SCNSL1: High-Dose Sequential Chemoimmunotherapy for B-Cell Lymphomas With Central Nervous System Involvement

Sponsor

IRCCS San Raffaele (Other)

Overall Status

Unknown status

CT.gov ID

NCT00801216

Collaborator

Mundipharma K.K. (Industry)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
B-Cell Lymphomas	Drug: High-dose sequential chemotherapy and autologous transplant	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

38 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jan 1, 2007

Anticipated Primary Completion Date :

Jan 1, 2010

Anticipated Study Completion Date :

Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: High-dose sequential chemoimmunotherapy 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)	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) Other Names: Depocyte

Arm

Intervention/Treatment

Experimental: High-dose sequential chemoimmunotherapy

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)

Drug: High-dose sequential chemotherapy and autologous transplant

Other Names:

Depocyte

Outcome Measures

Primary Outcome Measures

Event-free survival [2-year]

Secondary Outcome Measures

Response duration [2-year]
Overall survival [2-year]
Tolerability [2-year]
Neurotoxicity [2-year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed diagnosis of diffuse large-cell, follicular or mantle cell lymphoma
CNS involvement (brain, meninges, cranial nerves, eyes, and/or spinal cord) at diagnosis or relapse after conventional chemotherapy
Diagnosis of CNS involvement either by brain biopsy or CSF cytology examination. Neuroimaging alone is acceptable only when stereotactic biopsy is formally contraindicated.
Age 19-65 years
ECOG performance status 0-3
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)
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)
Absence of HIV infection
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
Absence of any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Female patients must be non-pregnant and non-lactating. Sexually active patients of childbearing potential must implement adequate contraceptive measures during study participation
No treatment with other experimental drugs within the 6 weeks previous to enrolment
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