A Study of MabThera (Rituximab) in Primary Central Nervous System Lymphoma.

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00517699
• Collaborator: (none)
• Enrollment: 5
• Locations: 2
• Arm: 1
• Duration (Months): 18
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of MabThera plus high dose methotrexate plus high dose cytarabine in patients with central nervous system non-Hodgkin's lymphoma. Eligible patients will receive a treatment regimen consisting of MabThera (750mg/m2 iv) plus methotrexate (8g/m2 iv) given at intervals up to week 22, plus cytarabine (2g/m2 iv) at week 11 and week 22. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: rituximab [MabThera/Rituxan]; Drug: Methotrexate; Drug: Cytarabine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Study of the Effect of Rituxan, High Dose Methotrexate and High Dose Cytarabine on Response Rate in Patients With Primary Central Nervous System Lymphoma.
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: rituximab [MabThera/Rituxan]; 750mg/m2 iv; Drug: Methotrexate; 8g/m2 iv; Drug: Cytarabine; 2g/m2 iv

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Complete Response (CR) or Unconfirmed CR (CRu) [Week 24]

   CR: complete disappearance of all enhancing abnormalities on contrast-enhanced cranial magnetic resonance imaging (MRI); no evidence of active ocular lymphoma as defined by absence of cells in the vitreous and resolution of any previously documented retinal or optic nerve infiltrates; negative cerebrospinal fluid (CSF) cytology; at the time of CR determination, participant had discontinued use of all corticosteroids for at least 2 weeks. CRu requires fulfillment of CR criteria but with these limitations: Fulfills CR criteria but had continued requirement for corticosteroid therapy at any dose; small but persistent enhancing abnormality on MRI related to biopsy or focal hemorrhage; persistent minor abnormality on follow-up ophthalmologic exam (related to persistent non-malignant cells in vitreous, or alterations in retina/optic nerve not consistent with tumor infiltration) if the abnormality is unlikely to represent ocular lymphoma.

2. Percentage of Participants With a CR, CRu or Partial Response (PR) [Week 24]

   PR: greater than or equal to (≥) 50 percent (%) decrease in the contrast-enhancing lesion seen on MRI as compared with the baseline images; (2) Corticosteroid dose was irrelevant to the determination of PR; for participants with ocular disease, ophthalmologic exam must show a decrease in vitreous cell count or retina/optic nerve cellular infiltrate but may have continued to show persistent malignant or suspicious cells; for participants with CSF positive for neoplastic cells, CSF cytology may be negative or continue to show persistent malignant or suspicious cells in patients with ≥50% decrease in the primary brain lesions; no new sites of disease.

Secondary Outcome Measures

1. Percentage of Participants With Initial CR or CRu and Subsequent Disease Relapse [Week 24]

2. Overall Survival [Time of last follow-up assessment between Day 1 and 3 years]

   Time from entry into trial until death of any cause. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last dose and participants with no post baseline information were censored at the baseline date.

3. Progression-Free Survival (PFS) [Week 24]

   PFS was defined as the time interval between the entry into trial and occurrence of one of the following events: progression of disease (PD) or death as a result of primary central nervous system lymphoma (PCNSL). Participants who were withdrawn from the study without documented progression and for whom there existed case report form (CRF) evidence that evaluations had been made, were censored at the date of last tumor assessment when participant was known to be progression free. Participants without postbaseline tumor assessments but known to be alive were censored at the time of randomization. PD required a ≥25% increase in the contrast-enhanced lesion seen on MRI as compared with baseline or best response (comparison should be made to the smallest of multiple lesions); progression of ocular disease as indicated by an increase in vitreous cell count or progressive retinal or optic nerve infiltration, appearance of any new lesion or site of disease during or at the end of therapy.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• adult patients, 18-80 years of age;

• histological diagnosis of primary central nervous system lymphoma;

• B-cell proliferation verified by positive staining for CD20;

• =1 measurable lesion.

