CaLLypso: A Study of Rituximab (MabThera) in Combination With Chemotherapy in Participants With CD20-Positive B-Cell Chronic Lymphocytic Leukemia

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01609023
• Collaborator: (none)
• Enrollment: 67
• Locations: 9
• Duration (Months): 43
• Patients Per Site: 7.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This observational study will evaluate the safety and efficacy of rituximab in combination with chemotherapy in first- and second-line treatment of participants with cluster of differentiation 20 (CD20)-positive B-cell chronic lymphocytic leukemia. Data will be collected from eligible participants receiving rituximab according to the Summary of Product Characteristics (SPC) during 6 months of treatment.

Condition or Disease	Intervention/Treatment	Phase
Lymphocytic Leukemia, Chronic	Drug: Rituximab

Study Design

• Study Type: Observational
• Actual Enrollment: 67 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: A Non-Interventional, Observational Phase IV Study to Evaluate Safety of Rituximab (Mabthera®) in Combination With Chemotherapy in Patients Treated With CD20+ Β Chronic Lymphocytic Leukemia
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Rituximab Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to SPC and routine clinical practice will be observed for 24 months.	Drug: Rituximab; Rituximab will be administered in combination with chemotherapy according to SPC and routine clinical practice.; Other Names: MabThera

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Adverse Events (AEs) [Baseline up to 24 months]

   An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

Secondary Outcome Measures

1. Progression-Free Survival (PFS) Assessed Using Local Standards [From enrollment until disease progression or death, assessed up to 24 months]

   PFS was defined as the time from enrollment to the first documented progression of disease or death due to any cause. Progressive disease (PD) was defined as at least a 20 percent (%) increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. KaplanMeier estimate was used for analysis.

2. Percentage of Participants With Disease Progression or Death Assessed Using Local Standards [Months 6, 12, 18, and 24]

   PD was defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

3. Percentage of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) Assessed Using Local Standards [Months 6, 12, 18, and 24]

   Percentage of participants with CR or PR as determined by the investigator was reported. CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.

4. Percentage of Participants With CR Assessed Using Local Standards [Months 6, 12, 18, and 24]

   Percentage of participants with CR as determined by the investigator was reported. CR was defined as disappearance of all target lesions.

5. Percentage of Participants With PR Assessed Using Local Standards [Months 6, 12, 18, and 24]

   Percentage of participants with PR as determined by the investigator was reported. PR was defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.

6. Time to Progression (TTP) Assessed Using Local Standards [From enrollment until disease progression or death, assessed up to 26 months]

   TTP is defined as the time from enrollment to the PD. PD was defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Kaplan-Meier estimate was used for analysis.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Participants with CD20-positive B-cell chronic lymphocytic leukemia eligible for first-line or second-line therapy according to the approved SPC

Exclusion Criteria:

• Contraindications to rituximab therapy according to the approved SPC

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University General Hospital of Alexandroupolis; Haemotology	Alexandroupolis		Greece	68100
2	General Hospital of Athens Evangelismos; Hematology	Athens		Greece	106 76
3	Laiko General Hospital of Athens; A Propedeutical Clinic of Internal Medicine	Athens		Greece	115 27
4	Metropolitan Hospital; Hematology Dept	Athens		Greece	18547
5	Periph. University General Hospital of Heraklion; Hematology	Heraklion		Greece	711 10
6	University Hospital of Larissa; Hematology Dept.	Larissa		Greece	41110
7	University Hospital Of Patras; Dept. Of Internal Medicine-Hematology Division	Patras		Greece	265 00
8	General Hospital of Patras Agios Andreas; Hematology Department	Patra		Greece	26335
9	Georgios Papanikolaou Hospital; Hematology Department	Thessaloniki		Greece	570 10

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01609023
• Other Study ID Numbers: ML22235
• First Posted: May 31, 2012
• Last Update Posted: Jun 26, 2018
• Last Verified: Apr 1, 2018

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

Study Results

Participant Flow

Arm/Group Title	Rituximab
Arm/Group Description	Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Period Title: Overall Study
STARTED	67
COMPLETED	34
NOT COMPLETED	33

Baseline Characteristics

Arm/Group Title	Rituximab
Arm/Group Description	Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Overall Participants	67
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.12 (10.08)
Sex: Female, Male (Count of Participants)
Female	25 37.3%
Male	42 62.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Adverse Events (AEs)
Description	An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Time Frame	Baseline up to 24 months

Outcome Measure Data

Analysis Population Description

Safety population included all eligible participants.

Arm/Group Title	Rituximab
Arm/Group Description	Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Measure Participants	67
Number [percentage of participants]	89.6 133.7%

2. Secondary Outcome

Title	Progression-Free Survival (PFS) Assessed Using Local Standards
Description	PFS was defined as the time from enrollment to the first documented progression of disease or death due to any cause. Progressive disease (PD) was defined as at least a 20 percent (%) increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. KaplanMeier estimate was used for analysis.
Time Frame	From enrollment until disease progression or death, assessed up to 24 months

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Rituximab
Arm/Group Description	Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Measure Participants	67
Median (95% Confidence Interval) [months]	NA

3. Secondary Outcome

Title	Percentage of Participants With Disease Progression or Death Assessed Using Local Standards
Description	PD was defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time Frame	Months 6, 12, 18, and 24

Outcome Measure Data

Analysis Population Description

ITT population. Here, 'Overall Number of Participants Analyzed' = number of participants who were evaluable for this outcome. 'Number Analyzed' = participants who were evaluable for specified timepoints.

