I. Medizinische Abteilung	Linz		Austria	4020
6	Landeskrankenhaus Rankweil; Interne E	Rankweil		Austria	6830
7	Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.	Salzburg		Austria	5020
8	Klinikum Kreuzschwestern Wels; Iii. Interne Abt.	Wels		Austria	4600

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Chair: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02013817
• Other Study ID Numbers: ML18434
• First Posted: Dec 17, 2013
• Last Update Posted: Aug 18, 2017
• Last Verified: Jul 1, 2017

• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Cyclophosphamide; Rituximab; Fludarabine

Study Results

Participant Flow

Arm/Group Title	Rituximab, Fludarabine, Cyclophosphamide
Arm/Group Description	Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 milligrams per square meter (mg/m^2) intravenously (IV) and cyclophosphamide 250 mg/m^2 IV on Days 1-3 and rituximab 375 mg/m^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m^2 IV on Day 1 and fludarabine 25 mg/m^2 IV and cyclophosphamide 250 mg/m^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m^2 IV on Day 1 and fludarabine 25 mg/m^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Period Title: Overall Study
STARTED	43
COMPLETED	16
NOT COMPLETED	27

Baseline Characteristics

Arm/Group Title	Rituximab, Fludarabine, Cyclophosphamide
Arm/Group Description	Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 mg/m^2 IV and cyclophosphamide 250 mg/m^2 IV on Days 1-3 and rituximab 375 mg/m^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m^2 IV on Day 1 and fludarabine 25 mg/m^2 IV and cyclophosphamide 250 mg/m^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m^2 IV on Day 1 and fludarabine 25 mg/m^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Overall Participants	43
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.0 (10.1)
Sex: Female, Male (Count of Participants)
Female	14 32.6%
Male	29 67.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Best Clinical Response of Clinical Remission (CR)
Description	Best clinical response was determined according to the National Cancer Institute (NCI) Clinical and Clinical plus (+) Radiological evaluations by central response assessment. Assessment of response was performed according to the NCI revised guidelines for the diagnosis and treatment of chronic lymphocytic lymphoma (CLL) with additional computerized tomography (CT) scan evaluation of lymphadenopathy. Per NCI guidelines, CR requires all of the following criteria at least 2 months after the last treatment: no lymphadenopathy (Ly)/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils greater than (>)1500 per microliter (/µL), platelets (PL) >100,000/µL, hemoglobin (Hb) >11.0 grams per deciliter (g/dL), lymphocytes (LC) (less than) <4000/µL, bone marrow (BM) sample must be normocellular for age, <30% LC.
Time Frame	Weeks 1, 5, 9, 12, 13, 17, 21 and 24

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Rituximab, Fludarabine, Cyclophosphamide
Arm/Group Description	Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 mg/m^2 IV and cyclophosphamide 250 mg/m^2 IV on Days 1-3 and rituximab 375 mg/m^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m^2 IV on Day 1 and fludarabine 25 mg/m^2 IV and cyclophosphamide 250 mg/m^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m^2 IV on Day 1 and fludarabine 25 mg/m^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Measure Participants	38
NCI Clinical	73.7 171.4%
NCI Clinical (including CRu, CRi)	94.7 220.2%
NCI Clinical + Radiological	63.2 147%
NCI Clinical + Radiological (including CRu, CRi)	78.9 183.5%