Exclusion Criteria:

• prior chemotherapy, other than corticosteroids, >=6 weeks before and after diagnosis or surgery;

• history of prior cranial irradiation;

• evidence of plurisystemic non-Hodgkin's lymphoma;

• other active malignant disease (other than basal cell or squamous cell cancer of skin,or cancer in situ of cervix;

• uncontrolled active infection.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Greenfield Park	Quebec	Canada	J4V 2H1
2		Quebec City	Quebec	Canada	G1J 1Z4

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: NCT00517699
• Other Study ID Numbers: ML19652
• First Posted: Aug 17, 2007
• Last Update Posted: Aug 8, 2014
• Last Verified: Jul 1, 2014

• Additional relevant MeSH terms: Lymphoma; Cytarabine; Rituximab; Methotrexate

Study Results

Participant Flow

Arm/Group Title	Rituximab, Cytarabine, and Methotrexate (MTX)
Arm/Group Description	Participants received single doses of rituximab 750 milligrams per square meter (mg/m^2) intravenously (IV) at Weeks 1 through 5, and 7, 9, 11, 14, 16, 18, 20, and 22; cytarabine 2 grams per square meter (g/m^2) IV every 24 hours for 2 doses at Weeks 11 and 22; and single doses of MTX 8 g/m^2 IV at Weeks 3, 5, 7, 9, 14, 16, 18, and 20.
Period Title: Overall Study
STARTED	5
COMPLETED	0
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Rituximab, Cytarabine, and MTX
Arm/Group Description	Participants received single doses of rituximab 750 mg/m^2 IV at Weeks 1 through 5, and 7, 9, 11, 14, 16, 18, 20, and 22; cytarabine 2 g/m^2 IV every 24 hours for 2 doses at Weeks 11 and 22; and single doses of MTX 8 g/m^2 IV at Weeks 3, 5, 7, 9, 14, 16, 18, and 20.
Overall Participants	5
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.8 (8.23)
Sex: Female, Male (Count of Participants)
Female	2 40%
Male	3 60%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Complete Response (CR) or Unconfirmed CR (CRu)
Description	CR: complete disappearance of all enhancing abnormalities on contrast-enhanced cranial magnetic resonance imaging (MRI); no evidence of active ocular lymphoma as defined by absence of cells in the vitreous and resolution of any previously documented retinal or optic nerve infiltrates; negative cerebrospinal fluid (CSF) cytology; at the time of CR determination, participant had discontinued use of all corticosteroids for at least 2 weeks. CRu requires fulfillment of CR criteria but with these limitations: Fulfills CR criteria but had continued requirement for corticosteroid therapy at any dose; small but persistent enhancing abnormality on MRI related to biopsy or focal hemorrhage; persistent minor abnormality on follow-up ophthalmologic exam (related to persistent non-malignant cells in vitreous, or alterations in retina/optic nerve not consistent with tumor infiltration) if the abnormality is unlikely to represent ocular lymphoma.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed.

Arm/Group Title	Rituximab, Cytarabine, and MTX
Arm/Group Description	Participants received single doses of rituximab 750 mg/m^2 IV at Weeks 1 through 5, and 7, 9, 11, 14, 16, 18, 20, and 22; cytarabine 2 g/m^2 IV every 24 hours for 2 doses at Weeks 11 and 22; and single doses of MTX 8 g/m^2 IV at Weeks 3, 5, 7, 9, 14, 16, 18, and 20.
Measure Participants	0

2. Primary Outcome

Title	Percentage of Participants With a CR, CRu or Partial Response (PR)
Description	PR: greater than or equal to (≥) 50 percent (%) decrease in the contrast-enhancing lesion seen on MRI as compared with the baseline images; (2) Corticosteroid dose was irrelevant to the determination of PR; for participants with ocular disease, ophthalmologic exam must show a decrease in vitreous cell count or retina/optic nerve cellular infiltrate but may have continued to show persistent malignant or suspicious cells; for participants with CSF positive for neoplastic cells, CSF cytology may be negative or continue to show persistent malignant or suspicious cells in patients with ≥50% decrease in the primary brain lesions; no new sites of disease.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed.