Arm/Group Title	Rituximab
Arm/Group Description	Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Measure Participants	67
Month 6	5.8 8.7%
Month 12	11.1 16.6%
Month 18	17.5 26.1%
Month 24	14.7 21.9%

4. Secondary Outcome

Title	Percentage of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) Assessed Using Local Standards
Description	Percentage of participants with CR or PR as determined by the investigator was reported. CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.
Time Frame	Months 6, 12, 18, and 24

Outcome Measure Data

Analysis Population Description

ITT population. Here, 'Overall Number of Participants Analyzed' = number of participants who were evaluable for this outcome. 'Number Analyzed' = participants who were evaluable for specified timepoints.

Arm/Group Title	Rituximab
Arm/Group Description	Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Measure Participants	67
Month 6	84 125.4%
Month 12	72.1 107.6%
Month 18	58.5 87.3%
Month 24	67.6 100.9%

5. Secondary Outcome

Title	Percentage of Participants With CR Assessed Using Local Standards
Description	Percentage of participants with CR as determined by the investigator was reported. CR was defined as disappearance of all target lesions.
Time Frame	Months 6, 12, 18, and 24

Outcome Measure Data

Analysis Population Description

ITT population. Here, 'Overall Number of Participants Analyzed' = number of participants who were evaluable for this outcome. 'Number Analyzed' = participants who were evaluable for specified timepoints.

Arm/Group Title	Rituximab
Arm/Group Description	Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Measure Participants	67
Month 6	42 62.7%
Month 12	41.8 62.4%
Month 18	37.5 56%
Month 24	44.1 65.8%

6. Secondary Outcome

Title	Percentage of Participants With PR Assessed Using Local Standards
Description	Percentage of participants with PR as determined by the investigator was reported. PR was defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.
Time Frame	Months 6, 12, 18, and 24

Outcome Measure Data

Analysis Population Description

ITT population. Here, 'Overall Number of Participants Analyzed' = number of participants who were evaluable for this outcome. 'Number Analyzed' = participants who were evaluable for specified timepoints.

Arm/Group Title	Rituximab
Arm/Group Description	Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Measure Participants	67
Month 6	42 62.7%
Month 12	30.2 45.1%
Month 18	22.5 33.6%
Month 24	23.5 35.1%

7. Secondary Outcome

Title	Time to Progression (TTP) Assessed Using Local Standards
Description	TTP is defined as the time from enrollment to the PD. PD was defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Kaplan-Meier estimate was used for analysis.
Time Frame	From enrollment until disease progression or death, assessed up to 26 months

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Rituximab
Arm/Group Description	Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Measure Participants	67
Mean (95% Confidence Interval) [months]	NA

Adverse Events

Time Frame	Baseline up to 24 months
Adverse Event Reporting Description	Safety population
Arm/Group Title	Rituximab
Arm/Group Description	Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
All Cause Mortality
	Rituximab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Rituximab
	Affected / at Risk (%)	# Events
Total	33/67 (49.3%)
Blood and lymphatic system disorders
Anaemia	3/67 (4.5%)
Eosinophilia	1/67 (1.5%)
Febrile neutropenia	5/67 (7.5%)
Leukopenia	1/67 (1.5%)
Neutropenia	10/67 (14.9%)
Thrombocytopenia	3/67 (4.5%)
General disorders
Asthenia	1/67 (1.5%)
Chest pain	1/67 (1.5%)
Death	1/67 (1.5%)
Disease progression	1/67 (1.5%)
Pyrexia	3/67 (4.5%)
Hepatobiliary disorders
Drug-induced liver injury	1/67 (1.5%)
Immune system disorders
Hypersensitivity	1/67 (1.5%)
Infections and infestations
Bronchitis	1/67 (1.5%)
Herpes zoster	2/67 (3%)
Infection	1/67 (1.5%)
Lung infection	1/67 (1.5%)
Pneumonia	1/67 (1.5%)
Respiratory tract infection	4/67 (6%)
Sinusitis	1/67 (1.5%)
Upper respiratory tract infection	2/67 (3%)
Injury, poisoning and procedural complications
Femur fracture	1/67 (1.5%)
Rib fracture	1/67 (1.5%)
Investigations
Blood creatinine increased	1/67 (1.5%)
Haemoglobin decreased	1/67 (1.5%)
Liver function test abnormal	1/67 (1.5%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/67 (1.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant	1/67 (1.5%)
Chronic lymphocytic leukaemia	1/67 (1.5%)
Nervous system disorders
Dizziness	1/67 (1.5%)
Memory impairment	1/67 (1.5%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/67 (1.5%)
Surgical and medical procedures
Spinal operation	1/67 (1.5%)
Other (Not Including Serious) Adverse Events
	Rituximab
	Affected / at Risk (%)	# Events
Total	47/67 (70.1%)
Blood and lymphatic system disorders
Anaemia	10/67 (14.9%)
Leukopenia	7/67 (10.4%)
Neutropenia	34/67 (50.7%)
Thrombocytopenia	12/67 (17.9%)
Gastrointestinal disorders
Vomiting	5/67 (7.5%)
General disorders
Chills	7/67 (10.4%)
Pyrexia	13/67 (19.4%)
Infections and infestations
Respiratory tract infection	4/67 (6%)
Vascular disorders
Hypertension	4/67 (6%)

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.