2. Secondary Outcome

Title	Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment)
Description	Best clinical response was determined according to the NCI clinical evaluation and through radiological assessment. CR, CRi, CRu, partial remission (PR), partial remission with toxicity associated (PRTox), progressive disease (PD), and stable disease (SD) were evaluated. Assessment of response was performed according to the NCI revised guidelines for the diagnosis and treatment of CLL with additional CT scan evaluation of lymphadenopathy during the treatment period (Radiological). Response assessment for interim (Week 12), end of induction (Week 24) and at Final Staging (4 weeks after last maintenance dose). Last observation carried forward (LOCF) method was used for missing data. Percentages are based on the number of nonmissing observations within each stratum.
Time Frame	Weeks 12 and 24 and at Final Staging (Week 4 after last maintenance dose)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Rituximab, Fludarabine, Cyclophosphamide
Arm/Group Description	Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 mg/m^2 IV and cyclophosphamide 250 mg/m^2 IV on Days 1-3 and rituximab 375 mg/m^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m^2 IV on Day 1 and fludarabine 25 mg/m^2 IV and cyclophosphamide 250 mg/m^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m^2 IV on Day 1 and fludarabine 25 mg/m^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Measure Participants	43
CR, Week 12	41.9 97.4%
CRu, Week 12	16.3 37.9%
CRi, Week 12	16.3 37.9%
PR, Week 12	11.6 27%
PRTox, Week 12	2.3 5.3%
SD, Week 12	0.0 0%
PD, Week 12	0.0 0%
Not evaluable, Week 12	11.6 27%
CR, Week 24	30.2 70.2%
CRu, Week 24	11.6 27%
CRi, Week 24	37.2 86.5%
PR, Week 24	9.3 21.6%
PRTox, Week 24	0.0 0%
SD, Week 24	0.0 0%
PD, Week 24	0.0 0%
Not evaluable, Week 24	11.6 27%
CR, Final staging	60.5 140.7%
CRu, Final staging	7.0 16.3%
CRi, Final staging	11.6 27%
PR, Final staging	7.0 16.3%
PRTox, Final staging	0.0 0%
SD, Final staging	0.0 0%
PD, Final staging	2.3 5.3%
Not evaluable, Final staging	11.6 27%

3. Secondary Outcome

Title	Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment)
Description	Best clinical response was determined according to the NCI clinical evaluation and through radiological assessment. CR, CRi, CRu, PR, PRTox, PD, and SD were evaluated. Assessment of response was performed according to the NCI revised guidelines for the diagnosis and treatment of CLL with additional CT scan evaluation of lymphadenopathy during the treatment period (Radiological). Response assessment for interim (Week 12), end of induction (Week 24) and at Final Staging (4 weeks after last maintenance dose). LOCF method was used for missing data. Percentages are based on the number of nonmissing observations within each stratum.
Time Frame	Weeks 12 and 24 and at Final Staging (Week 4 after last maintenance dose)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Rituximab, Fludarabine, Cyclophosphamide
Arm/Group Description	Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 mg/m^2 IV and cyclophosphamide 250 mg/m^2 IV on Days 1-3 and rituximab 375 mg/m^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m^2 IV on Day 1 and fludarabine 25 mg/m^2 IV and cyclophosphamide 250 mg/m^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m^2 IV on Day 1 and fludarabine 25 mg/m^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Measure Participants	43
CR, Week 12	30.2 70.2%
CRu, Week 12	4.7 10.9%
CRi, Week 12	7.0 16.3%
PR, Week 12	30.2 70.2%
PRTox, Week 12	9.3 21.6%
SD, Week 124	7.0 16.3%
PD, Week 12	0.0 0%
Not evaluable, Week 12	11.6 27%
CR, Week 24	23.3 54.2%
CRu, Week 24	7.0 16.3%
CRi, Week 24	30.2 70.2%
PR, Week 24	14.0 32.6%
PRTox, Week 24	7.0 16.3%
SD, Week 24	7.0 16.3%
PD, Week 24	0.0 0%
Not evaluable, Week 24	11.6 27%
CR, Final staging	48.8 113.5%
CRu, Final staging	7.0 16.3%
CRi, Final staging	7.0 16.3%
PR, Final staging	11.6 27%
PRTox, Final staging	2.3 5.3%
SD, Final staging	2.3 5.3%
PD, Final staging	9.3 21.6%
Not evaluable, Final staging	11.6 27%

4. Secondary Outcome

Title	Time to Next Treatment - Percentage of Participants With an Event
Description	Time to next treatment was calculated as the number of days from either discontinuation of the study drug or the administration of the last dose, until the participants needed next treatment.
Time Frame	Weeks 1, 5, 9, 12, 13, 17, 21 and 24 and every 8 weeks for 64 Weeks and every 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab, Fludarabine, Cyclophosphamide
Arm/Group Description	Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 mg/m^2 IV and cyclophosphamide 250 mg/m^2 IV on Days 1-3 and rituximab 375 mg/m^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m^2 IV on Day 1 and fludarabine 25 mg/m^2 IV and cyclophosphamide 250 mg/m^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m^2 IV on Day 1 and fludarabine 25 mg/m^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Measure Participants	43
Number [percentage of participants]	37.2 86.5%

