Clinical trial NCT00801216: High-dose Sequential Chemoimmunotherapy for B-cell Lymphomas With Central Nervous System Involvement
Official title: High-dose Sequential Chemotherapy and Rituximab (R-HDS) in Patients With Systemic B-cell Lymphoma With Central Nervous System Involvement at Diagnosis or Relapse
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: B-cell Lymphomas
Keywords: B-cell lymphomas
lymphomatous meningitis
liposomal cytarabine
autologous transplant
CNS involvement
Secondary CNS lymphomas
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
Collaborators: name: Mundipharma Pte Ltd.
First posted: 2008-12-03
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This prospective trial will assess the activity and feasibility of a new high-dose methotrexate-based high-dose sequential chemotherapy combination in patients with B-cell lymphomas and CNS involvement at diagnosis or relapse. Selected drugs, with a well-documented anti-lymphoma activity, will be administered at high doses to increase blood-brain barrier penetration and CNS bioavailability as well as to reduce potential cross-resistance.

Detailed description: Patients with aggressive B-cell lymphoma and involvement of the central nervous system at diagnosis or relapse will be treated with a combination of high-dose methotrexate and high-dose cytarabine, rituximab, and intrathecal depocyte followed by rituximab-high-dose sequential chemotherapy supported by autologous tsem cell transplantation.

Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed diagnosis of diffuse large-cell, follicular or mantle cell lymphoma
2. CNS involvement (brain, meninges, cranial nerves, eyes, and/or spinal cord) at diagnosis or relapse after conventional chemotherapy
3. Diagnosis of CNS involvement either by brain biopsy or CSF cytology examination. Neuroimaging alone is acceptable only when stereotactic biopsy is formally contraindicated.
4. Age 18-70 years
5. ECOG performance status 0-3
6. Adequate bone marrow (PLT \> 100000 mm3, Hb \> 9 g/dl, ANC \> 2.000 mm3), renal (creatinine clearance \> 60 mL/min), cardiac (VEF \> 50%), and hepatic function (total serum bilirubin \< 3 mg/dL, AST/ALT and gammaGT \< 2.5 per upper normal limit value), within 1 week prior to study start (unless the abnormality is due to lymphoma involvement)
7. Absence of symptomatic coronary artery disease, cardiac arrhythmias not well controlled with medication or myocardial infarction within the last 6 months (New York Heart Association Class III or IV heart disease)
8. Absence of HIV infection
9. No previous or concurrent malignancies with the exception of surgically cured carcinoma in-situ of the cervix and carcinoma of the skin and of other cancers without evidence of disease at least from 5 years
10. Absence of any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
11. Female patients must be non-pregnant and non-lactating. Sexually active patients of childbearing potential must implement adequate contraceptive measures during study participation
12. No treatment with other experimental drugs within the 6 weeks previous to enrolment
13. Give written informed consent prior to any study specific procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice

Exclusion Criteria:

* NA

Primary outcomes:
measure: Event-free Survival
timeFrame: 2-year
Secondary outcomes:
measure: Time to Progression (TTP)
timeFrame: 2-year
measure: Overall Survival
timeFrame: 5 Years
measure: Tolerability OF THE TREATMENT
timeFrame: 2-year
measure: Neurotoxicity
timeFrame: 2-year
Other outcomes:
Locations:
city: Milan
country: Italy
facility: San Raffaele Scientific Institute
Study officials:
affiliation: San Raffaele Scientific Institute
name: Andrés J. Ferreri, MD
role: STUDY_CHAIR
References:
citation: Ferreri AJ, Donadoni G, Cabras MG, Patti C, Mian M, Zambello R, Tarella C, Di Nicola M, D'Arco AM, Doa G, Bruno-Ventre M, Assanelli A, Foppoli M, Citterio G, Fanni A, Mule A, Caligaris-Cappio F, Ciceri F. High Doses of Antimetabolites Followed by High-Dose Sequential Chemoimmunotherapy and Autologous Stem-Cell Transplantation in Patients With Systemic B-Cell Lymphoma and Secondary CNS Involvement: Final Results of a Multicenter Phase II Trial. J Clin Oncol. 2015 Nov 20;33(33):3903-10. doi: 10.1200/JCO.2015.61.1236. Epub 2015 Aug 17.