Arm/Group Title	Rituximab, Cytarabine, and MTX
Arm/Group Description	Participants received single doses of rituximab 750 mg/m^2 IV at Weeks 1 through 5, and 7, 9, 11, 14, 16, 18, 20, and 22; cytarabine 2 g/m^2 IV every 24 hours for 2 doses at Weeks 11 and 22; and single doses of MTX 8 g/m^2 IV at Weeks 3, 5, 7, 9, 14, 16, 18, and 20.
Measure Participants	0

3. Secondary Outcome

Title	Percentage of Participants With Initial CR or CRu and Subsequent Disease Relapse
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed.

Arm/Group Title	Rituximab, Cytarabine, and MTX
Arm/Group Description	Participants received single doses of rituximab 750 mg/m^2 IV at Weeks 1 through 5, and 7, 9, 11, 14, 16, 18, 20, and 22; cytarabine 2 g/m^2 IV every 24 hours for 2 doses at Weeks 11 and 22; and single doses of MTX 8 g/m^2 IV at Weeks 3, 5, 7, 9, 14, 16, 18, and 20.
Measure Participants	0

4. Secondary Outcome

Title	Overall Survival
Description	Time from entry into trial until death of any cause. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last dose and participants with no post baseline information were censored at the baseline date.
Time Frame	Time of last follow-up assessment between Day 1 and 3 years

Outcome Measure Data

Analysis Population Description

Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed.

Arm/Group Title	Rituximab, Cytarabine, and MTX
Arm/Group Description	Participants received single doses of rituximab 750 mg/m^2 IV at Weeks 1 through 5, and 7, 9, 11, 14, 16, 18, 20, and 22; cytarabine 2 g/m^2 IV every 24 hours for 2 doses at Weeks 11 and 22; and single doses of MTX 8 g/m^2 IV at Weeks 3, 5, 7, 9, 14, 16, 18, and 20.
Measure Participants	0

5. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS was defined as the time interval between the entry into trial and occurrence of one of the following events: progression of disease (PD) or death as a result of primary central nervous system lymphoma (PCNSL). Participants who were withdrawn from the study without documented progression and for whom there existed case report form (CRF) evidence that evaluations had been made, were censored at the date of last tumor assessment when participant was known to be progression free. Participants without postbaseline tumor assessments but known to be alive were censored at the time of randomization. PD required a ≥25% increase in the contrast-enhanced lesion seen on MRI as compared with baseline or best response (comparison should be made to the smallest of multiple lesions); progression of ocular disease as indicated by an increase in vitreous cell count or progressive retinal or optic nerve infiltration, appearance of any new lesion or site of disease during or at the end of therapy.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Due to early study termination, all efficacy data were documented by data listings only, no data analysis was performed.

Arm/Group Title	Rituximab, Cytarabine, and MTX
Arm/Group Description	Participants received single doses of rituximab 750 mg/m^2 IV at Weeks 1 through 5, and 7, 9, 11, 14, 16, 18, 20, and 22; cytarabine 2 g/m^2 IV every 24 hours for 2 doses at Weeks 11 and 22; and single doses of MTX 8 g/m^2 IV at Weeks 3, 5, 7, 9, 14, 16, 18, and 20.
Measure Participants	0