5. Secondary Outcome

Title	Time to Next Treatment - Time to Event
Description	Time to next treatment was calculated as the number of days from either discontinuation of the study drug or the administration of the last dose, until the participants needed next treatment.
Time Frame	Weeks 1, 5, 9, 12, 13, 17, 21 and 24 and every 8 weeks for 64 Weeks and every 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab, Fludarabine, Cyclophosphamide
Arm/Group Description	Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 mg/m^2 IV and cyclophosphamide 250 mg/m^2 IV on Days 1-3 and rituximab 375 mg/m^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m^2 IV on Day 1 and fludarabine 25 mg/m^2 IV and cyclophosphamide 250 mg/m^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m^2 IV on Day 1 and fludarabine 25 mg/m^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Measure Participants	43
Mean (Standard Deviation) [days]	423.3 (398.5)

6. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs)
Description	AEs were recorded from the date of first medication administration until 28 days after the last trial medication.
Time Frame	Day 1 of Cycles 1, 2, 3, 4, 5, and 6 to 28 days after the last trial medication.

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Rituximab, Fludarabine, Cyclophosphamide
Arm/Group Description	Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 mg/m^2 IV and cyclophosphamide 250 mg/m^2 IV on Days 1-3 and rituximab 375 mg/m^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m^2 IV on Day 1 and fludarabine 25 mg/m^2 IV and cyclophosphamide 250 mg/m^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m^2 IV on Day 1 and fludarabine 25 mg/m^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Measure Participants	43
Any AE	100 232.6%
Related AE	93.0 216.3%
Severe AE	76.7 178.4%
SAE	62.8 146%
Pregnancy	0.0 0%

