High-dose Sequential Chemoimmunotherapy for B-cell Lymphomas With Central Nervous System Involvement

Phase 2

Completed

• Conditions: B-cell Lymphomas
• Interventions: Drug: High-dose sequential chemotherapy and autologous transplant

• Registration Number: NCT00801216
• Lead Sponsor: Andrés José Maria Ferreri

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.

Study Timeline

• Study Start: 2007-01
• Study First Submitted: 2008-11-28
• Study First Submitted QC: 2008-12-02
• Study First Posted: 2008-12-03
• Primary Completion: 2013-01
• Study Completion: 2013-01
• Results First Submitted: 2023-03-13
• Status Verified: 2024-11
• Results First Submitted QC: 2024-11-22
• Last Update Submitted: 2024-11-22
• Results First Posted: 2024-12-10
• Last Update Posted: 2024-12-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
High-dose sequential chemoimmunotherapy	High-dose sequential chemotherapy and autologous transplant	Two courses of methotrexate 3.5 g/mq day 1 and cytarabine 2 g/mq twice a day, for two days, Rituximab 375 mg/mq days 3 \& 11 and Intrathecal liposomal cytarabine 50 mg day 6(Phase I) followed in case of response by cyclophosphamide 7 g/mq plus Rituximab 375 mg/mq and Intrathecal liposomal cytarabine 50 mg Leukapheresis A and cryopreservation (Phase II), Cytarabine 2 g/mq twice a day for 4 days, Rituximab 375 mg/m2 and Reinfusion of stem cells (Phase III), etoposide 2 g/mq, Intrathecal liposomal cytarabine 50 mg (Phase IV) and high-dose Thiotepa-BCNU supported by autologous stem cell transplant (Phase V), and whole-brain radiotherapy in patients who do not achieve a complete remission after chemotherapy (Phase VI)

Primary Outcome Measures

Name	Time	Method
Event-free Survival	2-year	No new pathological events in a 2 ys follow-up period

Secondary Outcome Measures

Name	Time	Method
Time to Progression (TTP)	2-year	Time elapsed from Lymphoma diagnosis and CNS involvement
Overall Survival	5 Years	Patients alive after 5 years long follow-up
Tolerability OF THE TREATMENT	2-year	For the 38 patients enrolled the number of chemotherapy administered / expected during treatment period
Neurotoxicity	2-year	Total number of patients with neurotoxic events during treatment

Trial Locations

Locations (1)

San Raffaele Scientific Institute; 🇮🇹 Milan, Italy