Adverse Events

Time Frame	Baseline up to 24 weeks.
Arm/Group Title	Rituximab, Cytarabine, and MTX
Arm/Group Description	Participants received single doses of rituximab 750 mg/m^2 IV at Weeks 1 through 5, and 7, 9, 11, 14, 16, 18, 20, and 22; cytarabine 2 g/m^2 IV every 24 hours for 2 doses at Weeks 11 and 22; and single doses of MTX 8 g/m^2 IV at Weeks 3, 5, 7, 9, 14, 16, 18, and 20.
All Cause Mortality
	Rituximab, Cytarabine, and MTX
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Rituximab, Cytarabine, and MTX
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Other (Not Including Serious) Adverse Events
	Rituximab, Cytarabine, and MTX
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Blood and lymphatic system disorders
Anaemia	1/5 (20%)
Leukopenia	1/5 (20%)
Neutropenia	4/5 (80%)
Thrombocytopenia	1/5 (20%)
Eye disorders
Eye allergy	1/5 (20%)
Gastrointestinal disorders
Abdominal pain	2/5 (40%)
Constipation	3/5 (60%)
Diarrhoea	1/5 (20%)
Dyspepsia	1/5 (20%)
Gingival pain	1/5 (20%)
Nausea	3/5 (60%)
Vomiting	2/5 (40%)
General disorders
Fatigue	3/5 (60%)
Generalised oedema	2/5 (40%)
Hyperthermia	3/5 (60%)
Injection site erythema	1/5 (20%)
Injection site pain	1/5 (20%)
Non-cardiac chest pain	1/5 (20%)
Oedema peripheral	3/5 (60%)
Pain	1/5 (20%)
Vessel puncture site bruise	1/5 (20%)
Hepatobiliary disorders
Hepatitis	1/5 (20%)
Infections and infestations
Conjunctivitis bacterial	1/5 (20%)
Herpes zoster	1/5 (20%)
Upper respiratory tract infection	2/5 (40%)
Urinary tract infection	1/5 (20%)
Injury, poisoning and procedural complications
Drug toxicity	3/5 (60%)
Skin laceration	1/5 (20%)
Wound	1/5 (20%)
Investigations
Creatinine renal clearance decreased	1/5 (20%)
Hepatic enzyme abnormal	1/5 (20%)
Hepatic enzyme increased	2/5 (40%)
Weight increased	1/5 (20%)
Metabolism and nutrition disorders
Decreased appetite	1/5 (20%)
Electrolyte imbalance	1/5 (20%)
Hypernatraemia	1/5 (20%)
Hypokalaemia	5/5 (100%)
Malnutrition	1/5 (20%)
Musculoskeletal and connective tissue disorders
Mobility decreased	1/5 (20%)
Muscular weakness	1/5 (20%)
Myalgia	1/5 (20%)
Nervous system disorders
Dementia	1/5 (20%)
Dysgeusia	1/5 (20%)
Headache	3/5 (60%)
Loss of consciousness	1/5 (20%)
Neurological symptom	1/5 (20%)
Somnolence	1/5 (20%)
Psychiatric disorders
Agitation	1/5 (20%)
Anxiety	2/5 (40%)
Confusional state	1/5 (20%)
Insomnia	1/5 (20%)
Mood altered	1/5 (20%)
Renal and urinary disorders
Renal cyst	1/5 (20%)
Renal failure	1/5 (20%)
Urinary incontinence	1/5 (20%)
Urinary retention	1/5 (20%)
Reproductive system and breast disorders
Erectile dysfunction	1/5 (20%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/5 (20%)
Pharyngolaryngeal pain	1/5 (20%)
Rales	1/5 (20%)
Respiratory distress	1/5 (20%)
Upper respiratory tract congestion	1/5 (20%)
Skin and subcutaneous tissue disorders
Dermatitis	1/5 (20%)
Dermatitis contact	1/5 (20%)
Erythema	2/5 (40%)
Hyperhidrosis	1/5 (20%)
Pruritus	1/5 (20%)
Rash	1/5 (20%)
Skin burning sensation	1/5 (20%)
Vascular disorders
Arterial thrombosis limb	1/5 (20%)
Flushing	1/5 (20%)
Hot flush	1/5 (20%)
Hypertension	2/5 (40%)
Hypotension	1/5 (20%)
Venous thrombosis limb	1/5 (20%)

Limitations/Caveats

The study was terminated early due to lack of enrollment.

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.