Adverse Events

Time Frame	Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication.
Adverse Event Reporting Description	Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Arm/Group Title	Rituximab, Fludarabine, Cyclophosphamide
Arm/Group Description	Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 mg/m^2 IV and cyclophosphamide 250 mg/m^2 IV on Days 1-3 and rituximab 375 mg/m^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m^2 IV on Day 1 and fludarabine 25 mg/m^2 IV and cyclophosphamide 250 mg/m^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m^2 IV on Day 1 and fludarabine 25 mg/m^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
All Cause Mortality
	Rituximab, Fludarabine, Cyclophosphamide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Rituximab, Fludarabine, Cyclophosphamide
	Affected / at Risk (%)	# Events
Total	30/43 (69.8%)
Blood and lymphatic system disorders
Leukopenia	2/43 (4.7%)
Anaemia	1/43 (2.3%)
Febrile neutropenia	3/43 (7%)
Gastrointestinal disorders
Abdominal pain	1/43 (2.3%)
Aphthous stomatitis	1/43 (2.3%)
Colonic polyp	1/43 (2.3%)
Diarrhoea	1/43 (2.3%)
Stomatitis	1/43 (2.3%)
General disorders
Pyrexia	5/43 (11.6%)
Chest pain	2/43 (4.7%)
Drug intolerance	1/43 (2.3%)
General physical health deterioration	1/43 (2.3%)
Hepatobiliary disorders
Bile duct stone	1/43 (2.3%)
Immune system disorders
Anaphylactic reaction	1/43 (2.3%)
Infections and infestations
Bronchitis	1/43 (2.3%)
Cytomegalovirus infection	1/43 (2.3%)
Pharyngitis	1/43 (2.3%)
Pneumonia	2/43 (4.7%)
Pneumonia primary atypical	1/43 (2.3%)
Postoperative infection	1/43 (2.3%)
Psoas abscess	1/43 (2.3%)
Respiratory tract infection	1/43 (2.3%)
Urninary tract infection	1/43 (2.3%)
Viral infection	1/43 (2.3%)
Encephalitis herpes	1/43 (2.3%)
Febrile infection	1/43 (2.3%)
Sepsis	1/43 (2.3%)
Tuberculosis	1/43 (2.3%)
Injury, poisoning and procedural complications
Extradural haematoma	1/43 (2.3%)
Femoral neck fracture	1/43 (2.3%)
Skull fracture	1/43 (2.3%)
Investigations
Ateriogram coronary	1/43 (2.3%)
Metabolism and nutrition disorders
Hyperglycaemia	1/43 (2.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/43 (2.3%)
Back pain	1/43 (2.3%)
Osteitis	1/43 (2.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma	1/43 (2.3%)
Tumour lysis syndrome	1/43 (2.3%)
Myelodysplastic syndrome	1/43 (2.3%)
Nervous system disorders
Cerebrovascular accident	1/43 (2.3%)
Subarachnoid haemorrhage	1/43 (2.3%)
Renal and urinary disorders
Renal colic	1/43 (2.3%)
Urinary retention	1/43 (2.3%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm	1/43 (2.3%)
Skin and subcutaneous tissue disorders
Actinic keratosis	1/43 (2.3%)
Drug eruption	1/43 (2.3%)
Surgical and medical procedures
Cataract operation	1/43 (2.3%)
Prostatic operation	1/43 (2.3%)
Vascular disorders
Capillary leak syndrome	1/43 (2.3%)
Other (Not Including Serious) Adverse Events
	Rituximab, Fludarabine, Cyclophosphamide
	Affected / at Risk (%)	# Events
Total	36/43 (83.7%)
Blood and lymphatic system disorders
Leukopenia	20/43 (46.5%)
Neutropenia	23/43 (53.5%)
Thrombocytopenia	18/43 (41.9%)
Anaemia	13/43 (30.2%)
Lymphopenia	14/43 (32.6%)
Haemolysis	2/43 (4.7%)
Febrile neutropenia	2/43 (4.7%)
Pancytopenia	1/43 (2.3%)
Cardiac disorders
Angina pectoris	1/43 (2.3%)
Arteriosclerosis coronary artery	1/43 (2.3%)
Palpitations	1/43 (2.3%)
Ear and labyrinth disorders
Vertigo	2/43 (4.7%)
Hypoacusis	1/43 (2.3%)
Tinnitus	1/43 (2.3%)
Endocrine disorders
Hyperthyroidism	1/43 (2.3%)
Hypothyroidism	1/43 (2.3%)
Eye disorders
Visual acuity reduced	2/43 (4.7%)
Gastrointestinal disorders
Nausea	14/43 (32.6%)
Diarrhoea	10/43 (23.3%)
Abdominal pain	4/43 (9.3%)
Constipation	4/43 (9.3%)
Abdominal pain upper	3/43 (7%)
Vomiting	3/43 (7%)
Gastritis	2/43 (4.7%)
Abdominal distension	2/43 (4.7%)
Bowel movement irregularity	1/43 (2.3%)
