High-Dose Sequential Chemoimmunotherapy for B-Cell Lymphomas With Central Nervous System Involvement

B-Cell Lymphomas Clinical Trial

— SCNSL1  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00801216
• Other study ID #: SCNSL1
• Secondary ID: IIL-SCNSL-1
• Status: Recruiting
• Phase: Phase 2
• First received: November 28, 2008
• Last updated: December 2, 2008
• Start date: January 2007
• Est. completion date: January 2012

Study information

• Verified date: October 2008
• Source: IRCCS San Raffaele
• Contact: Andrés J. Ferreri, MD
• Phone: 0039-02-2643 7649
• Email: andres.ferreri[@]hsr.it
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationItaly: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 38
• Est. completion date: January 2012
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years to 65 Years

Eligibility

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 19-65 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:

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• B-Cell Lymphomas
• Lymphoma
• Lymphoma, B-Cell

Intervention

Drug:
• 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)

Locations

Country	Name	City	State
Italy	San Raffaele Scientific Institute	Milan
Italy	San Raffaele Scientific Institute	Milan

Sponsors (2)

Lead Sponsor	Collaborator
IRCCS San Raffaele	Mundipharma K.K.

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival		2-year	Yes
Secondary	Response duration		2-year	Yes
Secondary	Overall survival		2-year	Yes
Secondary	Tolerability		2-year	Yes
Secondary	Neurotoxicity		2-year	Yes