Dyspepsia	1/43 (2.3%)
Flatulence	1/43 (2.3%)
Gastrooesophageal reflux disease	1/43 (2.3%)
Paraesthesia oral	1/43 (2.3%)
Proctalgia	1/43 (2.3%)
Subileus	1/43 (2.3%)
Abdominal discomfort	1/43 (2.3%)
General disorders
Pyrexia	7/43 (16.3%)
Fatigue	8/43 (18.6%)
Oedema peripheral	4/43 (9.3%)
Chest pain	1/43 (2.3%)
Chills	3/43 (7%)
Influenza like illness	3/43 (7%)
Pain	3/43 (7%)
Mucosal inflammation	1/43 (2.3%)
Oedema	1/43 (2.3%)
Hepatobiliary disorders
Hepatitis	1/43 (2.3%)
Hyperbilirubinaemia	1/43 (2.3%)
Immune system disorders
Drug hypersensitivity	1/43 (2.3%)
Food allergy	1/43 (2.3%)
Hypersensitivity	1/43 (2.3%)
Infections and infestations
Nasopharyngitis	8/43 (18.6%)
Rhinitis	6/43 (14%)
Urinary tract infection	4/43 (9.3%)
Influenza	4/43 (9.3%)
Herpes simplex	3/43 (7%)
Respiratory tract infection	2/43 (4.7%)
Sinusitis	3/43 (7%)
Fungal infection	2/43 (4.7%)
Infection	3/43 (7%)
Oral candidiasis	3/43 (7%)
Bronchitis bacterial	1/43 (2.3%)
Febrile infection	2/43 (4.7%)
Fungal rash	1/43 (2.3%)
Gastroenteritis	1/43 (2.3%)
Gastrointestinal infection	1/43 (2.3%)
Herpes virus infection	1/43 (2.3%)
Herpes zoster	2/43 (4.7%)
Laryngitis	1/43 (2.3%)
Localised infection	1/43 (2.3%)
Lymphangitis	1/43 (2.3%)
Omphalitis	1/43 (2.3%)
Oral fungal infection	1/43 (2.3%)
Perianal abscess	1/43 (2.3%)
Postoperative infection	1/43 (2.3%)
Tooth abscess	1/43 (2.3%)
Viral pharyngitis	1/43 (2.3%)
Bronchitis	1/43 (2.3%)
Pharyngitis	1/43 (2.3%)
Injury, poisoning and procedural complications
Neck injury	1/43 (2.3%)
Thermal burn	1/43 (2.3%)
Thoracic vertebral fracture	1/43 (2.3%)
Investigations
C-reactive protein increased	1/43 (2.3%)
Neutrophil count decreased	1/43 (2.3%)
Weight decreased	1/43 (2.3%)
White blood cell count decreased	1/43 (2.3%)
Metabolism and nutrition disorders
Hypokalaemia	2/43 (4.7%)
Anorexia	1/43 (2.3%)
Iron deficiency	2/43 (4.7%)
Lactose intolerance	1/43 (2.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/43 (7%)
Back pain	4/43 (9.3%)
Bone pain	4/43 (9.3%)
Musculoskeletal pain	3/43 (7%)
Neck pain	3/43 (7%)
Arthritis	2/43 (4.7%)
Muscle spasms	2/43 (4.7%)
Osteoporosis	2/43 (4.7%)
Pain in extremity	2/43 (4.7%)
Exostosis	1/43 (2.3%)
Intervertebral disc protrusion	1/43 (2.3%)
Myalgia	1/43 (2.3%)
Osteoarthritis	1/43 (2.3%)
Pain in jaw	1/43 (2.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma	1/43 (2.3%)
Neuroendocrine tumour	1/43 (2.3%)
Nervous system disorders
Dizziness	2/43 (4.7%)
Headache	2/43 (4.7%)
Sciatica	2/43 (4.7%)
Carotid artery stenosis	1/43 (2.3%)
Carpal tunnel syndrome	1/43 (2.3%)
Convulsions local	1/43 (2.3%)
Dysaesthesia	1/43 (2.3%)
Neuropathy	1/43 (2.3%)
Polyneuropathy	1/43 (2.3%)
Sensory loss	1/43 (2.3%)
Psychiatric disorders
Burnout syndrome	1/43 (2.3%)
Depression	1/43 (2.3%)
Renal and urinary disorders
Dysuria	1/43 (2.3%)
Renal pain	1/43 (2.3%)
Urinary tract pain	1/43 (2.3%)
Micturition disorder	1/43 (2.3%)
Reproductive system and breast disorders
Menopausal symptoms	1/43 (2.3%)
Oedema genital	1/43 (2.3%)
Testicular pain	1/43 (2.3%)
Respiratory, thoracic and mediastinal disorders
Cough	14/43 (32.6%)
Dyspnoea	2/43 (4.7%)
Pharyngolaryngeal pain	2/43 (4.7%)
Dysphonia	1/43 (2.3%)
Dysphonia exertional	1/43 (2.3%)
Lung disorder	1/43 (2.3%)
Skin and subcutaneous tissue disorders
Rash	7/43 (16.3%)
Actinic keratosis	1/43 (2.3%)
Hyperkeratosis	2/43 (4.7%)
Rash maculo-papular	2/43 (4.7%)
Rash pruritic	2/43 (4.7%)
Alopecia	1/43 (2.3%)
Dermatitis acneiform	1/43 (2.3%)
Eczema	1/43 (2.3%)
Erythema	1/43 (2.3%)
Night sweats	1/43 (2.3%)
Pemphigoid	1/43 (2.3%)
Subcutaneous nodule	1/43 (2.3%)
Urticaria	1/43 (2.3%)
Vascular disorders
Hypertension	3/43 (7%)
Circulatory collapse	1/43 (2.3%)
Hot flush	1/43 (2.3%)
Hypotension	1/43 (2.3%)
Vein pain	1/43 (2.3%)
Venous insufficiency	1/43 (2.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.